JPH03206042A - Hypotensor - Google Patents

Abstract

PURPOSE:To obtain a hypotensor having excellent potassium channel activation activity by using a specific thiazolo[5,4-b]azepine derivative as an active component. CONSTITUTION:The objective agent contains, as an active component, a compound of formula I (R<1> is H, aliphatic group, carboxylic acid acyl or sulfonic acid acyl each of which may have substituents; R<2> is H, aromatic group or aliphatic group each of which may have substituents) or its salt, e.g. 2-(4- chlorostyryl)-5,6,7,8-tetrahydro-4H-thiazolo[5,4-b]azepine. The compound is useful as a remedy for circulatory diseases of mammals such as hypertension or stenocardia. It is administered twice or thrice a day for adult preferably at a rate of 0.5-20mg per dose in the case of oral administration or 0.3-10mg per dose in the case of parenteral administration. The compound of formula I can be produced by reacting a compound of formula II with a reactive derivative of carboxylic acid of formula R<2>COX and treating the resultant compound of formula III with a sulfurizing agent.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to compounds useful as antihypertensive agents and antihypertensive agents.

Problems to be solved by conventional technology and inventions Potassium channel openers (potassium channel activators) in recent years
Compounds said to be antihypertensive (eg, BRL34915, pinacidil, nicorandil, etc.) are attracting attention as antihypertensive and antianginal drugs based on a new mechanism of action.

An object of the present invention is to provide an antihypertensive agent that has a novel structure completely different from the previously known potassium channel opener compounds described above and has an excellent potassium channel activating effect.

Means for Solving the Problems As a result of our diligent search for new antihypertensive agents, the present inventors discovered that
Thiazolo [5.4-
b] It was discovered that acepine derivatives or salts thereof have a strong antihypertensive effect, which is thought to be based on potassium channel activating effect, and after further studies, the present invention was completed.

That is, the present invention provides a hydrogen atom or an aliphatic group, a carboxylic acid acyl group, or a sulfonic acid acyl group, each of which may have a substituent, and R2 is a hydrogen atom or Each represents an aromatic ring group or an aliphatic group which may have a substituent. ] or a salt thereof.

Furthermore, among the compounds represented by formula [1], especially R
2 or Formula R7 "[In the formula, R5, Re and R7 are the same or different and each represents a hydrogen atom, a lower alkyl group, or an aromatic ring group which may have a substituent, and R5 and R7 each represent They may be combined to form a ring. However, at least one of R' and R' is an aromatic ring group which may have a substituent. ] (hereinafter referred to as compound [do]
) was found to have a strong antihypertensive effect.

In addition, in particular, in formula [11, R2 is of the formula CH=CH-R" [wherein R" is an aromatic ring group substituted with an amino group or a substituted amino group, and is in cis coordination with respect to the thiazoloazepine ring. A compound which is a group represented by [I”]
) is preferred.

In the general formula [I], the aliphatic group represented by R1 may be a saturated group or an unsaturated group, and examples thereof include an alkyl group, an alkenyl group, and an alkynyl group. . The alkyl group may be linear, branched or cyclic. Among these alkyl groups, carbon number 1 to 6
Preferred are lower alkyl groups such as methyl, ethyl, propyl i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl. Examples include cyclobutyl and cyclopentyl. Also, is it represented by R1? The alkenyl group generally has 1.2 to 6 carbon atoms.
are preferred, such as vinyl, allyl, propenyl, i-probenyl, 2-butenyl, 2,4-butadienyl, 1,:3-butadienyl, 2-pentenyl, 2,
Examples include 4-pentadienyl. The alkynyl group represented by R1 is generally preferably a group having 2 to 6 carbon atoms, such as ethynyl, 2-furopynyl, and the like. The substituent that these aliphatic groups may have may be any substituent, but any substituent that is commonly used in medicine may be used. Specifically, for example, hydroxyl + CI-3 alkoxy 7. For example, methoxy, etquin,
n-proboxy/or iso-propoxy, etc. (as in methoxymethyl or l-ethynethyl, etc.); aryloxy, such as phenoxy; C7■.

Aralkoxy, such as mercapto; Cl-3 alkylthio, such as methylthio or ethylthio; arylthio. C7. Aralkylthio, amino (e.g. < in 2-aminoethyl); C
+-: +alkyl? substituted mono- or di-substituted amino,
such as methylamino, ethylamino or dimethylamino; halogens, such as chloro or bromo (such as in dibromoethyl); esterification compounds, such as C t-S alkoxycarbonyl (such as methoxycarbonyl or ethoxycarbonyl); or penzyloxycarbonyl; C2-4alcoquinyloxy; formyl: Ct-+Oacyl such as acetyl, probionyl or penzoyl; C2■.

Acyloxy, e.g. acetoxy, propionyloxy/
or pivaloyloxy; cyano; phthalimide:
C t-1. Ashi. Cz-s alkoxycarbonylamino, such as methoxycarbonylamino or ethoxycarbonylamino; or C7-10 aralkoxycarbonylamino, such as penzyloxycarbonylamino,
Cyclic amine 7 group (e.g. pyrrolidino, morphol 7, etc.),
Examples thereof include a carboxyl group, a carbamoyl group (the group consisting of these groups is hereinafter referred to as group A), and the like.

Among these group A, carboxyl groups, esterified carboxyl groups, carbamoyl groups, mono- or di(C + -3 alkyl) amine 7 groups, etc. are particularly preferred. R
Examples of the sulfonic acid acyl group represented by l include alkylsulfonyl groups preferably having 1 to 3 carbon atoms, such as methanesulfonyl, ethanesulfonyl, and propanesulfonyl, and phenylsulfonyl groups. Among these, the alkylsulfonyl group may have a substituent remaining from Group A above, for example. Among these substituents, mono- or di-substituted amino substituted with C1-3 alkyl such as dimethylamino and diethylamino is particularly preferred.

When the phenylsulfonyl group represented by R1 has a substituent on the phenyl ring, examples of the substituent include halogen, nitro, amino (1 to 2 C, 1.alkyl, C,, alkenyl+C3- IIcyclo7ru4-
or phenyl as a substituent. ). Sulfo, mercabuto, hydroxy, sulfoquine, sulfamoyl, C11 alkyl (amino, diC, -37lkylami/.monoC I-ff having 1 to 3 substituents of alkylamino, halogen, hydroxy, cyano, carboxy) (also good), C, one. Alkoxy (C,
-37 alkylthio may have 1 to 3 substituents), penzyloxy+ C I-3 alkylthio+
CI-37 Rukylsulfonamide, amidino (CI-3
(optionally substituted with alwyl, benzyl), C
+-s alkoxyformimidoyl, methylenedioxy, C, -, alkylsulfonyl r C I-3 alkylsulfonylamino, esterified carboxy, e.g.
-47 alkoxycarbonyl (such as methoxycarbonyl or ethoxycarbonyl), or pendyloxycarbonyl; C, -4 alkoxycarbonyloxy; formyl: Cl-I. Acyl such as acetyl, ropionyl or benzoyl; C, 1,. Acyloxy, such as acetoxy, propionyloxy or bivaloyloxy; cyano; phthalimide: C ffi-10 acylamide, such as acetamide or penzamide; C.
, alkoxycarbonylamino, such as metquinylamino or ethoxycarbonylamino, or C
? -+o Alalco-calponylamino, such as pencyloxycarponylamino; cyclic amino group (e.g., pyrrolidino, morpholino, etc.); Examples include good phenyl (the group of these substituents is hereinafter referred to as the P group). Among these, especially i + hydroxyl group. c, s alkoxy, c,
-e alkyl, halogen, nitro, amino 1 mono- or di(C,-.alkyl)amine + CI-6 alkylthio, amidino, ami/CI-6 alkyl, cyano,
C11 alkoxycarbonyl+CI-6 alkoxycarbonyloxy, phenyl, phenylamidino, and alkoxyformimidoyl are preferred. Furthermore, methyl, methoxy, and chlorine. Particularly preferred is fluorine.

In addition, the carboxyl acyl group represented by R1 generally has the formula R3CO- (wherein R3 is a saturated or unsaturated aliphatic group which may have a substituent or a saturated or unsaturated aliphatic group which may have a substituent). This indicates a good aromatic ring group.).

The aromatic ring group represented by R3 includes an aromatic carbocyclic group and an aromatic heterocyclic group. An example of the former is phenyl. Examples include naphthyl.

The aromatic heterocyclic group is preferably a 5- to 6-membered aromatic abdominal ring containing 1 to 4, preferably 1 to 2, heteroatoms such as nitrogen, oxygen, and sulfur. Specific examples of aromatic heterocycles include:
Examples include pyridyl, furyl, chenyl, birazinyl, virolyl, imidazolyl, isohandsazolyl, and the like.

Furthermore, such an aromatic ring group may include the same or another aromatic ring (
A group in which aromatic heterocycles and aromatic carbocycles as described above are condensed is also preferable. Examples of these condensed rings include indolyl, penzimidazolyl, oxnoryl, imidazopyridyl, and thiazolopyrinyl.

As the substituent that the aromatic carbocyclic group may have, for example, groups remaining from the above-mentioned P group are preferable.

Examples of substituents that the aromatic heterocyclic group may have include amino (C, -18 acyl, halogen-substituted C, -
, acyl, phenyl, C, ~3 alkyl as a substituent? You may also have one. ), halogen, nitro, sulfo, cyano, hydroquine, carboxy, oxo, C , . a, alkyl (phenyl, halogen, amino, hydroxy/,
It may have carboxy + C + -3 alkoxy + C I-3 alkylsulfonyl, C1-3 dialkylami7, etc. as a substituent. ), C3. Cycloalkyl+CI-3alkoxy+Ct-1. Acyl, phenyl (may have halogen, nitro, alkyl, alkoxy, ami/sulfo, hydroquine, cyano as a substituent), oxo, C1■0 alkylthio (phenyl, halogen, amino, hydrocyan, carboxy,
It may have C,-3alfoxy+CI-3alkylsulfonyl, di-C1-37-alkylamino, etc. as a substituent. ) (the above group of substituents is hereinafter referred to as group H). Among these HWs, especially CI-10 alkyl, amino, mono or
C1-3 alkyl)amino, halogen, amino/C,
-3 alkyl and the like are preferred.

The aliphatic group represented by R3 may be a saturated group or an unsaturated group, and includes, for example, an alkyl group, an alkenyl group, and an alkynyl group. In addition to the lower alkyl groups mentioned above as the alkyl group represented by Rl, the alkyl group also includes higher alkyl groups having 7 or more carbon atoms such as hebutyl, octyl, nonyl, decyl, undecyl, dodecyl, heptadecyl, and octadecyl. It will be done. The alkyl group represented by R3 is preferably an alkyl group having 1 to 18 carbon atoms.

The alkenyl group and alkynyl group represented by R3 are preferably the groups described above with respect to Rl. The alkenyl group and alkynyl group are particularly preferably those having 1 to 4 carbon atoms.

As the substituent that the saturated or unsaturated aliphatic group represented by R3 may have, it may be substituted with a substituent from the group A or the group P as described above. A phenyl group, a phenyl amino group or pensylamino group which may have a substituent from the above group P on the ring, a heterocyclic group which may be substituted with a substituent selected from the above group H, etc. Can be mentioned. Here, the heterocyclic group includes, in addition to the aromatic heterocyclic group mentioned above regarding the aromatic ring group represented by R3, a partially or fully saturated heterocyclic group (e.g., morpholino, piperidinyl, piperidino,
piperazinyl, pyrrolidinyl, etc.).

Examples of the aliphatic group represented by R2 include saturated or unsaturated aliphatic groups as described above for R. As the alkenyl group of the unsaturated aliphatic group roughly represented by R2, in addition to the lower alkenyl groups mentioned as examples of R1, alkenyl groups having 7 to 10 carbon atoms are also preferable. Examples of substituents that the aliphatic group represented by R2 may have include the same substituents as the aliphatic group represented by R3 above, and further substituted with an oxo group, etc. You can.

Further, examples of the aromatic ring group represented by R2 include aromatic carbocyclic groups, aromatic heterocyclic groups, and condensed ring groups thereof as described above for R3. The substituent that may be present on an aromatic carbocyclic group is a group selected from the above group P, and the substituent that may be present on an aromatic heterocyclic group is a group selected from the above group H. can be given respectively.

The number of substituents in the optionally substituted group represented by R', R'' is 1 to 5, preferably 1 to 3.

In formula [1], Rl is a hydrogen atom or a carboxylic acid acyl group (the anru group is preferably an acetyl group, a flobionyl group, etc., and the methyl group or ethyl group in these groups is a substituent as described above) ).
Compounds are preferred.

Particularly preferred are compounds in which R' is a hydrogen atom. R2 is preferably a compound which is a phenyl group which may have a substituent or an alkenyl group which may be substituted with an aromatic ring which may have a substituent.

In particular, an aliphatic group optionally having a substituent of R2 in the formula R'X (wherein R4 is an aromatic ring group optionally having a substituent, A compound represented by an unsaturated aliphatic group capable of forming a conjugate bond with the thiazole ring is preferred. Here, as for the ``aromatic ring'' and the ``substituent'' of the aromatic ring group ゛゜ that may have a substituent represented by R4, the same applies as described above for R3.For X, For example, CH=CH-, -CH=CH-CH=CH, etc. Furthermore, R' is a hydrogen atom, and R2 is a phenyl group which may have a substituent, or phenyl, chenyl, furyl, pyridyl. , pyrazinyl or imidazolyl group, which is an alkenyl group conjugated with a thiazole ring having 2 to 4 carbon atoms is a preferred embodiment from the viewpoint of its function. Particularly preferred examples of optionally substituted alkenyl groups include vinyl substituted with optionally substituted phenyl and butaneyl.

The above-mentioned compounds particularly excellent in terms of hypotensive effect [Doco-related, R S, R @. R? Examples of the lower alkyl group represented by include alkyl groups having 1 to 3 carbon atoms such as methyl group, ethyl group, probyl group, and isobrobyl group.

Aromatic ring groups represented by R 5 , R 6 and R' include phenyl group, pyridyl group, and chenyl group. Preferred are virolyl group, pyrazinyl group, and the like. A phenyl group is particularly preferred.

Examples of the substituents possessed by such an aromatic ring group include the substituents found in the above-mentioned P group. Examples of substituents for such aromatic ring groups include amide 7 groups and mono-lower alkyl amine 7 groups.
and di-lower alkylamino groups are preferred. Here, as a lower alkyl group as a substituent for an amino group, a carbon number 1 as mentioned above as an example of a substituent of the P group with respect to Rl is used.
-6 alkyl groups are mentioned. In particular, a diethylamino group is preferred as the substituent for the aromatic ring group.

When R5 and R7 form a ring, the ring may be a carbocyclic ring or a heterocyclic ring containing a heteroatom such as N, S, O, etc. as a ring atom.

Such rings include cyclopentane, cyclobentene, cyclohexane/chlorohexene, furan, thiophene, pyrrole. Examples include benzene, vinyl chloride, and the like.

In compound [V'], examples of the aromatic ring group of "the aromatic ring group substituted with an amino group or a substituted amino group" represented by Rll/ include the aromatic ring groups described above for R6, especially phenyl groups. is preferred.

The substituted amine 7 group in R8' is preferably a mono- or lower alkyl amine 7 group as described above as a substituent for the aromatic ring group represented by R6.

In addition, the compound represented by the general formula [1] has R', R
Although stereoisomers may occur depending on the type of substituent, not only these isomers alone but also mixtures thereof are included in the present invention.

The salt of the compound represented by the general formula [1] is preferably a pharmaceutically acceptable salt, and examples of pharmaceutically acceptable salts include hydrogen halides (e.g., hydrogen chloride, hydrogen bromide), Inorganic acids such as phosphoric acid and sulfuric acid and organic carbonic acids (e.g.
Examples include organic acids such as oxalic acid, phthalic acid, fumaric acid, maleic acid) and sulfonic acid (L methanesulfonic acid, benzenesulfonic acid). Also, compound [+] is R' or R2
When the above substituent has an acidic group such as a carboxyl group, inorganic base salts with alkali metals (e.g., sodium, potassium) or alkaline earth metals (e.g., magnesium) and organic bases (e.g., dicyclohexylamine, triethylamine) , amines such as 2,6-lutidine).

Hereinafter, the compound represented by general formula [1] and its salt will be collectively referred to as compound [r].

Compound [1] of the present invention can be produced, for example, by the method shown in Scheme -■.

Scheme-■ or a salt thereof [1] or a salt thereof [II] Rl or a salt thereof [+] [In scheme-I, Rl and R2 have the same meanings as above, R'C
oX represents a reactive derivative of carboxylic acid. ] That is,
Compound [1] or a salt thereof (salts include the salts listed above as the salt of compound [I]) with the formula R "C O
Compound [1] can be obtained by acylating with a reactive derivative of carboxylic acid represented by X to obtain compound [Ir], and then treating [I['1] with a sulfurizing agent. More specifically, the reactive derivatives represented by R'COX include acid chlorides, acid bromides, imidazolides, acid anhydrides, acid azides, N-phthalimide esters, N-oxysuccinimide esters, and the like. Moreover, instead of using an active ester, the carboxylic acid represented by R'COOH can be replaced with N,N'-dicyclohexylcarpodiimide (
Hereinafter, it may be abbreviated as DCC. ) may be directly reacted with the compound [I[1] in the presence of a canobling reagent such as ).

About 1 to 3 moles of the reactive derivative represented by R'C O
Use 2 moles. When reacting with a carboxylic acid represented by R'COOH, usually about 1 to 3 moles of carboxylic acid, preferably about 1 to 1.2 moles, is added to 1 mole of compound [11I], and about 1 to 1.2 moles is added to the same compound [II1]. React in the presence of ~1.2 moles of Canobling reagent.

The reaction usually proceeds smoothly under water cooling or in room a (room temperature in the following description of the manufacturing method specifically means 5 to 35°C). The solvent used at this time may be any solvent as long as it is inert to the reaction, and is not particularly limited, but chloroform, methylene chloride, tetrahydrofuran, dioxane, dimethylformamide, etc. are often used. When using an acid chloride or an acid bromide as an acylating agent, it is desirable to add an amine such as triethylamine or pyridine to the reaction system. The reaction time is usually about 30 minutes to 12 hours, although it depends on the reagent, solvent, and temperature used.

The reaction for converting compound [I1] into compound [I] is carried out in the presence of a sulfurizing agent such as phosphorus pentasulfide or Lawesson's reagent. The amount of sulfurizing agent used at this time is generally compound [I1]1
It is preferably about 1 to 3 moles per mole, usually about the same mole as that of compound [I[]. Pyridine is preferable as the reaction solvent, but there is no particular restriction. The reaction is carried out at a temperature of about 50° to 120°C, preferably about 80° to 120°C. Although the time required for the reaction varies depending on the reaction temperature, it usually takes about 3 to 12 hours. For example, if the reaction is carried out at about 100° C. to 120° C., the reaction will be completed within about 5 hours.

In the scheme -■, the substituent represented by R1 is R1 at any stage.
Alternatively, it is usually advantageous to convert the R1 portion after obtaining the compound [1]. In such a conversion reaction of Rl, a compound in which R1 is a hydrogen atom is subjected to a reaction such as alkylation, sulfonylation, or acylation by a conventional method, and R' is converted to an optionally substituted alkyl group, sulfonic acid, etc. Examples include reactions to obtain the target compound which is an acyl group or a carboxylic acid amyl group.

These reactions can be carried out according to methods known per se, but can also be carried out, for example, by the following methods.

A compound in which Rl of compound [I] is a hydrogen atom [hereinafter sometimes referred to as compound [1] (R'=H). ], R1
is an acyl group, compound [1] (R
'=H) may be acylated. In order to obtain a compound in which Rl is a carboxylic acyl group, a reactive derivative of the carboxylic acyl group may be reacted with compound [I] (R'=H). Regarding the type of reactive derivative of acyl carboxylate, reaction conditions, etc., those described above for the reaction to obtain compound [n] from compound [I11r] are generally applied as they are. Under these conditions, the reaction proceeds smoothly. Compound [1] (
In order to lead to a compound in which Rl is ar/al sulfonate (R'=H), it is convenient to react the compound [I] (R'=H) with a sulfonyl halide. The reaction is usually carried out in the presence of an amine such as triethylamine or pyridine. The solvent used at this time may be any solvent as long as it is inert to the reaction, but acetone, dioxane, dimethylformamide, tetrahydrofuran, chloroform, methylene chloride and the like are preferably used. Pyridine may be used as a solvent in some cases. The reaction is O0
C~Proceeds smoothly at room temperature and completes in 30 minutes to 5 hours. The amount of amine used at this time is about 1 to 3 moles per 1 mole of compound [1], and the amount of the acylating agent is about 1 to 2 moles.

To obtain a compound in which R1 is an alkyl group from a compound in which R1 is a hydrogen atom, compound [I] (R'=
H) may be subjected to an alkylation reaction. The alkylating agents used at this time include alkyl halides (halogens include chlorine, bromine, and iodine), alkyl esters of sulfonic acid (alkyl esters of Lp-toluenesulfonic acid,
alkyl esters of methanesulfonic acid, etc.). The amount of alkylating agent used is about 1 to 2 mol per 1 mol of compound [I]. The reaction is usually carried out in the presence of an inorganic base such as potassium carbonate or sodium carbonate, or an organic base such as triethylamine or pyridine. The base is preferably used in an equimolar amount with the alkylating agent. The solvent used is not particularly limited, but for example, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, etc. are preferably used. The reaction is usually carried out under heating, suitably in the range of about 30° to 100°C.

A compound [1] in which R' is an alkyl group can also be obtained by reducing a compound [N] in which Rl is a carboxylic acid acyl group.

Although the reduction can be carried out according to conventional methods, reduction using a reducing agent such as lithium aluminum hydride or diborane is suitable. At this time, ether, tetrahydrofuran, or dioxane is used as the solvent, and the reaction usually proceeds under reflux.

Compound [1] can also be produced by other known methods or methods similar thereto.

In addition, compound CIII, which is a raw material compound for the production method of the present invention,
], compounds in which R1 is a hydrogen atom are known compounds, and compounds in which R1 is other than a hydrogen atom are described, for example, in J. P
．． The method of Snyder et al. [J, P. Snyder
etal. , Journal of Medicinal Chemistry (J. Med. Chem.), 29
, 2 5 1, (1 9 8 6)] according to the scheme -H
It can be synthesized using the following method.

Diagram ■ [In the formula, R1 has the same meaning as above, and X represents a norogen atom as B
OC represents a tert-butoxycarbonyl group] In some cases, the compound [IE] can also be produced from a compound where R1 is a hydrogen atom, according to the reaction for converting the R1 moiety of the compound [+] described above.

When R2 is an alkenyl group, the trans isomer may be appropriately isomerized to the trans isomer, and the trans isomer may be isomerized to the /s isomer, as appropriate, by a normal isomerization reaction such as photoisomerization.

Compound [1] obtained by the above method can be isolated and purified by conventional separation means such as recrystallization, distillation, and chromatography.

If the compound [+] obtained in this way is obtained in a free form, it can be converted into a salt by neutralization etc. by a method known per se.On the other hand, if it is obtained in a salt form, it can be converted into a free form by a conventional method. can be changed to

The compound [I] of the present invention is a polyunsaturated fatty acid (linoleic acid, γ
-Linolenic acid. α-linolenic acid, arachidonic acid, dihomo-γ-linolenic acid, eicosapentaenoic acid) metabolic improvement, especially the effect of suppressing lipid peroxide production reaction (antioxidant effect), 5-riboxygenase metabolite E example, leukotrienes, 5-hydroberoxyeicosatetraenoic acid (
HPETE), 5-hydroquineicosatetraenoic acid (
HETE), riboxins, leukotoxins, etc.], thromboxane A, synthetic enzyme inhibitory effect, prostaglandin I, synthetic enzyme retention promoting effect, LT
D. In addition to circulatory system-improving effects such as receptor antagonism and scavenging of reactive oxygen species, and antiallergic effects, it also has potassium channel activating effects.

Compound [1] has low toxicity and side effects.

Therefore, the compound [+] of the present invention is useful as a therapeutic agent for cardiovascular diseases such as hypertension and angina pectoris in mammalian animals (mice, rats, rabbits, dogs, monkeys, humans, etc.).

Compound [1] can be administered orally as it is or as a pharmaceutical composition (e.g., tablet, capsule, liquid, injection, suppository) mixed with known pharmaceutically acceptable carriers, excipients, etc. It can be safely administered parenterally. The dosage varies depending on the subject, administration route, symptoms, etc., but for example, when orally administered as a single dose to an adult patient, it is preferably about 0.1 to 1 O O mg/person. is about 0.3 to 50 mg/adult, more preferably about 0.5 to 20 mg/adult, and in the case of intravenous administration, about 0.1 to 20 mg/adult, preferably about 0.
3~] It is convenient to administer about 0mg/adult about 2 to 3 times a day.

Effects of the Invention The compound of the present invention has potassium channel activating effects, etc., as shown in the following test examples, and is useful as a medicine for the treatment and prevention of circulatory 2g-related diseases, hypertension, etc.

Test Examples, Examples, and Reference Examples are described below, but the present invention is not limited thereto.

Tanichiri test example 1 Effect on Rasotho aorta specimen 1) Inhibition rate of contraction induced by tetraethylammonium chloride (TEA) and barium chloride (Ba) in a liquid bath of 20 d (Krebs-Henseleit)
Liquid 37°C, 95% 0. A La Noto aortic ring specimen was suspended in a -5% CO1 airflow). TEA and Ba
were added to a concentration of 45mM and 0.3mM, respectively, to induce contraction. After the contraction reached a steady state, the test compound was added to a concentration of 10-5M and its relaxing effect was examined. The contraction tension due to TEA+Ba was set as 100, and the magnitude of the relaxing effect was expressed in %, which was defined as the TEA+Ba contraction inhibition rate.

2) 80mM potassium chloride (K C f!) Effect on contraction KCQ was used as a contraction inducing agent instead of TEA + Ba.
The relaxation effect was examined and the contraction inhibition rate was determined in the same manner as in 1) except that the concentration was 0 mM.

As shown above, the compound of the present application suppressed TEA+Ba contraction by 8-100%, but had no effect on the contraction of 80mMKC (2). It is thought that it exhibits a relaxing effect by opening potassium channels.

Test Example 2 Antihypertensive effect of male Wis under anesthesia
Experiments were carried out using tara under anesthesia with bentobarbital. Blood pressure was measured via a cannula inserted into the right carotid artery. The test drug was administered via a cannula placed in the right femoral vein.

Results: When 1 mg/kg of drug was administered, it was administered 1 to 2 minutes later.The above results show that the compound of the present application has a hypotensive effect.

EXAMPLES Hereinafter, the present invention will be explained in more detail by reference examples and examples, but the present invention is not limited to these examples.

The elution in column chromatography in the following examples was performed using TLC (Thin Layer Chromatography).
The analysis was carried out under observation using thin layer chromatography (atography). For TLC observation, Kiesselkel 60F manufactured by Merck was used as a TLC plate.
250 (70 to 230 mm) was used as the developing solvent, the solvent used as the elution solvent in column chromatography was used as the developing solvent, and a UV detector was used as the detection range. The silica gel for the column is Kieselgel 6, also manufactured by Merck.
0 (70-230 menosh) was used. The NMR spectra show proton NMR and are VARIANE M390 using tetramethylsilane as internal reference.
(90 MHz type Subect Meter), and the δ value was expressed in ppm.

The abbreviations used in the examples have the following meanings.

s, nongrenote, br: broad, d:
doublet, t: triplet, q. quartet, m
Multi-bullet, dd: double bullet, double bullet,
j: Canobling constant, Hz: Hertz, CDCQ. : Deuterated chloroform, ds-DMSO: Deuterated dimethyl sulfoxide, %/wt% Also, room temperature means about 15 to 25°C.

The melting point and temperature are given in Mr. Nanano.

Reference Example 1 3-(4-chloronnamoyl)amino-ε-caprolactam p-chlorocinnamic acid 13. 13.9 g of N,N'-carbonyldiimidazole was added to 500 d of THF solution of 0.0 g, and the mixture was stirred at room temperature for 20 minutes. Next, 3-amino-epsilon lactam 9. After stirring for 5 hours, the precipitated crystals were collected by filtration, washed, and dried under reduced pressure to obtain the title compound (llg). This compound was used in the next reaction without purification.

Melting point 256-257° IR(KBr)am': 319g, 16g6
．． 1644, 1614, 1563, L{48,
814 NMR (CDCR.) δ: 1.30 −
2.20 (6H, m), 3.203.42 (2H,
m), 4.55-4.78 (IH.m), 6.43
(LH, d, J1BHz), 7.10 (2H, ml
7J9 (2H, m), 7.56 (18, d, J=l6
}1z) The following compounds were obtained in the same manner.

Reference example 2 3-(4-methoxycinnamoyl)amino-ε capulactam melting point 238-239° I R (K Br) cn+-': 1672,
1650, 1604, 1532, 1511,
1257. 11?2. N M R (do D
M SO ) δ: 1. 1g - 1. 85
(6H, m), 3.07-3. 25 (28,
m), 3. 76 (3H, s), 4. 52
(LH, dd, J7Hz, 10Hz), 6.7
7 (IH, d, J=16Hz), 6.95 (2H,
d, J-8Hz), 7.34 (IH, d, J=
16Hz), 7.51 (2H, d, J=8Hz),
7.84 (IH, t, J=5Hz), 7.97
(18, d, J=7Hz). Reference example 3 3-nnnamoylamino-ε monolactam melting point 19
4-196°IR(KBr)cm-': 3294, 2924
, 1656, 1619, 1536. 14g0,
1433. 1226NMR (CDCQ.3) δ:
1. 28-2. 23 (6H, m), 3.
093. 40 (2H, m). 4. 56-
4. 79(1}1, m), 6. 49 (IH,
d, J= 15Hz), 6. 90-7. 6
0 (5H, m), 7. 61(In, d, J=
15Hz) Reference Example 4 1(2-phenylbutyryl)amino-ε-cabrolactam Melting point 152-153° I R(KBr) cm-'+ 3280. 293
4, 1641, 1531, 1479. 14
36. NMR (CDCff3): 0.8g (38,t,J
=7Hz), 1.33 2.32 (8H, n+)
, 3.13-3.37 (2H, +n). 4.0
0(1}1,t,J=7Hz), 4.36-4.6
1 (IH, m), 7.30 (5H.s). Reference example 5: 3-(4-methoxybenzoyl)amino-ε-1 turnip lactam Melting point 214-215° I R(K Br) cm-': 2926, 1641
, 1548, 1505, 1246. 1187. NMR (d.-DMSO) δ: l. 17-2.
02 (6H, m), 3.11-3.30 (2H,
m), 3.82 (3H, s), 4.56-4.64
(IHm), 7. 00(2H, d, J= 9H
z), 7. 83 (2H, d, J=9Hz),
8,09 (li{, d, J = 6Hz) Reference Example 6 3-(4-methylnnnamoyl)amino-ε-1-cubic lactam melting point 229-230' I R(K Br) am-': 3196. 2932
, 1685, 1610, 1347 807 NMR (CDCf23) δ: 1.22-2.28 (6
H, m), 2, 37 (3H, s). 3. 2
3-3. 50 (2H.m). 4. 59
- 4.81 (IL m), 6.46 (IH.d, J=
16Hz). 7.20 (2H, d, J=9Hz).
7.43 (2H, d, J = 9Hz),
7.63 (IH, d, J= 16Hz). Reference Example 7 1(4-Ethoxycinnamoyl)amino-ε monolactam Melting point 236-237° I R(K Br) cm"-': 16g6, 164
4, 1605, 1562, 1513. 1{04,
1233. 1173. NMR(d.-DMSO)δ
: 1,32(3}1,t,J=7Hz), 1.20
-2.00 (6H, m), 3.09-3. ．． 33(
2H, m), 4.06 (2H, q, J=7Hz),
4.44-4.63 (IH, m), 6.72 (IH
, d. J=16}1z). 6. 93 (2H, d,
J=9Hz), 7. 32 (IH, d, J=
16Hz). 7.50 (2H, d, J=9Hz).
Reference Example 8 1(4-isobrobylcinnamoyl)amino-ε monolactam Melting point 199-200° I R(K Br) cm-': 3320, 16
70, 1651. 16151528, 14
30. NMR (d.-DMSO) δ: 1.18 (6H, d.
J=6Hz), I. 33-2.00 (6H, m),
2.81-2.98 (IH, m), 3.04-
325 (2H, m), 4.43-4.63 (1B,
m), 6.83 (IH, d, J-16Hz),
7, 24 (2H, d, J = 7Hz), 7.38 (I
H, d, J = 16Hz), 7.50 (2H, d, J
=7Hz). Reference Example 9 3-[5-(4-methoxyphenyl)pentadienoyl]amino-ε monolactam Melting point 204-206° I R(KBr)cttr-': 1645, 159
8, 1510, 1480, 1435, 1255.
1176, 1029. NMR (d,-DMSO)
δ: 1.15-1.93 (68, m), 3.00
-3. 20 (2H, m), 3. 77 (3H,
s), 4. 38-4. 61 (1B, m),
6. 26 (IH, d, J= 14Hz), 6
．． 83-7. 05 (3H, m), 6. 91
(2H, d, J= 8Hz), 7. 50 (2H
, d, J = 8 Hz) Reference Example 10 3-(4-impaboxycinnamoyl)amino-ε-1-cubic lactam melting point 2'2 5 - 2 2 6° I R (K Br) cm': 1671, 1
651, 1606, 1535, 1510,
1254. NMR (CDCl23) δ: l. 16-2. 3
0 (6H, m), 1. 32 (6H, d, J
= 6Hz), 3. 12-3. 40 (2H
, m), 4. 56 (IH, septet, J=
6Hz), 6.33 (1}1, d, J=16Hz)
, 6.83 (211d, J=9Hz), 7.4
1 (2H, d, J=9Hz), 7.55 (18, d
, J=16Hz). Reference Example 11 3-(3.5-di-t-butyl-4-hydroxycinnamoyl)amino-ε-cabrolactam Melting point 112-11
3° IR(KBr)clTl-': 2956, 16
57, 1615. 14791435. 120g
．． NMR (d..-DMSO) δ: 1.10-2.00
(6H, m), 1.39 (18H.s), 3.0
4-3.32 (2H.m), 4.4:{-4.65(
ltl, m). 6.76 (IH, d, J=16Hz)
, 7.29 (LH, d, J=16Hz), 7. 31
(2H, s) Reference Example 12 3-(2-methoxy/annamoyl)amino-ε Kabuchi lactam Melting point 213-214° I R(K Br) cm-': 3216, 1685
, 1643, 1613, 1557. 144g,
1245. NMR (d.-DMSO) δ: 1.18-1.96 (
6H. m), 3.03-3. 27(2}1, 0
+), 3. 83(3}1.s), 4. 43
-4. 65(1}1,m), 6.76-7.56
(6H, m). Reference Example 13 1(3.4-methylenedioxycinnamoyl)amino-ε-1-cubic lactam Melting point 275-276° I R(K Br) am-': 1669, 1652
, 1616, 1532, 1500, 1488,
1250. NMR (d.-DMSO) δ: 1.17
-1.95 (6H, m), 3.05-3.32 (2H
, m), 4.40 - 4. 60 (IH, m),
6. 03 (2H, s), 6.73 (1B, d, J
=16Hz), 6.80-7.17(3}1,+n)
7. 30 (IH, d, J= 16Hz). Reference Example 14 3-(α-Phenylcinnamoyl)amino-ε-caprolactam Melting point 159-160° I R(K Br) cm-': 3354, 32
54, 1656. 1617, 1501, 1
445, 709. NMR (d.-DMSO) δ:
1.22-1.98 (6H, m), 3.00-
3. 19(2}!, m), 4. 40 (IH,
dd, J=4Hz, 7Hz), 6.95
-7. 56 (IIH, m). Reference Example 15 3-(2,3.4-}rimethoxycinnamoyl)amino-ε-cabrolactam Melting point 208-209° I R (KBr>cm-': 1673. 1646,
1614, 1495, 1464. 1297. 1
097. NMR (d.-DMSO) δ:l, 18-1. 9
7 (6H, m), 3. (18-3.22(2H, m
), 3.75(3H,s), '3.80(3H,s
), 3.82 (31, s). 4.43-4.63(
IH, n), 6.79 (LH, d, J16Hz).
6.89 (IH, d.J=9Hz). 7.32 (lH
．． d, J=9Hz). 7.53 (1B, d.J=16
Hz). Reference example 16 3-(3.4-dimethocycinnamoyl)amino-ε-caprolactam melting point 185-186° IR(KBr)cn+-': 3302, 1
650, 1611, 1514, 1468,
1260, 1137. NMR (d.-DMSO)
δ: 1. 18-1. 96 (6H, m),
3.08-3.29(21{,n+), 3.79(
3H,s), 3.81(3H,s), 449
-5. 08 (LH, m), 6. 86 (18
, d, J= 16Hz), 6. 98(LH,
d, J=8Hz), 7. 13(IH, d
d, J= 2Hz, 8Hz), 7, 23(it
{,d,J=2Hz), 7.34(IH,d,J=
16Hz). Reference Example 17 3-(3,4-dimethoxybenzoyl)amino ε-cabrolactam 3,4-dimethoxybenzoic acid 10. 9.79 g of N,N'-canolebonyldiimidazole was added to IFFL300JI12 in which Og was dissolved in tetrahydrofuran, and the mixture was heated for 30 minutes at room temperature.
Stir for a minute. Next, 3-amino-ε-cabrolactam 7
．． After stirring for 5 hours, the precipitated crystals were collected by filtration, washed, and dried under reduced pressure to obtain the title compound (8.5 g). This compound was used in the next reaction without purification.

Melting point 190-191° l R (K B r) cm-': 1657,
1617, 1574, 1510, 1476.12
63 NMR (ds-DMSO) δ: l. 16-
2. 00 (6H, m), 3. 03-3. 25(
21{, m), 3. lli+(6H, s),
4. 57-4. 65 (IH, m), 7. 02(
11{, d, J = 8Hz), 7. 43-7
．． 50(2H, m), 7, 83-7. 89 (I
H, m), 8. 15(If{, d, J= 7
Hz). The following compounds were obtained in the same manner.

Reference example 18 3-(3-methoxycinnamoyl)amy7-εcafrolactam Melting point +73-174° l R (K B r) am': 3312, 1
671, 1653, 1621. 15781540
, 1434. 1289 NMR (dll-DMS○) δ: I. +5-2.
00(6H, m)3. 12-3. 28 (2B.
m). 3. 79 (38, s), 4. 54(
Ift, dd, J= 3Hz, 7Hz), 6.
92-7. 4 1 (6H, m), 7. 88 (I
H, t, J = 4Hz), 8. 05(IH,
d, J = 71tz). Reference 4 Example 19 3-(3.5-dimethoxy/nnnnamoyl)amino ε-cafrolactam Melting point 174-175° I R (K B r) cm-': 1654,
1619, 1535, 1426. 1208116
0, NMR (d, DMS○) δ: 1. 20-1. 9
7 (6H, ml3.09-3.32(2H, m
), 3. 77 (6H, s), 4. 53 (IH
, dd, J= 4Hz, 7Hz), 6.50(
IH, t, J = 2Hz), 6. 77 (2H
, d, J = 2Hz), 6. 98 (IH,
d, J −= 16Hz), 7. 32 (IH,
d, J = 16Hz), 7. 88 (IH, t
, J = 6Hz), 8. 01(IH, d,
J = 787. ). Reference Example 20 3-(2.3-dimethocycinnamoyl)amine ε~cabrolactam melting point 187-188° I R (K B r) cm"-': 3208.
1686, 1613, 1577. 14g0,12
70. NMR (da-DMS○) δ: 1. 18-1.
89(6H, ml3.09-3.28(2■,
m), 3. 75 (3H, s), 3. 82(3
H, s), 4. 54 (IH, dd, J-
3Hz, 7Hz), 6. 93 (IH, d, J
= 16Hz), 7, 037. 22(3}1,
m), 7. 64 (IH, d, J = ] 6
}1z), 7. 85 (III, t, J-6Hz
), 8. 13 (IH, d, J = 7 Hz) Reference example 21 3-(2.51-methoxynnnonamoyl)amino ε-1-cubic lactam Melting point 19Cl191° I R (K B r) cm': 1655, 1
600, 1524, 1494. 1431.122
3 NMR (d.-DMSO) δ: 1.20-1.93
(6H, m)+3. 00-3. 26 (28, m)
, 3. 75 (3H, s), 3. 80 (3H,
s), 4. 54 (IH, dd, J = 2H
z, 6Hz), 6. 92-7.01 (3H, m
), 7. 14 (IH, d. J = 31{z),
7. 64 (IH. d, J= 16Hz), 7
．． 88 (IH, t, J=7Hz), 8. 02
(18, d, J-8Hz). Consideration Example 22 3-(4-Methoxy3-methylcinnamoinole)amino-ε-1-cubic lactam Melting point 2+8-219° I R (K B r) am-'° 3280. 292
0. +660. 1640, 1600.1500
1248.1122 NMR (d.-DMSO) δ: 1.20-1.92
(6H, m), 2. I 6 (3H, s), 3.
06-3. 25 (2H, m), 3. 82 (3L
s), 4. 484. 57 (18. m). 6
．． 78 (IH, d. J = 16Hz), 6.
97 (ltl, d, J911z). 7. 31
(I}I, d, J = 16Hz), 7. 39
-7.42(2}1, m)7. 86(1}1, t
, J=5Hz), 7. 95 (IH, d, J
= 7Hz) Reference Example 23 3-[4-methoxy3-(2-methylthioethquine)
Nannamoyl] amino-ε monolactam melting point 19
2-193° I R (K B r) am-': 1673, 1
650, 1610, 1511. 1428.126
2 1143. NMR (d@-DMSO) δ: 1.19-1.97
(6H, m), 2. 18 (3B, s). 2. 8
7 (2H, t, J = 7Hz), 3. 024
．． 2g (21m), 3. 79 (38.s),
4. 17 (2H, t, J = 7Hz), 4.
52 (IH, dd, J= 3Hz, 5Hz),
6. 84 (IH. d, J = 16Hz). 6
, 98 (18, d, J-8Hz), 7. 13(
IH, dd, J = 3. 8Hz), 7. 2
4 (IH, d, J = 3Hz), 7. 32(
1B, d. J = 16Hz), 7. 85-7
．． 91 (2H, m) Reference Example 24 3-(3,4.5-1-rimethoxy/nnnnamoyl)amino-ε-1-cubic lactam Melting point 197-198° I R (K B r) cm-': 1667, 1
645, 1600. 157g, 1502.141
1 1122 NMR (d.-DMso) δ: 1. 18-1.
97 (6H, m), 3. 03-3. 24 (2H,
m), 3. 69 (3H, s), 3. 82(
6H, s), 4. 53 (18, dd, J =
3Hz, 7Hz), 6. 95 (2H, s),
6. 96 (IH, d, J16Hz), 7.
34 (IH, d, J-16Hz), 7. 89-
1. 93 (2H, m). Reference Example 25 3-(2.4-dimethquine cinnamoyl)amino ε-capsulactam Melting point 207-208° I R (K B r) am-': 3294. 1
678, 1644, 1599, 1519.121
2 1159. NMR (d.-DMS○) δ: 1. 21-1.
89 (6H, m), 3. 07-3. 20 (2H,
m), 3. 81 (3H, s), 3. 86(
3H, s), 4. 53 (IH. dd. J =
3Hz, 7Hz), 6. 56-6. 61(2
H, m), 6. 78 (IHd, J = 161
{z), 7. 49 (IH, d, J = 9Hz)
, 7. 58 (LH, d, J16Hz), 7.
84 (IH, t, J = 6Hz), 7. 9
5 (LH, d, J = 7Hz) Reference Example 26 3-(3-bromo-4-methoxycinnamoyl)amino-ε-monocaplactam Melting point 226-227° I R (K B r) cm"-': 1671,
1649, 1619. 1598. 1496,+
260. NMR (d.-DMSO) δ: 1.19-1.96
(6H, m), 3. 08-3. 25 (2H, m)
, 3. 89(31{, s), 4. 48-4.
57 (IH, m), 6. 89 (IH, d, J
= 16Hz), 7. 16(IH, d, J=
9Hz), 7. 33 (IH, d, J = 16
Hz), 7. 59 (LH, dd, J= 2Hz
, 9Hz), 7. 85 (IH, d, J= 2
Hz). Reference Example 27 1(3.5-di-tert-butyl-4-hydroquinbenzoyl)amino-ε-monolactam melting point 131-
132° I R (K B r) am-': 2954, 1
710, 1675, 1644. 14791427
, 1231. N M R (do D M SO ) δ: 1
．． 23-1.98 (6H.m), 1. 41 (18H,
s), 3. 09-3. 28 (2H, m),
4. 53-4. 62 (IH, m), 7. 59
(2H, s). Reference Example 28 3-(2.4-dimethoxybenzoyl)amino ε-caprolactam Melting point 196-197° I R (K B r) cm-': 3310, 1
669, 1494. 132g, 1261,121
0 1013. NMR (d.-DMSO) δ: 1.18-2.09
(6H, m), 3. 04-3. 24 (2H, m)
, 3. 83 (3H, s), 3. 95 (3H,
s), 4. 504. 58 (IH, m), 6
．． 63-6. 68' (2H.m), 7. 93
(IH, d, J= 9Hz). Reference example 29 3-(3.4-dimethylcinnamoyl)amino epsilon lactam melting point 226-227° I R (K B r) cm"-': 2934,
1685, 1643, 1613, 1562, 14
79. 1242. NMR (d.-DMSO) δ: 1. 16-1.
98 (6H, m), 2. 24 (6H, s), 3
．． 03-3. 21 (2H, m), 4. 49-
4. 58 (IH, m), 6. 88 ([1, d,
J=16Hz), 7. 17 (IH, d, J
= 8Hz), 7. 297. 37 (3H, m) Reference Example 30 3-(2-methoxy3-methylnnnamoyl)amino-ε-cabrolactam Melting point 186-187° I R (K B r) cm-' : 3270, 3
222. 16g4, 1638, 1621,156
9. 1467. NMR (d.-DMS○) δ: 1. 19-1.
98 (6H, m), 2. 26 (3H, s), 3
．． 06-3. 24 (2H, m), 3. 68(
38, s), 4. 51-4. 60 (IH, m
), 6. 94 (IH, d, J = 16Hz)
, 7. 09 (IH, t, J6Hz). 7.
24 (IH, d, J = 6Hz), 7. 47(
IH, d, J= 6}fz)7. 63 (IH,
d, J = 16Hz). 7. 87 (IH, t,
J = 5Hz), 8. 15 (IH, d, J
= 7 Hz), Reference Example 31 3-(3-methoxybenzoyl)amino-ε-cabrolactam Melting point 118-149° I R (K B r) cm-': 1680. 1
648. 15g7, 1542, 1487,130
0. NMR (d.-DMso) δ: 1.19-2.00
(6H, m), 3. 03-3. 27(2}1, m
). 3. 81 (38, s), 4. 57-4.
68 (IH, m)7. 07-7. 14 (IH,
m), 7. 35-7. 42 (3H, m). Reference Example 32 3-(α-Methylcinnamoyl)amino-ε-caprolactam Melting point 1 6 0 − 1 6 '1°I R (K
B r) cm-': 3384, 1672. 16
60, 1593. 1511l475 NMR (d.-DMSO) δ: 1. 18-
1. 96 (6H, m), 2. 03(3}1, s
), 3. 02-3. 27 (2H, m), 4.
46-4. 54 (IH, m)7. 29-7.
43 (6H, m). Reference Example 33 3-(4-trifluoromethylbenzoyl)amino-ε
-Cabrolactam melting point 283-284° IR (KBr) cm': 1687, 1
636, 1324, 1295, 1174.111
6 NMR (de-DMSO) δ: 1. 14-2.
00 (6H, m), 3. 04-3. 24 (2H,
m>. 4. 60-4. 71 (IH, m),
7. 86 (28, d, J= 811z), 8.
07 (2H, d.J=8Hz). Reference Example 34 3-(3.4-methylenedioxybenzoyl)amino-ε-1-cubic lactam Melting point 196-197° J R (K B r) Cm''-': 1660.
1635, 1602, 1475, 1253.10
33 NMR (d.-DMSO) δ: 1. 12-1.
99 (6H, n), 3. 08-3, 27 (2H,
II1). 4. 55-4. 62 (IH, II1
), 6. 11 (2H, s), 6. 99 (1B.
d, J = 8Hz), 7. 39 (IH, d
, J-2Hz), 7. 45 (LH, dd, J
= 2Hz. 8Hz). Reference Example 35 3-(p-}luoyl)amino-ε-caprolactam Melting point 202-203° I R (K B r) am-': 3262, 3
200, 1654, 1539, 1295, 128
2. NMR (d.-DMSO) δ: 1. 22-1.
98C6H, m'). 2. 36 (3H, s),
3. 03-3. 24 (28, m). 4. 56
-4, 64 (18, m) 7. 28 (2H, d,
J = 11! Hz), 7. 76 (2H, d,
J = 8[]z). Reference Example 36 3-(2,3.4-trimethoxybenzoyl)amino-ε-cabrolactam Melting point 240-24 1° I R (K B r) cm-': 3262, 1
678. 1656, 1634. 15191482
, 1093, NMR (d.-DMSO) δ: 1. 15-2.
08 (6H, m), 3. 08-3. 21 (2B,
m), 3. 78 (3H, s), 3. 85(
3H, s), 3. 90 (3H, s), 4.
52-4. 61 (IH, m), 6. 95 (18
, d, J = 9Hz). 7. 70 (IH, d,
J=9Hz). Reference Example 37 3-(3-trifluoromethylcinnamoyl)amino-[epsilon]-cubic lactam Melting point 201204° I R (K B r) cm-': 1673. 1
651, 1624, 1347, 1162.112
1 NMR (d.-DMSO) δ: 1. 17-1.
98 (6H, m), 3. 09-3. 36 (2H,
m), 4. 50-4. 59 (IH, m),
7. 15 (IH, d, J = 16Hz). 7.
50 (IH, d, J = 16Hz), 7.
61-7. 98(4}1,m) Reference Example 38 3-(N-tert-butquine carbonyl-β
-alanyl)amino-ε monolactam Melting point 11CIII° I R (K B r) cm-': 3346, 1
677, 1632, 1526, 1285.117
3 NMR(d,-DMSO) δ: 1.25-2.1g
(6B, m)+1. 42 (9B, s), 2. 4
1 (2H.t, J=6Hz), 3. 14-
3. 47(41{,m), 4. 41-4. 60
(1B, m). Reference Example 39 3-(4-methoxycarponylbenzoyl)amino-ε
Monocabrolactam melting point 226-227° I R (K B r) am-': 3306, 1
714, 1672, 1632. 1428.128
4. NMR (d.-DMSO) δ: l. 20-2.
02 (68, m), 3. 10-3. 22 (2H,
m), 3. 89(:{H, s), 4. 60
-4. 68 (1B, m), 7. 98 (2H, d
, J=9Hz), 8. 06 (2B, d, J
= 9Hz). Reference example 40 3-(4-ethoxycarbonylcinnamoyl)amino-ε monolactam Melting point 208-209° I R (K B r) cm"-': 1715,
1670, 1655, 1619, 1282, 12
72. NMR (d.-DMSO) δ: 1. 21-1.
98 (6H, m) 1. 33 (3H, t, J =
7Hz), 3. 07-3. 22 (2H.m)
．． 4. 33 (2B, ci, J=7Hz). 4
．． 50-4. 59 (1H, m), 7. 09(
IL d, J= 16Hz), 7. 46 (1B,
d, J = 16Hz), 7. 72 (2B,
d, J = 8}1z), 7. 98 (2H, d,
J = 8Hz). Reference example 4l 3 [4-(tert-butoxycarbonylaminomethyl)penzoyl]amino-ε-1-cubic lactam melting point
174-175° I R (K B r) am': 3364, 1
683, 1637, 1527. 1288.117
0 NMR (d8-DMSO) δ: 1.21-2.00
(6H, m), 1. 40 (9H, s), 3. 0
2-3. 28 (2H, m), 4. 17 (2H,
d, J = 8Hz), 4. 56-4. 65
(IH, m), 7. 32 (2H, d, J=
8Hz), 7. 80 (2H, d, J = 8H
z) Reference Example 42 22.5 g of 3-[1-(ethoxycarbonyloxy)cinnamoyl]amino-ε-monocarbolactam 3-hydroxy/-4-methoxycinnamic acid and 32.5 g of triethylamine. M was added to 400 d of tetrahydrofuran, and 22.2 d of ethyl chloroformate was added dropwise while stirring under water cooling. After the addition was completed, stir for another 15 minutes,
Subsequently, 200 ml of a solution of 14.9 g of 3-amino-[epsilon]-lactam in tetrahydrofuran was added dropwise, and after the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in chloroform. After washing this solution with water and drying, the solvent was distilled off under reduced pressure. The residue was washed with ethyl acetate and dried under reduced pressure to obtain the title compound (28 g). This compound was used in the next reaction without purification.

Melting point 209-210' I R (K B r)c+n-' : 1770,
1650, 1613, 1515, 1249, 12
17. NMR (CDCi23) δ: 1.23-1.95 (
6H, m), 1.37 (3}1, t, J = 7Hz
), 3. 20-3. 40 (2H, m), 3.
86 (3H, s), 4. 41 (2H, q,
J = 7Hz), 4. 55-4. 78 (IH
．． m), 6. 35 (IH, d, J=16Hz
), 6. 92 (IH, d, J = 9Hz),
7. 30-7. 40 (2H, m), 7. 51
(IH, d, J = 16Hz) The following compound was obtained in the same manner.

Reference Example 43 3-(4-Ethoxycarbonyloxybenzoyl)amino-ε monolactam Melting point 195-196° T R (K B r) cm-': 3312,
3266, 1766, 1683, 1634, 12
90,1252.1212 NMR (d.-DMSO) δ: 1. 40 (3H,
t, J=9Hz). 1. 53-2. 36(
6H, lTl). 3. 20-3. 41 (2H,
m), 4, 31 (2H, Q, J = 9Hzl 4
．． 58-4. 80 (IH, m), 7. 26(
2H, d, J = 8Hz), 7. 90 (2H,
d, J = 8Hz>. Reference Example 44 3-(4-cyanobenzoyl)amino-ε-cabrolactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 189-190° I R (K B r) cm-': 2224, 1
643, 1549, 1300, 937, 758
．． NMR (d.-DMSO) δ: 1. 17-2.
01 (6H, Rl), 3. 10-3. 26 (2
H. m), 4. 59-4. 60 (IH. m)
, 7, 96 (2H, d, J = 8Hz), 8.
03 (2H, d, J = 8Hz). Reference Example 45 3-(3-cyanobenzoyl)amino-epsilon-kabuchi lactam The title compound was obtained by the same method as in Reference Example 17.

Melting point 221-222° I R (K B r) cm-': 2932, 1
6g2, 1669, 1647, 1551,130
1. NMR (d.-D'MSO) δ: 1. 20-2.
00 (6H, m), 3. 09-3. 28 (2H
．． m), 4. 60-4. 71 (IH, m),
7. 70 (IH, t, J = 8Hz), 7.
84 (1B, t, J = 6Hz). 7. 9
9-1! I, 04 (IH, +n), 8. 15-1
20 (IH, m), 8. 31-8. 32 (IH
．． m), 8. 58 (LH, d, J=7Hz). Reference Example 46 3-(5-penzimidazolylcarbonyl)amino-ε
Monocabrolactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 297-299°. l R (K B r)c+n-': 3256,
1672, 1623, 1540. 1305128
9. NMR (d.-DMSO) δ: 1. 15-2. 0
2 (6L m), 3. 09-3. 26 (2H,
m), 4. 64 (IH. dd, J= 7Hz,
10Hz), 7. 64-8. 34 (6H, m
). Reference example 47 3-nicotinoylamino-ε-cabrolactam reference example l
The title compound was obtained in the same manner as in Example 7.

Melting point 220-221' I R (K B r) cm': 333 g, 1
677, 1646. 152g, 1418,133
4 NMR (do DMSO) δ: 1. 15-2.
01 (6H, m), 3. 023. 2B (2H,
m), 4. 60-4. 70 (IH, m),
7. 46-7. 55 (IH, m), 7. 83
(IH, t, J = 7Hz), 8. 20(
IH, dt, J = 2Hz, llHz), 8.
54 (IH, d, J = 7Hz), 8. 70
(IH, dd, J= 2Hz, 5Hz)9. 0
2 (IH, dd, J = IHz, 2Hz). Reference example 48 3-vicrinoylamino-ε-caprolactam reference example l
The title compound was obtained in the same manner as in Example 7.

Melting point 177-178°, I R (K B r) cm-': 16g5, 1
653, 1509, 1487. 14691424
．． NMR (d.-DMSO) δ: 1. 22-2. 1
1 (6H, m), 3. 033. 19(2}1,
m), 4. 52-4. 62 (1H, m>,
7. 60-7. 68 (IL m), 7. 98-
8. 16 (3H, m), 13. 66-8. 7
2 (IH, m), 9. 04(18, d, J =
6 Hz) Reference Example 49 3-[4-(4-Methylpiperazinyl)pensoyl]amino-epsilon-kabuchi lactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 232-234° I R (K B r) cm"": 3282, 1
679, 1544, 1513, 1451, 12
93 1244. N M R (da D M SO ) δ 1, 1
6-1. 98 (6H, m), 2. 22(3t{
, s), 2. 44 (4H, t, J = 5H
z), 3. 12-3. 21 (2H.m), 3.
25 (4H, t, J=5Hz), 4. 53
-4. 63 (IH, m), 6. 96 (28d,
J=9Hz), 7. 73 (2FI, d, J
= 9FIz) Reference Example 50 3-(1-methyl-IH-1.2.3-}riazole-
4-yl-carbonyl)amino-epsilon-capsulactam The title compound was obtained by the same method as in Reference Example 17.

Melting point 259-260°. I R (K B r) cm"-': 3388,
3108, 1677, 1640, 1571, 15
02. NMR (d.-DMSO) δ: 1, 13-2. 07C
6H, m). 3. 033, 28 (2H, m),
4. 09 (3H, s). 4. 55 (LH,
dd, J = 6Hz, 10Hz), 8. 05(
IH, t, J = 6Hz), 8. 26 (18
, d, J = 6Hz), 8.54 (18 s). Reference Example 5l 3-(indole-3-carbonyl)amino-ε Kabukuchi lactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 243-244° I R (K B r)cn+-': 3272,
1675, 1620. 154g, 1439,13
10. 1209. NMR (d, DMSO) δ: 1. 17-2. 01
(6}1, m), 3. 05-3. 26 (2H,
m), 4. 66 (18, dd, J = 7H
z, 10Hz), 7. 117. 20 (2B,
m), 7. 42-7, 47 (IH, m), 7.
71 (IH, d, J=7Hz), 7. 88-
7. 93 (IH, m), 8. 04-8. 09
(2H, m), 11. 63 (IH, br), Reference Example 52 3-(1-methylimidazol-5-ylcarbonyl)
The title compound was obtained in the same manner as in Amino-ε-Cabrolactam Reference Example 17.

Melting point 221-223° I R (K B r) cm-' + 3214. 1
670. 155g, 1532, 1477,124
0. NMR (d.-DMSO) δ: 1. 16-1. 9
9 (60, m), 3. 033. 24 (2H,
m). 3. 80 (3H, s), 4. 53-4
．． 63 (IH, m), 7. 02(IH, s),
7. 64 (IH. s>, 7. 83 (IH.
t, J= 6}1z), 8. 05(IH, d,
J=7Hz) Reference Example 53 3-(1-methylimidazol-4-ylcarbonyl)
The title compound was obtained in the same manner as in Amino-ε-Cab-Lactam Reference Example 17.

Melting point 223-234° T R (K B r) cm-': 3262, 1
663, 1641, 1567, 1484, 133
4. N M R (ds D M SO ) δ: 1.
16-2. 04 (6H, m). 3. 043.
2g (2H, m), 3. 69 (3H, s).
4. 42-4. 52 (IH, m), 7. 63
(IH, s), 7. 65 (IH, s), 8.
00 (IH, t, J=6Hz), 8. 09(I
H, d. J=6Hz). Reference Example 54 3-{β~(1-methylimidazol-4-yl)acryloyl}amino-ε-cabrolactam β-(1-methylimidazol-4-yl)acrylic acid (70 g,
0.3 7 mol) of dimethylformamide (500
d), triethylamine (75.1 g, 0.74 mol), l-hydroxy-7henzotriazole-hydrate (6
2.5 g, 0.4 1 mol) was added thereto, the mixture was cooled with water, and a dimethylformamide solution (50d) of dicyclohexylcarbodiimide (842 g, 0.41 mol) was added dropwise. After heating and stirring at room temperature for 1 hour and then at 70'C for 30 minutes, 3-amino epsilon-capsulactam (52.3 g,
0.41 mol) was added thereto, and the mixture was heated and stirred at 70'C for 14 hours. After cooling to room temperature, heavy backwater was added and extracted with a mixed solvent of chloroform and methanol. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography and recrystallized from ethanol to obtain 82.6 g (84.8%) of the title compound.

Melting point 244-246° (recrystallized from ethanol), I
R(KBr)am-': 3312. 32
30, 1678. 1655, 1625, 1512
, 1482, 1374. 1360. NMR (d.
-DMSO)6 1.10-2. 00 (6H, m)
．． 3. 13 (2H, m), 3. 65 (3H,
s), 4. 52 (IH, m), 6. 65(
IH, d, J15, 39Hz), 7. 25(I
H, d, J= 15. 39Hz), 7. 39
(IH, s), 7. 62 (18, s), 7.
77 (IH, br. t, J = 5. 90H
z), 7. 99 (IH, d, J= 7.32
Hz), elemental analysis value: Calculated value as C,3H,,N,02: C, 59.53; H, 6.92;
N, 21.36. Actual value: C, 59.30; H
, 7.13: N, 21.13. Reference Example 55 3-(β-(l-ethylimidazol-4-yl)acryloyl}amino-ε-cabrolactam By the same method as Reference Example 54, β-(1-ethylimidazol-4-yl)
The title compound was obtained from (yield: 94.8%) acrylic acid, triethylamine, 1-hydroxybenzotriazole-hydrate, dicyclohexylcarbodiimide, and 3-amino-ε-monolactam.

Melting point: 254-255° (recrystallized from ethanol),
I R (K B r) Cm': 3322, 1
681, 1657, 1631, 15061469
, 1370, 826. NMR (d.-DMSO) δ: 1. 15-1. 9
7 (6H, m), 1. 35 (3H, t, J=
7. 29Hz), 3. 13 (2H, m).
3. 99 (2H, q. J7. 29Hz), 4
．． 53 (IH, m), 6. 66 (IH, d,
J = 15. 4Hz). 725 (IH, d,
J=15. 4Hz), 7. 47 (II. s.
), 7. 69 (IH, s), 7.76 (lH,
t, J = 5.86Hz), 7.99(1}1, d,
J Ichigo. 24Hz>. Elemental analysis value: C,. H. N
．． Calculated value including O-: C, 60.85; H
, 7.29: N, 20.27. Actual value: C, 6
0.60; H, 7.49. N, 19.88 Reference Example 56 3-(2-quinolyl)carbonylamino-ε-cabrolactam Quinaldic acid, l, 1
The title compound was obtained from '-carbonylimidazole and 3-amino ε-monolactam (yield 95.1%).
.

Melting point: 248-250° (recrystallized from ethanol)
R(KBr)cm-': 3360, 321
6, 1655, 1564, 1515, 1498.
14g7, 1443, 1274. NMR (da-
DMSO) δ: 1. 15 ~2. 20 (6H,
m), 3. 23 (2H, m). 4. 67 (I
H, m), 7. 73 (LH, dt, J= 1
．． 43Hz. 7.55Hz), 7. 89 (In
, dt, J = 1. 43Hz, 7. 55H
z), 8. 05-8, 13 (4H, m). 8.
60 (IH, d, J = 8.44Hz).
9. 18 (IH, d, J = 6.23Hz). Elemental analysis value: Calculated value as C 18H INN 30 2: C, 67.83; H, 6. Q5;
N, 14.83. Actual value: C, 67.77. H
, 6.12; N. l4.74. Reference Example 57 3-(1.3-dimethylvirazol-4-ylcarbonyl)amino-ε-cabrolactam The title compound was obtained by pouring in the same manner as in Reference Example 17.

Melting point 236.0-237.0° I R (K B r) am': 3324.
327 (1. 1878, 1626, 1549.1
272 NMR (d.-DMSO) δ: 1. 15-1.
98 (6H, m), 2. 31 (aH, s),
3. 03-3. 24 (2H, m), 3. 76
(3H, s), 4. 53 (IHdd, J = 7
Hz, 10Hz), 7. 53 (IH, d, J
= 7Hz), 7. 1116(IH,t+J
= 7Hz), 8. 17 (IH, s) Reference Example 58 3-(1.3-dimethylvirazol-5-ylcarbonyl)amino-ε-caprolactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 183.0-184.0° IR(KBr)am': 3356, 3
224, 1667, 1639. 1542+515
1441. NMR (d.-DMSO) δ: l. 16{. 99
(6H, m), 2. 16 (3H, s), 3.
07-3. 26 (2H, m). 3. 95 (3
}1, s), 4. 51-4. 60 (18, m
). 6. 60 (IH, s), 7. 82-7.
88 (IH, m), 8. 10(IHd, J
= 7Hz). Reference Example 59: 3-(3-indolylacryloyl)amino-ε Kabukuchi lactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 198.0-199.0' IR (KBr) cm': 1670, 1
644, 1576, 1432, 1270,738
, NMR (d.-DMSO) δ: 1. 20-2. 0
0 (6tl, m), 3. 043. 25 (2H,
m), 4. 57 (IH, dd, J= 5Hz
, IOHz), 6. 88 (IH, d, J =
16Hz), 7. 10-7. 24 (3H, m
), 7. 41-7. 48 (IH, m). 7.
60 (IH, d, J = 16Hz), 7. 9
7-8. 07 (IH, m). Reference Example 60 3-(1.5-dimethylpyrazol-3-ylcarbonyl)amino-ε-cabrolactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 199. (1200.0' I R (K B r) am-' : 3390, 1
640, 1519, 1475, 1407, 137
2. 132g. NMR (d6-DMSO) δ: l. 17-2. 0
3 (6H, m), 2. 27 (3H, s), 3
．． 00-3. 28 (21L m), 3. 77 (
3H, s), 4. 43-4. 52(1[1,
m), 6. 40 (LH, s), 7. 92(I
H, d, J = 6Hz), 8. 01(LH,
L, J = 6Hz). Reference Example 61 3-(5,7-dimethylpyrazolo[1,51a-copyrimidin-3-ylcarponyl)amino-ε-monocarbolactam In the same manner as in Reference Example 17, the title compound was obtained.

Melting point 264.0-265.0' I R (K B r) cm-': 16g3, 1
645, 1562, 1514, 1436, 119
0. NMR (d6-DMso) δ: 1, 3g-2. 34(
6H, m), 2. 71 (3H, s), 2.
78 (3H, s), 3.26-3. 42 (2H,
m), 4. 81-4. 91 (IH, m),
6. 71 (18, s), 8. 60 (IH, s
). Reference Example 62 3-(2-biphenylcarbonyl)amino-ε Kabukuchi lactam The title compound was obtained in the same manner as in Reference Example 17.

Melting point 183.0-184.0° I R (K B r) cm-': 3250,
1678, 1645, 1541, 1476, 13
02,745. N M R ( C D C Q.) δ: 1. 07
-1. 40 (21!, +n). 1. 63-2.
01(4H, m)', 3. 15-3. 28(
2H, m). 4. 46-4. 55 (IH, m
), 5.98 (LH, br. s), 6. 75
(LH, br. s), 7. 30-7. 68(
9H. m) Reference Example 63 3-(1-Methylimidazol-5-yl acryloyl)amino-ε-monolactam The title compound was obtained in the same manner as in Reference Example 54.

Melting point 1 4 8.0- 1 5 0.0°r R (
KBr)am-': 1659, 1620,
1500, 1479, 1335, 1122. NMR (d, -DM'SO) δ: 1, 14-1. 96
(68, m), 3. 07-3. 22 (2H,
m). 3. 71 (3H, s), 4. 48-4
．． 59 (LH, i), 6. 72 (IH, d,
J = 15. 8Hz), 7. 28(LH,
d, J=15. 8Hz), 7. 31 (IH,
s), 7. '70 (ILs), 7. 84(
1}! , t, J = 6.0}Iz), 8. 0
4 (IH, d, J= 7, OHz). Example l 2-(4-chlorostyryl)-5.6,7.8-tetrahydride-4H-thiazolo[5.4-b]azebin 3-(
4-Chlorocinnamoyl)amino-ε-cabrolactam (11.0 g) and phosphorus pentasulfide (8.37 g) were added to 500 d of pyridine, and the mixture was refluxed for 1.5 hours.

After cooling, the reaction product was added to aqueous sodium bicarbonate and extracted with chloroform. The extracted layer was washed with water, dried, and the solvent was distilled off under wt pressure.

The residue was purified by 7 silica gel column chromatography and recrystallized from cyclohexane to give the title compound as crystals with a melting point of 188-189° (6.28 g, 57% yield).

I R (K Br) cm': 3274, 292
6, 1543. 14321355, 1090.
807 NMR (CDCQ3) δ: 1.50-1.98 (4}
1, m), 2.832.97 (2H, m), 3.0
7-3.16 (2H, m), 3.96 (IH, br.
s)6. 98 (2H, d, J-=IHz).
7. :{2(4H, d, J=IHz). Elemental analysis value C. , H , 5N, S Calculated value as CQ:
C, 61.95. H, 5.20; N, 9.63.
Actual value: C, 62.08; H, 5.08; N,
9.90. Example 2 2-(4-methkinstyryl)-5.6,7.8tetrahydro 4H-thiazolo[5.4-b]azepine 3-(4-methoxycinnamoyl)amino-ε The title compound was obtained from monocabrolactam and phosphorus pentasulfide (yield 34.8%). Melting point 13c
l-131' (recrystallized from cyclohexane) I R (K Br) cm-': 2914, 1601
, 1547, 1510, 1251, 117
5, 949. N M R (C D C l2s'
) δ: 1.67-1.84 (4H, m), 2.89
(2H, t, J= 6Hz), 3. 11 (2B
, t, J=5Hz), 3. 82 (3H, s)
, 6.88 (2H, d, J=9Hz). 6.98 (
2H, s), 7.41 (2H, d, J = 9Hz
) Elemental analysis value: Calculated value as Cl8H, 8N, OS:
c, a'y. io; H, 6J3; N, 9.7g.
Actual value: C, 67.29; H, 6.23; N,
9.70. Example 3 2-Styryl-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine By the same method as in Example 1, 3-cinnamoylamino-epsilon lactam and pentasulfide were prepared. The title compound was obtained from phosphorus (yield 40.3%)
. Melting point 169-170° (recrystallized from cyclohexane)
．． IR(KBr)am-': 3220, 291
8, 1523, 1439, 1362. 1269.
93+11. NMR (CDC 123)
δ: 1.50-1.93 (4H, m), 2.802
．． 92 (2H, m), 3.01-3.12 (2H, m
), 7.05 (2H.s), 7, 23-7. 59(
5H, m). Elemental analysis value: C,. H,. Calculated value as N, S: C,? 0.27; H, 6.29;
N, 10.93. Actual value: C, 70.53; H,
6.30; N, 10.94. Example 4 2-(1-phenylbutyryl)"5,6,7.8tetrahydride-4H-thiazolo[5.4-b]azepine By the same method as in Example 1, 3-(2-phenylbutyryl) The title compound was obtained from amino-ε-cabrolactam and phosphorus pentasulfide (yield 31.9%).

Melting point: 106-107° (recrystallized from hexane). r R
(KBr)am-': 3244, 2924. 1
474, 1261. 701NMR (CD cI
2s) δ: 0.89 (3H, t, J=7Hz),
1.38-2. 38 (6H, m), 2. 7
7-3. 05 (4H, n+3. 3. 32 (I
H, br. s), 4. 93 (18, t,
J=8Hz), 7. 28 (5H, s). Elemental analysis value: C 1sH , oN t Calculated value as S: C,? 0.55; H, 7,40; N, 10.
28. Actual value: C, 70.45; H, 7.27.
N, 10.15 Example 5 2-(4-methoxyphenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azepine hydrochloride By the same method as Example 1, 3-(4-Methoxybenzoyl)amino-ε-caprolactam was reacted with phosphorus pentasulfide, and after purification, the title compound was converted into a hydrochloride salt (yield: 9.6%). Melting point: 177,178° (recrystallized from methanol/ether). IR(KBr)cm-': 1
605, 1533, 1292, 1281, 126
3, 1190, 832. NMR (CDCl23)δ: 1.50-1.9
0 (4H, m), 3.033. 30 (4H, o+
), 3, 80 (3H, s). 6.89 (2H.d,
J=9Hz), 7. 98(2}1, d, J= 9
Hz). Elemental analysis value: ． C,4H,. N,S-HC
Calculated value as C: C, 56.65. H, 5.77
．． N, 9.44; C Q, 11. 94. Actual value: C, 56.48; H, 5, 87; N,
9.40; CCI2.17? Example 6 2-(4-methylstyryl)-5.6,7.8-tetrahydride-48-thiazolo[5.4-bl azebin By the same method as in Example 1, 3-(4-methylstyryl)-5.6,7.8-tetrahydride The title compound was obtained from cinnamoyl)amino-ε-cabrolactam and phosphorus pentasulfide (yield 49.5%). Melting point 166-16
7° (recrystallized from cyclohexane)] R (KBr) cm"": 2920. 1546.
143g, 1355, 1270, 955■ 8
02. NMR(CDC&3)δ: 1.51-1.9
5 (4H, m), 2J5 (3}1, s), 2.80
-2.93 (2H, m), 3.01-3.15 (2H
, m), 7.05 (2H, s), 7.15 (2H, d
, J=8}1z), 7.38(2H,d,J=8Hz
) Elemental analysis value・C. ．． H. ．． Calculated as N2S: C, 71.07; H, 6,71; N, 10.
36. Actual value: C, 71.02; H, 6.57;
N, 10.23. Example 7 2-(4-ethoxystyryl)-5.6,7.8tetrahydro 4H-thiazolo[5.4-b]azepine 3-(4-ethoxysonnamoyl)amino The title compound was obtained from ε-cabrolactam and phosphorus pentasulfide (yield 426%). Melting point 159i
60° (recrystallized from cyclohexane) IR(KBr)Cm-': 2924, 1601,
1550, 1510, 1268 1244, 1
176. NMR (CDCff.) δ: 1.40 (3H, t, J
=7Hz), 1.60L. 93 (41m), 2.
89 (2R, dd, J==4Hz, 6Hz), 3.1
1 (2H, t, J=5Hz), 4.03 (2H, q,
J=7Hz), 6.84(2Hd, J=9Hz),
6.96 (2H, s), 7.36 (2H, d, J=
9tlz). Elemental analysis value: CI78 20Nt
o Calculated as S: C, 67.97; H, 6.
71: N, 9.32. Actual value: C, 68.06.
H, 6.63. N, 9.45 Example 8 2-(4-isoprobylstyryl)-5.6,7.8-
Tetrahydro-4H-thiazolo[5.4-b]azebinSimilarly to Example 1, the title compound was obtained from 3-(4-isopropyl/annamoyl)amino-e-monocablactam and phosphorus pentasulfide (harvested rate 47.8%). Melting point 148-
149° T R (K Br) c+n-': 3258. 295
0, 2922, 1547, 143g, l357,
1266. N M R (C D C Q3) δ: 1.23 (6
H, d, J=7Hz), 1.611. 93 (4L
m), 2. 72-1 18 (5H, n+), 7
．． 19 (2H. d, J=9Hz), 7.20 (
2H, s), 7.38 (2H, d, J=9Hz). Elemental analysis value: C,. Calculated value as H,,N2S C,
72.44; H, 7.43. N, 9.39. Actual measurement value 2 C, 72.11. H, 7.34. N, 9.35
．． Practical example 9 2-E4-(4-methoxyphenyl)butadienyl]
-5,6,7,8-tetrahydro-4H-thiazolo I5
．． 4-bj acepine In the same manner as in Example 1, the title compound was obtained from lc5-(4-methoxyphenyl)pentadienoyl]amino-ε-caprolactam and phosphorus pentasulfide (yield 19.4%).
. Melting point 140-142° (recrystallized from cyclohexane)
．． r R(KBr)am-': 1542, 1509,
1441. 136g, 1251, 1172,
986. NMR (CDCQ3) δ: 1.52-1.93(4}
1, m), 2.802. 92 (2H.m), 3
．． 03-3. 14 (2H, m), 3. 80(
3H, s), 6.43-6.76 (4H, m), 6
．． 83 (2H, d, J=9Hz), 7.35 (2H,
d, J-9Hz) Elemental analysis value: C,. H. Calculated values as N, O S: C, 69, 20; H, 6.45; N,
8.97 Actual value: C, 6g. 90; H, 6.62
; N, 8.80. Example 10 2-(4-I/bropoxystyryl)-5.6,7.
8-tetrahydride-4H-thiazolo[5.4-bl azebin] In the same manner as in Example 1, the title compound was obtained from 3-(4-isopropoxycinnamoyl)amino-ε-cabrolactam and phosphorus pentasulfide ( yield 35.5%). melting point 16
1-162° (recrystallized from cyclohexane) IR(KBr)cm-': 3266, 1547,
1509, 1442, 1359, 1239.
943 NMR (CDC(3)δ: 1.30 (6H, d, J=
6Hz), 1.58-1.92 (4H, m), 2.
80-2.95 (2}1, m), 3.03-3. 1
3 (2H, m), 4. 53(18, septet
, J=6Hz), 6. 82 (2H, J=9
Hz) 6.92 (2H, s), 734 (2H, d, J
=9) {z). Elemental analysis value: C 18H 22N
Calculated value as to S: C, 6g. 75; H, 7
．． 05; N, 8.91. Actual value: C, 69.10
; H, 7.12; N, 9.01. Example 11 2-(3.5-t-butyl-4-hydroxystyryl)-5.6,7.8-tetrahydro-4Hthiazolo[
5.1-b] Acepine oxalate In the same manner as in Example 1, i(3,5-di-t-butyl-4-hydroxycinnamoyl)amino epsilon-kabuguchi lactam and phosphorus pentasulfide were reacted, and after purification, 7 The title compound was obtained by neutralizing with uric acid (yield 37.4%). Melting point 205-206°IR
(KBr)cm': 29511! , 1729,
1592, 1437, 1374, 1237
．． 120g, NMR (CDCIδ: 1.40
(18H, s), 1. 53-1. 83 (4H
, +n), 2.60-2.76(2[{,m),
2.86-3.03 (2H, m)6. 94 (2H,
s), 7. 28 (2H, s). Elemental analysis value:
C, 3H3, N2OS-C. Calculated value as H20, .H,O: C, 60.95; H. 7.37; N,
5.69. Actual value: C, 60, 97. H, 7.3
0: N, 5.72 Example 12 2-(2-methoxystyryl)-5.6,7.8=tetrahydride-4H-thiazolo[5.4-b]azevin oxalate Same as Example 1. , 3-(2-methoxynnnamoyl)amino-ε-monocarboxylic lactam was reacted with phosphorus pentasulfide, and after purification, the title compound was obtained by neutralizing with phosphoric acid (
Yield: 36.7%).

Melting point 171-172° IR(KBr) cm-': 1592, 1519.
1378, 1352, 1253. 1207. NMR (d.-DMSO) δ: l. 33-1.
82 (48, m). 2. 68-2. 80 (2H,
m), 2. 90-3. 02 (2H, m),
3. 84 (3H, s), 6. 83-7.6
3 (4H, m), 7. 15 (2H, s). Elemental analysis value: C,. H,. N, OS-C, H. O.・
0. Calculated value as 3 H t○: C, 56.62; H, 5.44; N,
7.34. Actual value: C, 56.67; H, 5.1
3; N, 7.14. Example 13 2'-(3.4-methylenedioxystyryl)-5.6
,7.8-tetrahydro-4H-thiazolo[5,4b]
Azevin/hydrochloride In the same manner as in Example 1, 3-(3,4-methylenecyoxycinnamoyl)amino-epsilon-capsulactam and phosphorus pentasulfide were reacted, and after purification, the product was neutralized with hydrochloric acid. The title compound was obtained (yield 42.3%).

Melting point 196-197° (recrystallized from chloroform-ether). IR(KBr)am"-': 1597. 1505
．． 1487, 1449, 1356, 1256.

NMR (d.-DMSO) δ: 1.50-1, 91
(4H, m), 2. 75-2. 93 (2H, m
), 2. 99-3. 15 (2H, m),
6. 06 (2H, s), 6. 90-7. 55
(5}1, m). Elemental analysis values: C,,H,. N,
O,S-HCf2-0.3H! Calculated value as O: C, 56.15; H, 5.18; N,
8.19. Actual value: C, 56.3g. H, 4.8
9; N, 8.22. Example 14 2-(α-phenylstyryl)-5.6,7.8tetrahydro 4H-thiazolo[5.4-b]azevin hydrochloride In the same manner as in Example 1, 3-(α-phenylcinnamate) The title compound was obtained by reacting amino-ε-cabrolactam with phosphorus pentasulfide and neutralizing the purified product with hydrogen chloride (yield: 13.5%).

Melting point 188-189° IR(KBr)cm-': 3180, 1595
, 1506, 1490, 1352, 693. N M R (ds D M SO ) δ: 1.
47-1. 90 (4H, m), 2.83-3.1
1 (4H.m). 6.90-7.56 (IIH, m)
Elemental analysis value' Ct+HtoNtS @HC(1・
Calculated value as 0.2H, ○: C, 67.71; H, 5.79; N,
7.52. Actual value: C, 67, 79. H, 5.6
8. N, 7.53. Example 15 2-(2,3.4-trimethoxystyryl)-5,
6.7.8-Tetrahydro 4H-thiazolo[5,4b
]Azepine oxalate In the same manner as in Example 1, 3-(2,3.4-}rimethoxycinnamoyl)amino-ε-monolactam and phosphorus pentasulfide were reacted, and after purification, the product was dissolved in oxalic acid. The title compound is obtained (yield 42.7%). Melting point 145-1
46° (recrystallized from ethyl acetate) I R(K Br) cm-': 1742, 1588
, 1495, 1283, 1203. 1108.
1098 NMR (d.-DMSO) δ: 1.56-1.69 (
4H, m), 2. 73 (2H, t, J= 5Hz
), 2. 94-2. 99 (2H, m), 3,
76 (3H, s), 3. 80 (3H, s),
3. 82 (3H, s). 6.83 (IH, d,
J-9Hz), 7. 06 (2H, s), 7.
39 (IH, d, J = 9Hz). Elemental analysis value:
C +sH ttN to 3S-C, Hto-
・Calculated value as 0.5H20: C, 53, 92: H, 5.66; N,
6.29. Actual value: C, 53.66; H, 5.4
1; N, 6.14. Example 16 2-(3.4-dimethoxystyryl)-5.6.7.8
-tetrahydro4H-thiazolo[5.4-b]aze・
Pin hydrochloride In the same manner as in Example 1, 3-(3,4-dimethoxycinnamoyl)amino-ε-monocabactam and phosphorus pentasulfide were reacted, and after purification, the product was neutralized with hydrogen chloride, and the title A compound was obtained (yield 23.7%). Melting point 159-160° (recrystallized from chloroform-ether). IR(KBr)cm-': 343g, 3220
, 1609, 1593, 1516. 126g. NMR (de-DMSO) δ: 1. 62-1. 7
3 (4H, m), 2. 80-2. 85 (2H,
m), 3. 04-3. 09 (2H, m), 3
, 80 (3Hs), 3.82 (3H,s), 7.0
1 (LH, d, J=8Hz), 7.17 (1B, dd
, J=8Hz, 2Hz). 7.26 (IH, d, J=
2Hz), 7.24 (IH, d, J=16Hz),
7.43 (IH, d, J=16Hz), elemental analysis value:
C 17H 2oN 20 zs ” H C(l
'Calculated value as 1.3Hto: C, 54, 26; H, 6J2. N,7
．． 44. Actual value: C, 54.48: H, 6.31
; N, 7.46. Example 17 2-(9-decenyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine undecylenic acid (15 g) was dissolved in tetrahydrofuran with 15.8 g of 1,1 After adding '-carbonyldiimidazole and stirring at room temperature for 15 minutes, 10.4 g of 3-amino-ε-cabrolactam was added and the mixture was stirred at room temperature for 5 hours. Next, the solvent was distilled off under reduced pressure, and the obtained crude 1-(10-undecemyl)amino-ε-cabrolactam and 18.1 g of phosphorus pentasulfide were
00d of pyridine and stirred under reflux for 1 hour. After cooling, the reaction product was added to saturated aqueous sodium bicarbonate solution and extracted with chloroform. The extracted layer was washed with water, dried, and the solvent was distilled off under reduced pressure.

The residue was purified by silica gel column chromatography and subsequently converted to oxalate. Recrystallized from isobrobyl ether7
．． 7g (24.7%) of the title compound was obtained. Melting point 94-
95°C, IR(KBr)cm-': 2928,
2854, 1607, 1528, 1404, 12
79, 720. NMR (CD (d!s) δ: 1.30 (12H, br
．． s). 1.50-2. 16 (6H, m). 2
．． 78-3. 17 (6H, m), 4. 89-
5. 07 (2H, m), 5. 58-6. 03(
IH, m). Elemental analysis values: C,,H,. N. S
-C. H. O. Calculated value: C, 59.66;
H, 7.90: N, 7J2. Actual value: C, 59
．． 78; H, 8.13; N, 7.28. Example 18 2-(2.6-difluorophenyl)-5.6. ,7.
8-Tetrahydro 4H-thiazolo[5.4-b coazepine To a solution of 2,6-difluorobenzoic acid (12 g) in tetrahydro (200 m) was added 14.8 g of 1.1'-carbonyldiimidazole and the mixture was stirred at room temperature for 15 minutes. After stirring, 9.
73 g of 3-amino-ε-monolactam was added and stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure and the residue was washed with methylene chloride to give 13.5 g of 3 as crude crystals.
-(2,6-difluorobenzoyl)amino-ε-cabrolactam was obtained. The crude crystals were added to 200-g of pyridine together with 8.96 g of phosphorus pentasulfide, and the mixture was stirred under reflux for 24 hours. After cooling, pyridine was distilled off, saturated aqueous sodium bicarbonate was added to the residue, and the mixture was extracted with chloroform. The extracted layer was washed with water, dried, and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel followed by recrystallization from methylene chloride isobutyl ether afforded the title compound in 3.1
9g (23.8%) was obtained.

Melting point 141144° I R (K Br) cm': 3230, 2912
, 1467, 1355, 1013 990,
783. N M R (C D C c, i) δ: 1.50-
2.00 (4H, m), 2.913. 25 (4H,
m), 6. 78-7. 45 (3H, m). Elemental analysis value: Calculated value as C, 3H,, N, SF2:
C, 5g. 63; H, 4.54; N, 10.5
2. Actual value: C, 5g. 72; H, 4.52.
N, 10.32. Example 19 2-(2,4-difluorophenyl)-5.6,7,8
-Tetrahydro-4H-thiazolo[5.4-b]azepine In a similar manner to Example 18, the title compound was obtained from 2,4-difluorobenzoic acid, 3-amino-epsilon-cabulactam and phosphorus pentasulfide. (yield 43.7%). melting point 10
5.5-107.0° (recrystallized from cyclohexane). IR(KBr)cn+-': 1545, 150
4, 1479, 1436, 1351, 1095. NMR (CD cc3) δ: 1.50-1.98
(4H, m), 2, 903. 16 (4H, m),
3. 76 (IH, br. s), 6. 73-
7. 03(28, m), 8, 03-8. 30 (I
H, m). Elemental analysis values: C, 3H, 2N, SF,
Calculated values as: C, 58.63; H, 4.54;
N, 10.52. Actual value: C, 58.68; H
, 4.47; N, 10.59, Example 20 2-(3,4-dichlorostyryl)-5.6,7.8tetrahydro-4H-thiazoloC5,4-b]azebin Same as Example 18 In general, the title compound was obtained from 3,4-dichlorocinnamic acid, 3-amino-epsilon lactam and phosphorus pentasulfide.

Melting point 191-192° (recrystallized from Improbanol)
．． IR(KBr)cm-': 3276, 2922
, 1539. 142g, 1355. 940 NMR (CDCC.) δ: 1. 65-1. 72(
2H, m), 1. 801.88 (28, m),
2.92 (2H, t, J=6Hz), 3.13 (2H
, t, J-5Hz), 6.93 (IH, d, J=16
Hz), 7.10 (IH, d, J=16Hz), 7
．． 28 (IH, dd, J=8Hz, 2Hz), 7, 4
0 (IH, d, J8Hz), 7, 52 (IH,
d, J = 2}1z). Elemental analysis value: C,,H
,,N. Calculated value as SCl2: C, 55.39
．． H, 4.34: N, 8.61. Actual value: C,
55.22; H, 4.26; N, 8.91. Example 2l 2-(4-phenylbutadienyl)-5.6,7.8-
Tetrahydro-4H-thiazolo[5.4-b]azepine The title compound is obtained from 5-phenyl-2,4-pentadienoic acid, 3-amino-epsilon-cabrolactam and phosphorous pentasulfide in the same manner as in Example 18. (yield 31.9%)
. Melting point 156-157° (recrystallized from cyclohegyusan)
．． IR(KBr)cm-': 3278, 2914,
1547, 1509, 1495, 1369.
980. NMR (CDC.) δ: 1.53-1.92 (4H
, m), 2, 802.92 (2H, n+), 3.0
3-3.16 (2H, m), 6.70-6.87 (4
H, m), 7. 18-7. 46 (5H, m).
Elemental analysis values: Calculated values as C,,H,,N,S: C, 72.30; H, 6.42; N, 9.
92 actual value: C, 72.12; H, 6.35.
N, 9.66. Example 22 2-(4-nitrostyryl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azepine 4-nitrocinnamic acid, 3 The title compound was obtained from -amino-epsilon-cabrolactam and phosphorus pentasulfide (yield 20.2%).

Melting point 219-220° (recrystallized from Improbanol)
．． IR(KBr)cn+-': 327g, 1595
, 1531, 1514, 1435, 1356.
133g, 1270, 936. NMR(d
．． -DMS○) δ: 1.65 (4B, br.s),
2.702. 83 (2H, m), 2. 9
3-3. 04(2}1, m), 7. 10(I
H, d, J=16Hz), 7.46(IH, d,
J2 16Hz). 7.87 (2H, d, J9Hz)
, 8.21 (2H, d, J=9Hz) elemental analysis value:
Calculated value as C, 5H, 5N30, S C, 59.
78; H, 5.02; N, 13.94. Actual value:
C, 59.49; H, 4.88; N, 13.61
Example 23 2-(2-fluorophenyl)-5.6,7.8tetrahydro4H-thiazolo[5.4-b]acevin 200M methylene chloride with 3-amino-epsilon capulactam (11.0 g) Triethylamine (15.7d
) was added thereto, and a solution of 2-fluorobenzoyl chloride (15.0 g) in methylene chloride (30d) was added dropwise under stirring with water cooling. After the dropwise addition was completed, the mixture was stirred at room temperature for 1.5 hours, and the precipitated crystals were filtered. The crude crystals of 3-(2-fluorohenzoyl)amino-ε monolactam were obtained. Add this and phosphorus pentasulfide (165.g) to 200d of pyridine,
The mixture was stirred under reflux for 12 hours. After cooling, pyricin was distilled off, saturated aqueous sodium bicarbonate was added to the residue, and the mixture was extracted with chloroform. The extracted layer was washed with water and dried, and then the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel, followed by recrystallization from ether to yield 4.55 g (24.7%) of the title compound. Melting point 115-116°IR(KBr)
cm-': 3236, 2944, 2916, 1
496, 1453, 1371, 1357, 110
2, 757. NMR (CDC(23)δ: 1.36
-2.03 (4H, m), 2.923, 20 (48,
m), 3.66 (IH, br. s), 6.93
-7. 32 (3H, m)8. 08-8. 27(
LH, m). Elemental analysis value C,. H. N,S
Calculated value as F: C, 62.88. H, 5.28
; N, 11.28 Actual value: C, 62.87; H
, 5.14; N, 11.36 Example 24 2-(4-nitrophenyl)-5.6,7.8-tetrahydro-4H-thiazoloC5,4-b]azepine By the same method as Example 23, The title compound was obtained from 4-nitropenzoyl chloride, 3-amino-ε-cabrolactam and phosphorous pentasulfide (yield 448%). Melting point 15
9-160° (recrystallized from cyclohexane). IR(KBr)cm"": 2920, 1592,
1534, 1510, 1490, 1430, 1
355. 13031103. NMR (CDC(3)δ l. 49-1. 96(4
H, m). 2,903.00 (2H, m). 3
．． 10-3.20 (2H, m), 4.14 (IH, b
r. s), 7.86 (2}1, d, J=9Hz).
8.21 (2H, d, J=9Hz). Elemental analysis value・C
,3H ,3N Calculated value as 30,S: C,5
6.71; H, 4.76; N, 15.26. Actual measurements: C, 56.90; H, 4.69; N, 15.
39. Example 25 2-(3-nitrophenyl)-5.6.7.8-tetrahydride-4H-thiazoloE5.4-b]azepine By the same method as in Example 23, 3-nitropenzoyl chloride, 3- The title compound was obtained from amino-ε-cabrolactam and phosphorus pentasulfide (yield 457%). melting point 16
8-169 (recrystallized from chloroform-isobrobyl ether). IR(KBr)cm': 29
20. 1520, 1450, 1370,1
345, 1300, 1270. 735N
M R (C D C Q3) δ: 1.49-
1.99 (4H, m), 2.93 (2H, dd,
J=4Hz, 6Hz), 3.06-3.16
(2H, m). 3.834. 19 (IH, br
．． s), 7. 50 (IH, t, J= 8H
z), 8. 008. 16 (2H, m),
8. 57 (IH, t, J = 2Hz) Elemental analysis value: Calculated value as C 131"1 13N 3o ts: C, 56,71; H, 4.76; N, 15
, 26. Actual value: C, 56.66; H, 4.71
; N, 15.10. Example 26 2-phenyl-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]acevin By the same method as in Example 23, penzoyl chloride, 3-amino-ε-cabrolactam and The title compound was obtained from phosphorus sulfide (yield 44.5%). Melting point 1 2 2.0 - 1 2 3
．． 5° (recrystallized from ethanol water). IR(KBr)cm': 3228, 3004
．． 2926, 1564, 1524 1502
1462. 13701270. 757 NMR (C D Cl!3) δ: 1.50-1.
96 (4H, m), 2.893. 15<4H,
m), 3. 56 ([1, br. s), 7
．． 26-7. 48 (3H, m), 7.69-
7.80 (2H, m). Elemental analysis value: C, 3H
Calculated value as I4N tS: C, 67.79; H
', 6, 13; N, 12.16 Actual value: C, 67
．． 55. H, 6.04; N, 12.17. Example 2
7 2-ethyl-5.6,7.8-tetrahydro-48-thiazolo[5,4. -b] Azepine oxalate In the same manner as in Example 23, propionyl bromide, 3-amino-ε-monocapsulactam and phosphorus pentasulfide are reacted,
After purification, the title compound was obtained by neutralizing with sulfuric acid (
Yield 34. 0%).

Melting point 145-146° (recrystallized from isobrobanol) IR(KBr)cm': 2930, 1720
, 1600, 1520, 1370, 1275,
1200. 720NMR(d.-DMSO)6i
: 1.16 (3H, t, J=7Hz) 1.32-1
．． 81 (48, m), 2,464.73 (4H, m)
, 2.812. 92 (2H, II1) Elemental analysis value: C, H,, N, S-C, calculated value as H204: C, 4g. 52. H. 5.92; N
, 10.29 Actual value: C, 48.52: H, 5.
98; N, 10.18 Example 28 2-styryl-5.6,7.8-tetrahydro 4H-
Thiazolo [5.4-b Coazevin oxalate By a method similar to Example 23, cinnamoyl chloride, 3
-Amino-ε monocapsulactam and phosphorus pentasulfide were reacted, purified and neutralized with oxalic acid to obtain the title compound (yield 53%).

Melting point 18f3-189° (recrystallized from ether) I R
(KBr)cm-': 3280. 2920, 16
10, 1590, 1520. 13g0, 1350
．． 1190NMR (CDCC3) δ: 1.46-
1.96 (4H, ml) 2.773.17 (4H, m)
, 6.93 (IH, d, J=16Hz), 7.15
(IH, dJ=16Hz), 7. 19-7. 6
0 (5H, m). Elemental analysis value 2 CI5HllIN,S
Calculated value as -C2I4,o4・0.5H,O: C,57,45. H, 5.39; N,
7.88. Actual value: C, 57.46; H, 5, 13
; N, 7.91 Examples 2-2-hebutadene-5.6,7.8-tetrahydride-4
8-thiazolo[5.4-b]azebin The title compound was obtained from stearoyl chloride, 3-amino-epsilon-caprolactam and phosphorus pentasulfide by a method similar to Example 23 (
yield 26.1%).

Melting point 7 5-7 6° (recrystallized from methanol). I
R(KBr)cm'-': 3230, 2930.
2g50, 1465, 1265. NMR (CDC(3)δ: 0.88 (3H, t, J=
5Hz), 1.26 (301{,br.s), 1.
47-1.90 (4H.m), 2.67-2.90 (
4H, m), 2.98-3.10 (2H, m) Elemental analysis value 2 Calculated value as C 24H 44N 2S:
C, 73.41; H, +1.29; N, 7.13.
Actual value: C, 73.46; H, 11.00. N
,7Jl Example 30 2-(2-naphthyl)-5.6,7.8-tetrahydrogen-4H-thiazolo[5.4-b]azepine Example 23
Naphthoyl chloride, 3-amino-ε
The title compound was obtained from monocabrolactam and phosphorus pentasulfide (42.9% yield).

Melting point 171-172°IR(KBr)cm-”: 3442, 3240
, 2920, 1529, 1508. 1371. NMR (CDCl23) δ: 1.56-2.00 (4
H, ml 2, 923.18 (4H, m), 7. {5
-8.18 (7}1,m) Elemental analysis value: C,7H
Calculated value as 1gN 2S: C, 72.82;
H, 5.75; N, 9.99. Actual value: C, 72
．． 78; H, 5.87; N, 9.79 Example 3l 2-(2-chenyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-bl azepine Same method as Example 23 2-Thenoyl chloride, 3-aminoε
The title compound was obtained from monocafrolactam and phosphorous pentasulfide (yield 59%).

Melting point 123-124° IR (KBr) cm-': 3240, 2916,
1554. 15191415. 1370 NMR (CDC(!3)δ: 1.47-1.95(4
H, m), 2.83-2. 95 (2H, m),
3. 00-3. 11 (2H, m), 3.
65 (IH.br.s)6. 90-7. 00(
IH, m), 7. 19-7. 23 (2H,
m). Elemental analysis value: C + + H, t N t
Calculated value as S2: C, 55.90. H, 5
．． 12; N, 11.85. Actual value: C, 55.8
0; }1,5.13; N,11.83. Example 32 1-(4-Methyl-1-piperacinyl)acetyl 2-phenyl-5,6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine 2-phenyl-5.6,7.8
-Tetrahydro 4H-thiazolo[5.4-b]azevin (3.0g) and triethylamine (3.6ml2)
was added to the methylene chloride of the ioo mosquito, and stirred under water cooling for 2 hours.
．． 2 g of chloroacetyl chloride was added dropwise. After stirring at room temperature for 30 minutes, the solvent was distilled off under reduced pressure, and the residue was extracted with chloroform. The extracted layer was washed with saturated sodium bicarbonate solution and water, and then dried over anhydrous sodium sulfate. 1.9 g of the crude material (4.0 g) obtained by distilling off the solvent under reduced pressure was added to 2i tetrahydrofuran together with 2.6 d of triethylamine, and then N-methylpiperazine (1.4 d ) and stirred at room temperature for 5 hours. The reaction solution was concentrated and extracted with ether. The extracted layer was washed with water, dried, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, converted to hydrochloride, and recrystallized from imbropanol-ether to give 1.66 g (
56%) of the title compound was obtained. Melting point 195-197
°IR(KBr)cm-': 3340, 2560
, 1660, 1460, 1370. NMR (CDCf2ff) δ: 1.50-2.15 (
4H, m), 2.26 (3Hs), 2. 33-2
．． 76 (8H, m), 2. 83-3. 12(
2H, m), 3. 21 (2H, s), 3.
62-3. 86 (2H, m), 7. 30-7.
54 (3H, m), 7. 80-8. 00 (2H.
m). Elemental analysis value: C2oHteN-OS
・Calculated value as 2HCI2・2H,O: C, 50.10; H, 6.73; N,
11.69. Actual value: C, 49. f! 13;H,
6.71; N, 11.67 Example 33 4-morpholinoacetyl-2-phenyl-5,6,7.
8-Tetrahydro-4H-thiazolo[5.4b]acepine hydrochloride In the same manner as in Example 32, 2-phenyl-5,6.7.
The title compound was obtained from 8-tetrahydro-4H-thiazolo[5,4-b]azepine, chloroacetyl chloride and morpholine (yield 34.4%).

Melting point 208-211 (recrystallized from inbrobanol ether) IR(KBr)cm-': 2490, 16g0
, 1460. 1450, 1365. 1120. NMR (CDCC3) δ: 1.53-2.20 (4H
, m), 2.40-2. 70 (4H, m), 2
．． 83-3. 12 (2H, m). 3. 20(
2B, s), 3. 53-3. 94 (6H, m)
, 7. 30-7. 53 (3H, m), 7.
807, 911t (2H, m). Elemental analysis value: C+sH, 3N. O. S-HCg-0
．． Calculated value as 5HtO: C, 56.64; H, 6.25; N,
10.43. Actual value: C, 56.40; H, 6.
{2; N. 10.49. Example 34 4-E3-(4-Methyl-1-biverazinyl)propionyl 2-2-phenyl-5,6,7.8-tetrahydride-4H-thiazolo E5.4-bj azevin゜fumarate Example 32 Similarly, 2-phenyl-5,6,7.
The title compound was obtained from 8-tetrahydro-4H-thiazolo[5.4-b]azevin, 3-chloroprobionyl chloride, N-methylbiverazine and fumaric acid (yield: 35
%). Melting point 201202° (recrystallized from isopropanol). IR(KBr)cn+-': 2930, 1
660, 1540, 1450, 1380 117
0. N M R (C D C (!3) δ: 1.54-
2.20 (4H, m1 2.23 (3Hs). 2.
41 (8H.m), 2. 59-2. 76 (48
, m), 2. 88-3. 13 (2B, m),
3. 60-3. 94 (2H.m), 7. 3
3-7. 55 (3H, m), 7. 80-7. 9
6 (2H, m). Elemental analysis value: C tlH zs
N -O S' C 4H 40. Calculated value: C, 59.98: H, 6.44; N,
11.19. Actual value: C, 59.82; H, 6.
58; N, 11.16, Example 35 1-(3-morpholinopropionyl)-2-phenyl 5, 6, 7. 8-Tetrahydro-4H-thiazolo[5.4-b]azepine hydrochloride In the same manner as in Example 32, 2-phenyl-5,6,7.
The title compound was obtained from 8-tetrahydro-4H-thiazolo[5,4b]azevin, 3-chloropropyl hydrochloride, morpholine, and hydrogen chloride (yield: 43%).

Melting point 184-186° (recrystallized from isoprobanol) IR(KBr)cm': 3450, 2920
, 2370, 1640, 1455. 1430. NMR (CDC & 3) δ: 1.52-2.19 (4H
, m), 2.292.51 (4H, m). 2.60
-2.73 (4H, m), 2.86-3.10 (2H
, m), 3.50-3.88 (6H m), 7.3
2-7.53 (38, m), 7.81-7. 97(
2H, m) Elemental analysis value: C 208 25N 30 2S'
Calculated value as H C Q '0 5H20: C, 57.61・H. 6.53; N, 1
0.0g. Actual value: C, 57.77. H, 6.4
9. N, 9.98 Example 36. 1[3-(3.4-dimethoxyphetinole)aminopropionyl]-2-phenyl-5,6.7.8tetrahydro-4H-thiazolo[5.4-b]azepine fumarate Same as Example 32. and 2-phenyl-5,6,7.
The title compound was obtained from 8-tetorahydride-4H-thiazolo[5,4b]azepine, chloropropionyl chloride, β-(3,4-dimethoxyphenyl)ethylamine and fumaric acid (yield 42%).

Melting point 143-144° (recrystallized from ether) I R
(KBr)cm"-': 1710, 1660
, 1342, 1320, 1405, 1255. NMR(CDC(13')δ: 1.50-
2.13 (5H, m), 2.463.20 (IOH,
m), 3.55-4.00 (2H, m), 4.81
(3H, s), 4, 83 (38, s), 6. 75
(3H, br.s), 7. 33-7. 98(
3H, m), 7.80-7.98 (2H, m). Elemental analysis value: C 211H 3+N Go 3S'
Calculated value as C 4H 40 4・0.5H,0: C. 61.00; H, 6.14; N,
7.11. Actual value: C. 61. l7; H, 5.9
4; N, 6.84 Example 37 4-(4-Methyl-1-piveracinyl)acetyl 2-styryl-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine hydrochloride implementation Similarly to Example 32, 2-styryl-5,6,7.8-tetrahydro-4
The title compound was obtained from H-thiazolo[5,4-b]azepine, chloroacetyl chloride, N-methylbiverazine and hydrogen chloride (yield 23%). Melting point 182-184°
(Recrystallized from methanol/ether). IR(KBr)cm-': 3400, 1670
, 1610, 1440, 1410. NMR(d,-DMSO)δ l. 36-2. 13
(4H.m), 2. 72-3. 02 (5H, m
), 3. 27 (2H, s), 3. 36-4.
00 (IOH, m), 7. 27-7. 75 (7
H, m). Elemental analysis value: C2, H2. N,
OS・3HCQ・t. Calculated value as 3Hto: C, 49.92; H, 6.40; N,
10.58. Actual value: C, 49.97; H, 6.
57: N, 10.59. Example 38 4-I(3.4-dimethoquinfetinole)ami/acetinoleni-2-styrinole-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azevin hydrochloride Example 32 Similarly, 2-styryl-56.7.8
The title compound was obtained from -tetrahydride-4H-thiazolo[5.4b]azevin, chloroacetyl chloride, β-(3.4 dimethoxyphenyl)ethylamine and hydrogen chloride (yield 29%).

Melting point 170-172° IR (KBr) cm-': 1660, 1600,
1520, 1410, 1255. 1235. NMR (CDCff3) δ: 1.49-2.11 (5
1{, m), 2.603.06 (6H, m), 3.
12 (2H, s), 3.56-3.80 (2H, n+
). 3, 82 (3H, s), 3. 84 (3B,
s), 6. 74 (3H, br. s), 7. 2
6-7. 41 (7H, m). Elemental analysis value: C,
7H3,N30,s・3HCC・0 Calculated value as 4H20: C, 58.14; H, 6.11; N,
7.53;S, 5.75. Actual value: C, 58. 23; H, 6, 0
2; N, 7.47S, 6.01. Example 39 2-(2-fluorophenyl)-4-[3-(N-(4fluorophenyl)piperazino)flopionyl]5,6.7
．． 8-Tetrahydro-4H-thiazolo[5,4-b]azebin hydrochloride In the same manner as in Example 32, 2-(2-fluorophenyl)
-5.6,7.8-tetrahydride-4H-thiazolo[5
, 4-b] azepine, 3-chloropionyl chloride, N
The title compound was obtained from mono(4-fluorophenyl)piperazine and hydrogen chloride (yield 51%). Melting point 131-
132° I R (K Br) cm': 33, 50, 164
5, 1509, 1443, 1410 1229. NMR(d,-DMSO) δ: 1.50-2.10(
4H, m), 2. 89-3. 10 (2H, m).
3. 30-4. 00 (14H, m), 6.
957. 63 (7H, m), 8. 05-8.
30 (IH, m) Elemental analysis value' C 28H 2B
Calculated value as N40SF2・3HCi2・0.9H20 C, 51.35; H, 5.44; N, 9.
21:S, 5.27. CC, 17.49 Actual subvalue: C, 51.39; H, 5.44; N,
9.16;S, 5.27. C(,17.14 Example 40 2-phenyl-4-stearoyl-5,6,7.8-tetrahydro-4H-thiazolo[5.4-b]azepine 2-phenyl-5.6,7.8- Tetrahydro 4H-thiazolo[5.4-b]azevin (2.65 g) and triethylamine (2.21) were added to 30H tetrahydrofuran, and 4.65 d of stearoyl chloride was added dropwise with stirring while cooling with water. After completion of the dropwise addition, at room temperature. After 1.5 hours, the solvent was distilled off under reduced pressure.The residue was extracted with chloroform, and the extracted layer was washed with water, dried, and the shielding medium was distilled off.The residue was purified by column chromatography on linica gel to obtain the title compound (4). .31g, 76
%) was obtained. Melting point 38-40°IR(KBr)cm-': 2900, 2850
, 1670, 1640, 1450. 1410 NMR (CDC7!3) δ 0.87 (3H, t, J=
6Hz), 1.24 (30H.br.s), 1.5
2-2.10 (4H, s). 2.41 (2H, t, J
-5Hz), 2. 97 (2H, t, J= 5
Hz), 3. 61-3. 92 (2H, m) completed. 32-7.53 (3}!, m), 7.81-8
．． 03 (2H, m) Elemental analysis value: C3, H,, N2
Calculated value as 0S: C, 74.95; H, 9.7
4; N, 5.64. Actual value C, 74.64: H,
9.67; N, 5.77. Example 41 4-methanesulfonyl-2-(4-pyridyl)5,6,
7.8-Tetrahydro-4H~thiazolo[5,4-b]
azepine isonicotinic acid (10 g) in dimethylformamide (3
0 0 was 111%, carbonylimitazole (15.8 g) was gradually added to liquid i, and after stirring in a room for 30 minutes,
10.4 g of 3-amino-ε monolactam was added. After stirring at room temperature for 3 hours, the solvent was distilled off under reduced pressure. 200 d of pyridine and 12.4 g of phosphorus pentasulfide were added to the residue, and the mixture was heated under reflux for 1.5 hours. The solvent was distilled off under cooled pressure, and the residue was extracted with chloroform. The extracted layer was washed with aqueous sodium bicarbonate and water, dried, and the solvent was distilled off under reduced pressure.1 4.3
g of powder was obtained. 30-tetrahydrofuran and 2.28 M triethylamine were added to 2.5 g of this powder, and 1.08 d of methanesulfonyl chloride was added dropwise with stirring while cooling with water. After stirring at room temperature for 1 hour, the solvent was distilled off and the mixture was extracted with chloroform. The extracted layer was washed and dried, and the solvent was distilled off under reduced pressure. The residue was purified with a silica gel column and then recrystallized from methylene chloride isobrobyl ether to obtain 105 g (24%) of the title compound.

Melting point 193-194° IR(KBr)cm-': 1595, 1530
, 1430, 1370, 1340, 1150. NMR (CDC(.) δ・t. 56-2. 16(4
Fl, resistance, 3. QQ3.20 (2H, m), 3.04
(3H, s), 3.79 (2H, t, J=5Hz)7
．． 66-7.80 (2H, m), 8.61-8.78
(2Lm) Elemental analysis value: C13}1.5N302S
．． Calculated value: C, 50.46; H, 4.89
; N, 13.58 actual value・C, 50.33; H,
4.91; N, 13.61 Example 42 4-(5-methyl-4-isoxazolyl)carbonyl-2-methyl-5.6,7.8-tetrahuman-4H-
Thiazolo[5.4-b]acepine 2.55 g of 3-acetylamino-ε-cabrolactam and phosphorus pentasulfide (6.08
) was added to pyridine No. 41 and stirred in an oil bath at 80°C for 20 hours. After cooling, chloroform was added to the reaction mixture, and the mixture was washed with aqueous sodium bicarbonate and water. After drying, the solvent was distilled off under reduced pressure, yielding 259 g of oily fruit. This oil was dissolved in 40 d of pyridine, and 4 g of (5-methyl 4-isoxazolyl) carbonyl chloride was added dropwise under water cooling. After completion of the passage, the mixture was stirred at room temperature overnight and extracted with chloronarum. The extracted layer was washed with water, dried, and the solvent was distilled off under reduced pressure. The residue was purified by Rikakel column chromatography, followed by recrystallization from hexane to yield 0.9 g (19%) of the title compound.

Melting point] 1 7.0-] 1 85° I R (Nujol) cm': 1650, 160
5, 1560. 14501400 1240
1180 NMR (CDCI6 1.5-2.2 (4H, m),
2.9-3.2 (211, m), 3. 7-4.
0(2H, m), 2. 60 (6H, s), 7
．． 60 (IH, S) Elemental analysis value: C,, H, Calculated value as 5N302S: C, 56.30; H, 5.45; N, 15,
15 Actual value: C, 56.33: H, 5J3; N
, 14.94. Example 43 4-(4-fluorobenzoyl)-2-methyl-5.6,
7.8-Tetrahydro-4H-thiazolo[5.4b]azepine Similarly to Example 42, the title compound was obtained from 3-acetylamino epsilon-lactam, phosphorus pentasulfide and 4-chlorobenzoyl chloride ( yield 37%). Melting point 9 3.
5 0-9 5.0 0° (recrystallized from hexane), IR (Nujol) cm-': 1640, 160
0, 1440. 14051315, 1295,
1225. 1180,845,760 NMR (CD Cf23) δ: 1. 6-2.
2 (411, m), 2. 48 (311, s),
2.90-3.17 (2H.m), 3.77-4.
00 (2H.m), 6.837. 53 (4H, m
). Elemental analysis value: C,, calculated value as H15N20SF: C, 62.05; H, 5.21. N, 9.6
5 Actual value: C, 62.24; H, 5.28: N
, 9.60. Example 44 4-(α-Thenoyl)-2-methyl-5.6,7.8-
Tetrahydro-4H-thiazolo[5.1-b]acepine Similarly to Example 42, the title compound was obtained from 3-acetylamino ε-cabrolactam, phosphorus pentasulfide and α-thenoyl monochloride (yield 45%). ).

Melting point 108. OllO. O' (recrystallized from hexane) I R (Nujol) am-': 1630, 144
0, 1420, 1302, 1290. 1180,
735. NMR (CDCj3) δ: 1. 6-2. 3 (4H
, m), 2. 57 (3H, s) 2.88-3.
15 (2H, m) 3.73-4.03 (2H, m)
．． 6,857. 50 (3H, m). Elemental analysis value: Calculated value as C + 3Hl4N to s t C, 56.09; H, 5.07; N, 1
0.06 Actual value: C, 56.12; }{, 5.0
4; N, 10.02. Example 45 4-Nicotinoyl-2-methyl-5.6,7.8tetrahydro-4H-thiazoloE5,4-b]acepine In the same manner as in Example 42, 3-acetylamide/ε-1-cubic lactam, The title compound was obtained from phosphorus sulfide and nicotinic acid chloride (yield 34%). Melting point 107.0-
109.0' (recrystallized from hexane). IR(Nujol)am-': 1650. 158
5, 1550, 1465, 1420 1310,
1290. 1180,740 N M R (C D C f23) δ: l. 8-
2. 3 (4H, m), 2. 45 (3H, s)
2.92-3.20 (28, m). 3.77-4.0
3 (2H, m), 7.138. 6 (4H, m) Elemental analysis value: C + 4H + sN 30 Calculated value as S: C, 61.52; H, 5.53; N,
15J7, actual value: C, 61.84; H, 5.5
5;N. 15.20 Example 46 2-(3-methoxystyryl)-5.6,7.8tetrahydro4H-thiazoloC5,4-b]acevin hydrochloride In the same manner as in Example 1, 3-(3-methoxystyryl)-5.6,7.8 /nnnamoyl)amino-ε monocabulactam and phosphorus pentasulfide were reacted, and the purified product was neutralized with hydrogen chloride to obtain the title compound (yield 3o, 3%). Melting point: 177,178° (chloroform-ethanol recrystallization). I R (K B r) cm-': 3366, 3
216, 2930, 1604, 1525.148
9.1269. NMR (d8-DMSO) δ: l. 63-1.
74 (4H, m), 2. 80-2. 86 (2H,
m), 3. 01-3. 07 (2H, rn),
3. 80 (3H, s), 6. 94 (IH,
dd, J = 3Hz. 7Hz), 7. 18-
7. 20 (2B, m), 7. 32(IN, d
, J = 8Hz), 7. 38 (2H, s).
Elemental analysis value: CI. H. ．． N, OSC (calculated value as l: C, 59.52: H, 5.93; N, 8
．． 5g. Actual value: C, 59.19; H, 5.85;
N, 8.69. Example 47 2-(3.5-dimethoxystyryl)-5.6,7.8
-Tetrahydro4H-thiazolo[5.4-b]azebin By the same method as in Example 1, the title compound was obtained from 3-(3.5-methoxycinnamoyl)amino-ε-caprolactam and phosphorus pentasulfide. Yield 2i. 4%). Melting point 104-105° (recrystallized from ether). I R (K B r) am””: 1594, 1
546. 1431, 1419, 1355, 120
7, 1156. NMR (CDCl23) δ: 1.62-1.90 (
4H, m), 2.90 (2}1, t, J = 6Hz
), 3. 12 (2H, t, J=5Hz),
3. 81 (6H, s), 3. 93 (IH, br
), 6. 40 (IH, t, J= 2Hz),
6. 62 (2H, d, J= 2Hz), 6.
92 (IH, d, J= 16Hz), 7. 10
(IH. d, J= 16Hz). Elemental analysis value; Calculated value as C 17H , oN so ts: C, 64.53: H, 6.37; N,
8.85. Actual value: C, 64.59; H, 6.5
2; N, 8.80. Example 48 2-(2.3-Nmet Beef/Stiwal')-5.6
．． 78-Tetrahydro l-48-thiazoc7[5.1-b
] The title compound was obtained from 3-(2,3-dimethoxycinnamoyl)amino-ε-monolactam and phosphorus pentasulfide by pouring in the same manner as in Example 1 of Azepine (yield: 35.0%). Melting point 125-126° (recrystallized from cyclohexane), I R (K B r) cm-': 3214, 1
527, 1476, 4447, 1422, 1270
, 1072. NMR (CDCt2.) δ: 1. 501. 89
(4H, m), 2. 90C2H. t, J-
6Hz), 3. 12 (2H, t, J = 5H
z), 3. 85 (3H.s), 3. 88 (3
H, s), 6. 84 (IH, dd, J=
2Hz, 8Hz>, 7. 05(IH, t, J
= 8Hz), 7. 15 (IH. d, J =
16Hz), 7. 16(II, dd, J= 2
Hz, 8Hz), 7. 31 (IH, d. J=
16Hz). Elemental analysis values: C, 7H, . N,
Calculated value as O, S: C, 64.53. H, 6
．． 37; N, 8.85. Actual value: C, 64.44
; H, 6JO' N, 8.91, Example 49 2-(2.5-dimethobovcystyryl)-5.6, 7.8
-Tetrahydride-4H-thiazolo[5.4-b]acepine The title compound was obtained from 3-(2,5-dimethoxycinnamoyl)ami7-ε-cabrolactam and phosphorus pentasulfide in the same manner as in Example 1. (yield 32.3%). Melting point 155-156° (recrystallized from cyclohexane), I R (K B r) cm-': 1527, 1
498, 1436, 1362, 1226, 121
3. N M R (C D C (23) δ: 1.5
0-1. 18C4H, m), 2. 74(2}!
, t, J = 6Hz), 2. 92-3. (1
2 (2H, m), 3. 75 (3H, s), 3
．． 80 (3■, s). 6. 83 (IH, dd
, J-3}iz, 9Hz), 6. 96 (IN
, d, J = 9Hz). 7. 18-7. 2
1 (3H, m) Elemental analysis value: C,,H,. N
,O. Calculated value as S: C, 64.53; H,
6.37; N, 8.85 Actual value: C, 64.39
; H,6,31: N,8.71 Example 50 2-(3.4-dimethoxyphenyl)-5.6,7.8
~Tetrahydro-4H-thiazolo[5.4-b]azepine hydrochloride By the same method as in Example 1, 3-(3,4-dimethoxybenzoyl)amino-ε monocubic lactam and phosphorus pentasulfide were reacted and purified. The post-product was neutralized with hydrogen chloride to obtain the title compound (yield 45.4%). Melting point 186-187° (recrystallized from methanol-ether) I R (K B r) cm': 1609,
1535, 1509, 1342. 126g, 1
152. NMR (d.-DMSO) δ: 1. 56-1.
82 (4H, m), 2. 88-2. 94 (2H,
m), 3. 02-3. 08 (2H, m),
3. 82 (3H, s), 3. 85 (3H, s)
, 7. 05 (IH, d, J = 9Hz),
7. 35 (IH. dd, J2Hz, 9Hz),
7. 58 (IH, d, J= 2Hz). Elemental analysis value 2C +sH 1sN to tc (l・0.
Calculated values as 5H, O: C, 53, 64; H, 6.00; N,
8.34. Actual value: C, 53J9; H, 5.86
; N, 8.05 Example 51 2-(4-methoxy3-methylstyryl)-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4b]azepine 3-(4-methquine-3
The title compound was obtained from -methylcinnamoyl)amino-ε-monocablactam and phosphorus pentasulfide (yield 33.6%).
. Melting point 139-140° (recrystallized from cyclohexane)
．． I R (K B r) cm': 2922, 1
542, 1506, 1365, 1255, 112
9. NMR (CDCQ3) δ: l. 59-1. 88
(4H, m), 2. 22 (3H, s), 2.
89 (28, t, J= 6Hz), 3. 11(
2H, t, J=5Hz), 3. 84 (3H,
s), 6. 80 (LH, d, J = 9Hz)
, fi. 96 (2H, s), 7. 26-7.
30 (2H, m). Elemental analysis values: C,,H,. N. Calculated value as OS: C
, 67.97; H, 6.71; N, 9.32.
Actual value: C, 6g. 19; H, 6.80: N
,9J9. Example 52 2-[4-methoxy3-(2-methylthioethoxy)
3-[4-methoxy3-(2-methylthioethoxy)cinnamoyl]amino-ε The title compound was obtained from one cabbage lactam and phosphorus pentasulfide (yield 15.0%). Melting point 117-118° (recrystallized from cyclohexane). I
R (K B r) cm': 1553, 15
14, 1442. 135g, 1263,1141
．． NMR (CD Cl2 3) δ 2 1.
48-1. 97 (4H, m), 2. 20 (3H
s), 2. 81-2. 95 (2H, m), 2
．． 90 (2H, t, J=7Hz), 3. 0
43. 17 (2H, m). 3. 85 (3H.
s), 4. 20 (2H, t, J=7Hz),
6. 81 (IH, d, J = 9Hz), 6,
92 (2H, s), 6. 97-7. 06 (2H
, m) Elemental analysis value: C. ．． H. Calculated value as N, ○tSt: C, 60.61; H, 6.42; N
，? ．． 44. Actual value: C, 60.62; H, 6.
47; N, 7.40, Example 53 2-(3.4.5-}rimethoxystyryl)-5,6,
7.8-Tetrahydro 4H-thiazolo[5,4b]azepine hydrochloride In the same manner as in Example 1, 3-(31415-trimethoxycinnamoyl)amino-ε monolactam and phosphorus pentasulfide were reacted and purified. The post-product was neutralized with hydrogen chloride to obtain the title compound (yield 22.8%).

Melting point 204-205° (recrystallized from methanol-ether). I R (K B r)cn+-': 2910,
1572, 1500, 1432, 1410, 12
3i! l, +120. NMR (d.-DMSO) δ: l, 55-1.
80 (4H, m), 2. 77-2. 85 (2H,
m), 3. 02-3. 09 (2H, m),
3. 69 (3H, s), 3. 82 (6H, s)
, 6, 95 (2■, s). 7. 28 (2H,
s) Elemental analysis value: C,. Calculated value as H, 3N, 033C9: C, 56.46; H, 6.05; N
, 7J2. Actual value: C, 56.14; H, 6.0
1; N, 7.28. Example 54 2-(3-ethoxycarbonyloquine-4-methoxystyryl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b coazebin 3-( The title compound was obtained from 3-ethquincarbonyloxy-4-methoxycinnamoyl)amino-epsilon-caprolactam and phosphorus pentasulfide (yield 65.4%).

Melting point 132-133° (recrystallized from isopropyl ether). r R (K B r) cm-': 1761, 1
514, 1439, 1368, 1276, 113
7, 1059. NMR (CDC I23)δ: 1.3g
(3H, t, J=7Hz), 1.501. 95 (4H
, m). 2. H-2. 92 (2H, m),
3. 02-3. 13 (2H, m), 3. 86(
3B, s), 4. 30 (2H. q. J =
7Hz), 6. 1110-7. 00. (IH,m
), 6. 94 (2H, s), 7. 25-7.
37 (2H, m). Elemental analysis value: C. 9H,
,N. 0. Calculated value as S: C, 60.94;
H, 5.92; N, 7.4111. Actual value C, 6
0.86; H, 5133; N, 7, 52 Example 55 2(2.4-7methoxystyryl)-5.6,7.8-
Tetrahydro 4H-thiazolo[5.4-b]azepine hydrochloride In the same manner as in Example 1, 3-(2.4-methquinnannamoyl)amine-ε-capsulactam and phosphorus pentasulfide were reacted and purified. The post-product was neutralized with hydrogen chloride to obtain the title compound (8.5% yield). Melting point 165-167° (recrystallized from methanol-ether). I R (K B r)c
m': 1603, 1542, 1505, 1
433. 12g9, 1265, 1209. 115
8 NMR <c D cc3) δ: 1.5g-1.8
9 (4B, m), 2. 862. 91 (2H,
m), 3. 08-3. 13 (2H, m), 3
．． 83 (3H, s), 3. 86 (3tl, s
), 6. 47(Ill, dd, J = 2Hz
, 8Hz), 6. 52 (IH, d, J2Hz
), 7. 09 (IH, d, J= 16Hz).
7. 25 (18, d, J= 16Hz), 7
．． 42 (IH, d, J = 8Hz). Elemental analysis value: C17H, IN202SCQ・t. Calculated value as 5H20: C, 53.75; H, 6.37; N
, 7.37 Actual value: C, 54.02. H. 6.1
0; N, 7.44. Example 56 1-(4-ethoxylponyloxyphenyl)5,6
,7.8-tetrahydro-4H-thiazolo[54-b]
The title compound was obtained from 3-(4-ethoxy/carponyloxybenzoyl)amino-e-capsulactam and phosphorus pentasulfide in the same manner as in Azepine Example 1 (yield 21.3%).
.

Melting point 93-94° (recrystallized from ether-hexane) T R (K B r) cm-': 1753, 1
50g, 1370, 1302, 1258, 120
7. NMR (CDCh) δ: 1.36 (3H, t, J=
7Hz), 1.50-1. 95 (48, m), 2
．． 85-2. 97 (2H, m), 3. 02-
3. 12 (2H, m)3. 85 (IH, br)
, 4. 30 (2}1, q, J = 7Hz).
7. 16 (2H, d, J-9Hz), 7.
75 (2H, d, J = 9Hz) elemental analysis value・C
、． H. Calculated value as N 20 3S: C, 6
0.36; H, 5.70, N, 8.80; S
10.07 Actual value: C, 60 Jl; H, 5.60; N,
8.74;S 10.12. Example 57 2-(3-promo 4-methkinstyryl)-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4b]azepine By the same method as in Example 1, 3-(3-bromo4-
The title compound was obtained from metquincinnamoyl)amino-ε-caprolactam and phosphorus pentasulfide (yield 25.0%)
. Melting point: 158-159° (recrystallized from ethyl acetate). I R (K B r) cm': 1546, 1
499, 1440, 1352, 1291.125
8 NMR (CDC(!+)δ: 1.61-1.87(
4H, m), 2. 89 (2H, t, J= 6H
z), 3. 09-3. 14 (2H, m), 3
．． 91 (3H, s), 6. 88 (IH, d,
J=9tlz), 6. 93-6. 94 (2t
{, m), 7. 37 (IH, dd, J-2H
z, 9Hz), 7. 66 (IH, d, J =
2Hz). Elemental analysis value: C, 6H, 7N 20
Calculated value as SBr: C. 52.61; H, 4.
69; N, 7.67. S, 8. 7g. Actual value: C, 52.37; H, 4.64; N
, 7.60; S 8.92. Example 58? -(3.5-di-tert-butyl-4-hydroxyphenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]acepine hydrochloride In the same manner as in Example 1, 3 -(3.5-Di-tertbutyl-4-hydroxybenzoyl)amino epsilon-cabulactam was reacted with phosphorus pentasulfide. After purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield: 11.8 %). Melting point 19=l196°(
Recrystallized from ethanol-ether) IR (KBr)am-': 34g6, 3
220, 2924. 1608. 1394+307
1226 1119 NMR (CDCQ3) δ: 1.49 (18H, s)
, 1.61-1.87 (4H, m), 3. 11-
3. 16(2}1, m), 3. 24-3. 3
0(2H, m), 5. 82 (IH s), 7.
83 (2H, s). Elemental analysis value: C21H3
, N t○SCQ: C, 63.85.
H. 7.91. N,? ．． 09. S, 8.12;
C color 8. 98. Actual value C, 64.03; H
, 7.99. N, 6.90S, 8.02; 'C
(,8.86.Example 59 2-(2.4-7methoxyphenyl)-5.6.78-
Tetrahydro-4H-thiazolo[5.4-b]azepine hydrochloride In the same manner as in Example 1, 3-(2,4-dimethoxy/benzoyl)amino-ε-cabrolactam and phosphorus pentasulfide are reacted and produced after purification. The product was neutralized with hydrogen chloride to obtain the title compound (yield 56.2%). Melting point 214-215° (recrystallized from ethanol-ether), I R (K B r')
cm': 3198, 1610, 1572,
1527. 1321, 1300. 12]2. NMR (d.-DMSO) δ: 1.55-1.81
(4H, m)2. 90-2. 97 (2H, m),
3. 02-3. 10 (2H, m), 3. 8
6 (3H, s), 3. 99 (3H, s), 6.
71-6. 79 (2H, m), 8. 31 (I
H, d, J = 911z) Elemental analysis value: C 15H IEN t○, calculated value as SCQ: C, 55.12; H, 5.86;
N, 8.57; S, 9.81; Cf2, 10.
85. Actual value: C, 54.97; H, 5.84;
N, 8.64; S, 9.79; Cff, 1
0.80. Example 60 1-(3.4-dimethylstyryl)-5.6,7.8tetrahydro-4H-thiazolo[5.4-b]acepine By a method similar to Example 1, 1(3.4- The title compound was obtained from dimethylnonnamoyl)amino-ε-caprolactam and phosphorous pentasulfide (yield 504%). melting point 16
5-166° (recrystallized from ethyl acetate). I R (K B r) cm': 3258, 2
944, 2920, 1544. 14311,35
5. N M R (C, D C +23) δ: 1.
52-1. 96 (4H, m), 2. 26 (6H
, s), 2. 80-2. 92 (2H, m),
3. 03-3. 14 (2H, m), 3. 86
(IHbr), 7. 00 (28, s), 7.
11-7. 25 (3H, m). Elemental analysis value C,
,H,. Calculated value as N and S: C, 71.79.
H, 7.09; N, 9.85S, 11. 2
7. Actual value: C, 71.92; H, 7.03; N
, 9.83;S, 11. 43 Example 61 2-(2-methoxy3-methylstyryl)-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4b]azepine 3-(2-methoxy-3
The title compound was obtained from -methylcinnamoyl)amino-ε-monocablactam and phosphorus pentasulfide (yield 45.3%)
. Melting point 114-115° (recrystallized from Koichitel). r R (K B r) cm-': 3216, 2
920. 152g, 1436. 136g, 135
3. 1005 NMR (d.-DMSO) δ: I. 62-1.
89 (4H, m), 2. 31 (3H, s), 2
．． 90 (2H, t, J = 6Hz), 3.
12 (2H.t, J-5Hz). 3. 75 (3
H, s), 7. 02 (18, t, J= 8H
z), 7. 12 (IHdd J = 2Hz, 8
Hz), 7. 14 (IH, d, J= 16Hz
), 7. 28 (IH, d, J = 16Hz),
7. 39 (IH, dd, J = 2Hz, 8
t(z). Elemental analysis value: C l? H 20N 20S
Calculated values as: C, 67.97; H, 6.71;
N, 9.32; S, 10. 67. Actual value: C, 67.91; H, 6.69; N
, 9J4;S, 10. 85. Example 62 2-(3-methoxyphenyl)-5.6,7.8tetrahydro-4H-thiazolo[5.4-b]azepine 3-(3-methoxybenzoyl) ) The title compound was obtained from amino-ε-monocuboid lactam and phosphorus pentasulfide (yield 40.0%). Melting point 82-8
3° (recrystallized from cyclohexane). I R (K B r)cn+-': 3206,
1597, 1495, 1370, 1272.78
5 NMR (C D CQ3) δ: 1. 61-1.
90 (4H, m), 2, 95 (2H, t, J
= 6Hz), 3. 12 (2H, t, J =
5Hz), 3. 86 (3H, s), 6. 84
-6. 90 (IH, m), 7. 22-7. 3
6 (3H, m) elemental analysis value C,. }I,,N
, OS Calculated value: C, 64.59; H, 6
．． 19; N, 10, 76; S, 12. 32. Actual value: C, 64.52; H, 6, 03; N
, 10, 49;S, 12. 44. Example 63 2-(α-methylstyryl)-5.6.7.8-tetrahydro-4H-thiazolo[5.4-b]azebin 3-(α-methylstyryl)-5.6.7.8-tetrahydro-4H-thiazolo[5.4-b]azebin The title compound was obtained from the (moyl)amino-ε-monolactam and phosphorus pentasulfide (yield 16, 6%). Melting point 122-
123° (recrystallized from isopropyl ether)! R(KBr)cm-': 3226, 2
922, 1552, 1512, 1432, 136
2, H55, 696 NMR (CD CC3) δ: 1. 61-1.
89 (48, m), 2. 32 (3Hs), 2
．． 92 (2H, t, J = 6Hz), 3.
11 (2H, t, J=5Hz), 3. 91(
11 br. s), 7. 13-7. 39 (6H
．． m). Elemental analysis value: C,. H. Calculated value as N, S: C,? 1.07; H, 6.71.
N, 10.36;s, 11. 86. Actual value: C, 71.01; H, 6.55; N
, 10.28;S, 11. 6:{, Example 64 2-(4-}lifluoromethylphenyl)-5.6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azepine The title compound was obtained from 3-(4-trifluoromethylbenzoyl)amino-ε-monocablactam and phosphorus pentasulfide in the same manner as in Example 1 ( yield 50.4%). Melting point 158,159° (recrystallized from cyclohexane). T R (K B r) am-': 1518. 1
330, 1159, 1121, 1069,837
．． NMR (CDC(3)δ: 1.65-1.91(4
H. m), 2.942. 99 (2H, m), 3.
14 (2H, t, J=5Hz), 4. 00
(IH. br. s) 7, 61 (2H, d, J-
8Hz), 7. 1116 (2H, d, J=
8Hz) Elemental analysis value: C 14H 13N ts F
Calculated value as 3 C, 56, aa; H, 4J9;
N, 9J9; S 10.75・F, 19.
10. Actual value: C, 56.39; H, 4J3;
N, 9.40; S, 10.78. F, 1g, 9
2. Example 65 2-(3.4-methylenedioxyphenyl)-5.6,
7.8-tetrahydride-4H-thiazolo[5,4b]azepine hydrochloride In the same manner as in Example 1, 3-(3,4-methylenedioxybenzoyl)amino-ε-cabrolactam and phosphorus pentasulfide were reacted, After purification, the raw botanical was neutralized with hydrogen chloride to obtain the title compound (yield 27.2%). Melting point 190192° (recrystallized from methanol-ether) 9 I R (K B r) cm': 3196, 1
619, 1602, 1506, 1348.126
6 NMR (CDC4) 3) δ: 1, 68-1. 90(
4H, m), 3. 173. 28 (4H, m)
．． 6. 04 (2H, s), 6. 85 (IH,
d, J=8Hz, )7. 56 (IH, s)
, 7. 65 (LH, d, J = 8Hz) Elemental analysis value CI4H 15N t0 2S C Calculated value as Q: C, 54.10; H, 4.1116;
N, 9.0L; S, +0.32; (J!, 11.4
1. Actual value: C, 53.72; H, 4.99;
N, 8.85; S, 10. 26; Cff
, 11. 13. Example 66 2-(p-}lyl)-5.6,7.8-tetrahydro4
The title compound was obtained from 3-(p-toluoyl)amino-epsilon monolactam and phosphorus pentasulfide by pouring in the same manner as in Example 1 of H-thiazolo[5.4-b]azepine (yield: 43. 4%). Melting point 128-129° (recrystallized from cyclohexan). I R (K B r) cm-
': 3236, 3018, 2918, 151
6, 1460,! 372,816. NMR (CDCl23) δ: 1. 61-1. 8
9 (4H, m), 2. 35 (3Hs), 2.
91-2. 97 (28, Wl), 3. 11(2
H, t, J=5Hz), 7. 11 (2H.
d, J=8Hz), 7. 65 (2H, d,
J = 8Hz). Elemental analysis value: C,,H,,N
Calculated value as 2S: C, 6181; H, 6.6
0: N, 11.46; S, 13. 12. Actual value: C, 68.57; H, 6.60: N
, 11.62;S, 13. 28. Example 67 2[4(tert-butoxycarponylaminomethyl)phenyl]-5.6,7.8-tetrahydro4
H-thiazolo[5.4-b Coazebin By a method similar to Example 1, the title compound was obtained from 3[4(tertbutquinecarbonylaminomethyl)penzoyl]ami/1epsilon-cabrolactam and phosphorous pentasulfide. (yield 1
9.6%). Melting point 170171° (recrystallized from ethyl acetate), I R (K B r) am ': 3312, 1
673, 1524. 136g, 1269,116
7. N M R (C D C f23) δ: 1. 4
6 (9H, s), 1. 64-1. 90 (4Hm
), 2. 94 (2H, t, J=6Hz),
3. 11 (2H, t, J = 5Hz), 4.
31 (2H, d, J= 6Hz), 7. 27
(2H, d, J = 8Hz), 7. 72 (2
+{, d, J=8Hz') Elemental analysis value・C I9H 25N 30, Calculated value as S: C, 63.48; H, 7.01; N, 1
1.69; S, 8.92. Actual value: C, 63.47; H, 7.07; N
, 11.7g. S, 8.86 Example 68 2-(2,3.4-trimethoxyphenyl)-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4b]azebin The title compound was prepared from 3-(2.3.4trimethoxybenzoyl)amino-ε monolactam and phosphorus pentasulfide by a method similar to Example 1. was obtained (yield 18.9%). Melting point 133-134° (recrystallized from ethanol), I R (K B r) am-': 2934, 1
553. 149g, 1437, 1290,109
2. NMR (CDCff3) δ: 1. 60-1. 9
0 (4H, m), 2. 95 (2H, t, J =
6Hz), 3. 11 (2H, t, J= 5H
z), 3. 89 (6H, s), 3. 96(3)
{, s), 6. 74 (IH, d, J= 9H
z), 7.89 (IH, d, J = 9Hz). Elemental analysis value: Calculated value as C16H toN203S: C, 59.98; H, 6.29; N
, 8.74; 3 10.01 Actual value: C, 59.94; H, 6. :{6;
N. 8, 63; S, 9.95. Example 69 2-(3-trifluoromethylstyryl)-5.6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azepine By the same method as in Example 1, the title compound was obtained from 3-(3-trifluoromethylcinnamoyl)amino-ε-monolactam and phosphorus pentasulfide. (yield 51.0%).

Melting point l51-152° (recrystallized from cyclohexane). I R (K B r) cm””’: 3260,
1546. 1517, 1334, 1160.1+
24. NMR (CDCQ3) δ: 1. 63-1. 89
(4H, m), 2. 882. 94 (2H, m
), 3. 13 (2H, t, J = 5Hz).
4. 02 (IH, br. s), 7. 01(I
H, d, J= 16Hz), 7. 1'5 (IH
, d, J = 16Hz), 7. 437. 6
8 (4H, m) Elemental analysis values: C, 6H, 5N. Calculated value as SF 3: C, 59.25; H, 4.66; N
, 8.64; S, 9.89; F, 17.57. Actual value: C, 59.20; H, 4.63; N,
8.53;S, 9.67. F, 17.39. Example 70 2[2(tert-butoxycarbonylamino)ethyl]-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azebin 3-(N -te
The title compound was obtained from rt-butoxycarbonyl-[beta]-alanyl)amino[epsilon]-caprolactam and phosphorus pentasulfide (yield 27.2%). Melting point 151-153° (recrystallized from ethyl acetate) 9 r R (K B r) cm-': 3340, 2
924, 1688, 1547, 1282, 126
2, 1161. NMR (d8-DMSO) δ: 1. 44 (9H,
s), 1. 561. 87 (4H, m). 2
．． 81-2. 87 (2H, m). 2. 94(
2H, t, J-6Hz), 3. 05 (2H
, t, J = 5Hz), 3. 41-3. 5
2 (2H.m). Elemental analysis value: CI4H tsN
Calculated value as 30 tS: C, 56.54. H
, 7, 79; N, 14.13; S, 10. 7
8 Actual measurement value: C, 56.51; H, 7.91; N
, 14.17;S, 10. 79. Example 71 2-(4-methoxycarbonylphenyl)-5,6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b1 azebin] The title compound was obtained from 3-(4-methoxy/carbonylhenzoyl)amino-ε-monolactam and phosphorus pentasulfide by a method similar to Example 1. (Yield 56.6%). Melting point 168-170' (recrystallized from methanol) I R (K B r) cm-': 1730, 1
510, 1441, 1274, 1175.111
4 NMR (CDCI23) δ: 1.45-1.98 (
4H, m), 2.903. 02 (2H, m), 3
．． 07-3. 18 (2H, m), 3. 92(
3H, s), 7. 78 (2H, d, J= 9
Hz), 8. 01 (2H, d, J= 9Hz)
．． Elemental analysis values: C, 5H, . Calculated values for N, O, S: C, 62.48; H. 5.59;
N, 9.71; S, 11.12 Actual value: C, 62.39; H, 5.59; N
, 9.87;S, 11. 11 Example 72 2-(4-ethquinylsulfonylstyryl)-5.6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azepine The title compound was obtained from 3-(4-ethoxycarponylcinnamoyl)amino-ε-monocaprolactam and phosphorus pentasulfide in the same manner as in Example 1. rate 8.7%). Melting point 149-150' (recrystallized from ethyl acetate) I R (K B r) am': 1715, 1
522, 1356, 1275, 1252, ・11
04. NMR (CD CQ3)δ: lJ9(3H,t
, J=7Hz). 1.601. 86 (4H.m),
2. 88-2. 94 (2H, m), 3. 1
1-3. 15 (2H, m), 4. 38 (2H,
q, J=7Hz), 7. Of(IH, d,
J = 16}1z), 7. 18 (IH, d,
J=16Hz), 7. 50 (2H, d, J=
8Hz). 8. 01 (2H, d, J8Hz)
．． Elemental analysis value: Calculated value as C 18H 20N 20 2S: 'C, 65, 83; H, 6.14.
N, 8.53. S 9.76, actual value: C, 65.87. H, 6.10. N
, 8.62; S, 9.62. Example 73 2-[1-(tert-butquine carbonylamine/
) Ethyl]-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azepine In a similar manner to Example I8, N-tert-butoxycarbonylalanine, 3-amino-epsilon The title compound was obtained from lactam and phosphorus pentasulfide (yield 8
3%). Melting point 180-182° (recrystallized from ethyl acetate). T R (K B r) cm': 3244, 1
694, 1513, 1368, 1248, 117
1. NMR (CDCC3) δ: 1.45 (9H, s),
1.52 (3H, d, J-7Hz). 1. 56-1
．． 86 (4H, m), 2. 84 (2H, t,
J = 6Hz), 3. 05 (2H, m), 4
．． 78-4. 90 (IH, m). Elemental analysis value:
C,. Calculated value as H 23N,0 2S・C,5
6.54; H, 7.79; N, 14.13; S
, 10. 78 Actual value: C, 56.70; H,? ．． 81; N
, 14.11:S, 10. 7g. Example 74 2-(4-pyrinyl)-5.6,7.8-tetrahuman-4H-thiazolo[5.4-. b] Acevin Example 18
In the same manner as above, the title compound was obtained from isonicotinic acid, 3-amino-[epsilon]-monocuboid lactam, and phosphorus pentasulfide (yield: 42.0%). Melting point 169 - t70
° (recrystallized from ncrohexane) I R (K B r
) am"-': 1597. 1528, 1491
11, 1439, 1372, 1360. NMR (CDCi23) δ: 1. 60-1. 9
8 (4H, m), 2. 90=3.00(2H, m
), 3.06-3.18 (2H.m), 4.1 1 (I
H, br. s), 7. 60 (2H. d, J =
6Hz). 8. 56 (2H, d, J= 6Hz
). Elemental analysis value: Calculated value as C, = H, 3N, S: C, 62, 31; H, 5.66; N, 1
8.17;S, 13. l! 6. Actual value: C, 62.45; H, 5.64; N
, 18.07;S, 13. 82. Example 75 2-(3-hydroxy-4-methoxystyryl)5,6
,7.8-tetrahydro-4H~thiazolo15.4-b
]Azepine hydrochloride 1-(3-ethoxyluponyloxy-4-methkinstyryl) 1. 5,6,7.8-tetrahydro 4H~thiazolo[5.4-b]azevin (13.2 g) at 600
In addition to the 1N ammonia methanol elution in step d, 3
Stir for hours. The solvent was distilled off under reduced pressure, and the residue was purified by Norikakel column chromatography.
Hydrogyf C-4-Me1-Kysistyril-5.6,7.
8.74 g (819%) of 8-tetrahydro4H-thiazolo[5.4-b]azevin was obtained. Part 1.
50 g was converted into a hydrochloride salt and recrystallized from methanol-ether to obtain 0.49 g (29.0%) of the title compound.

Melting point 2] 0-211° I R (K B r) cm"-': 3216,
2530, 1601. 1504. 1279947 NMR (d6-DMSO) δ 1. 56-1. 7
9 (4H, m)2. 76-2. 87 (2H, m
), 3. 02-3. 10 (2H, m). 3.
81 (3H, s), 6. 944. 12 (4H,
m), 7. 31 (IH, d, J= 16Hz
). Elemental analysis value C. ．． H. N20, S Cff
Calculated values: C, 56.71; H, 5.65;
N, 8.27; S946 Actual value: C, 56.72; H, 5.63; N
, 8, 30:S. 9.60. Example 76 2-(4-hydrocyphenyl)-5.6,7.8tetrahydride-4 8-thiazolo[5.4-b]azepine.
The title compound was obtained from 2-(4-ethoxycarbonyloxyphenyl)-5.6,7.8tetrahydride-4H-thiazolo[5.4-b]azevin by pouring in the same manner as in Hydrochloride Example 75. (Yield 325%). Melting point 215-216°
(Recrystallized from ethanol-ether). I R (K B r) cm': 3378. 2
926, 1607, 1560, 1519, 127
9. 12311! ．． NMR (d.-DMSO) δ: 1.56-1.82
(48, m), 2. 83-2y93(2H, m),
3. 00-3. 1 1 (2H, m), 6.
89 (2H, d, J = 8Hz), 7. 73(
2H, d, J = 8Hz). Elemental analysis value: C,
Calculated value as 3H, 5N, OSCQ: C, 55.21
; H, 5.35; N, 9.91・S, 11
．． 34; C f2, 12. 54. Actual value:
C, 55.19. H, 5.41; N, 9.74
;S, 11. 10; C Q. ．． 12. 5
0 Example 77 2-(2-aminoethyl)-5.6.7.8-tetrahydro-4H-thiazolo[5.4-b]azepine dihydrochloride 2[2(tert-butoxycarponylamino)ethyl ]-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]Azepine (1.oog) in methanol solution (10d) was added with 3d of 4.75N hydrochloric acid methanol residue solution at room temperature for 5 hours. Stirred. The solvent was distilled off under reduced pressure, and the residue was washed with ether and recrystallized from methanol-ether to yield 0.64 g (70.0 g) of the title compound.
5%) I got a good fortune. Melting point 206208° I R (K B r) cm"" 2 3254
, 293B, 2844, 2796, 1616,
1531, 1500. NMR (de-DMSO)δ: 1.52-1
．． 85 (4H, m), 2.79-2. 84 (2H,
m), 2. 99-3. 05 (2H, m), 3
．． 19-3. 28 (411, m) Elemental analysis value C. H, 7N. Calculated value as S C4!2: C, 40.00. H, 6.34; N, 1
5.55; S, 11, 87. Actual value: C, 39.89; H, 6.29; N
, 15.24;S, 11. 87. Example 78 2-(4-aminomethylphenyl)-5.6.78-tetrahydro 4H-thiazolo[5.4-b]azepine.
2-[4-(tert
-butoxycarbonylaminomethyl)phenyl]-5.
6,7.8-Tetrahydro-4H-thiazolo[5.4-
b] The title compound was obtained from azepine (yield 65.4
%). Melting point 261-265° (recrystallized from methanol) I R (K B r) am-': 3224, 2
930, 1606, 1531, 1467, 137
2. 1125 NMR (d.-DMSO) δ: 1. 56-1.
86 (4H, m)2. 87-2. 93 (2H,
m), 3. 02-3. 08 (2H, m), 4
．． 01-4. 07 (2H, m), 7. 57(
2}1, d, J = 8Hz), 7. 85 (2
H, d, J= 81{z). Elemental analysis value: C,
．． H. Calculated value as N35 C&,: C,50.
60; H, 5.76; N, 12.65; S,
9, 65; C Q. 21. 34. Actual value:
C, 50.77; H, 5.73; N, 12.6
3. S, 9.56; Cl2, 21.26. Example 79 2-(4-methoxy3-pentyloxystyryl)-
5.6.7.8-Tetrahydro-4H-thiazolo [5.
4-b coazepine 2-(3-hydroxy-4-methoxystyryl)-5.
6,7.8-Tetrahydro-4H-thiazolo [5. 4
-b ] To a dimethylformamide solution 21 of azepine (1.00 g) were added amyl bromide (0.49 ml2) and potassium carbonate (0.46 g), and the mixture was stirred at 100° for 1 hour. After cooling, the reaction solution was filtered and the filter solution was dissolved in ether. This eluate was washed with water, dried, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography followed by recrystallization from isobrobyl ether to yield 0.19 g (15.4%) of the title compound. Melting point 124-
125°I R (K B r) cm-': 324
0, 2930, 1515, 1451. 1263
? 236.1022. NMR (CD Cff3)δ: 0. 94(3
H, t, J=7Hz), 1. 36-1. 9
3 (10B, m), 2. 89(.2H, t,
J = 5Hz), 3. 12 (2H, t), 3.
88 (3H, s), 4, 03 (2H, q, J
==7Hz), 6. 84 (LH, d, J-8
Hz), 6. 96-7. 04 (4H, i). Elemental analysis value: C■H,. Calculated value as N, O, S: C,
67,71, H, 1.58: N, 7.52 Actual value: C, 67.49; H, 7.43; N, 7
J9. Example 80 4-Methyl-2-phenyl-5.6,7.8-tetrahydride-4H-thiazolo[5.4-b]acevin hydrochloride 2-phenyl-5.6,7.8-tetrahydride -4H-
To 30 d of a dimethylformamide solution of thiazolo[5.4-b]azevin (0.83 g) was added methyl iodide (0.45
m) and potassium carbonate (0.75 g), and stirred for 90'
The mixture was stirred for 4.5 hours. After cooling, the reaction was heated overnight,
; Dissolved Toki into ether. After washing this toki with water and drying it,
It was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, neutralized with hydrogen chloride, and recrystallized from ethanol-ether to yield 0.53 g of the title compound (
52.4%) was obtained. Melting point 139-140' I R (K B r)cn+-': 321 g,
292g, 2564, 1591, 1524, 14
25, 1319. 767 NMR (d.-DMSO) δ: 1. 43-2.
00 (41, m). 2. 76-3. 16 (7H,
m), 7. 30-7.52 (3H.m), 7
．． 70-7. 93 (2H, II1). Elemental analysis value: C. ．． H,,N. Calculated value as S CQ: C, 59.88; H, 6.10; N, 9
．． 98:S, 11. 43. Actual value: C, 59.70; H, a. oo；N
, 9.86;S, 11. 51. Example 8l 4-Allyl-2-(4-methoxy3-methylstyryl-5.6.7.8-tetrahydro-4Hthiazolo[5
．． 4-b] Azevin hydrochloride 2-(4-methoxy-3-methylstyryl)-5 was prepared in the same manner as in Example 80.
．． 6,7.8~Tetrahydro-4H-thiazolo[5.4
-b] Azevin, allyl bromide and potassium carbonate were reacted, and the purified product was neutralized with hydrogen chloride to obtain the title compound (yield 56.4%). Melting point 162-163° (recrystallized from ethanol-ether) r R (K B r) cm-': 2934, 2
346, 1589, 1501, 1439, 125
4, 1132. NMR (d.-DMSO) δ: 1.54-1.68
(2H, m), 1. 73-1. 88 (2H, m)
．． 2. 17 (3H, s), 2. 81-2.
90 (2H, m), 3. 09-3. 18 (2H,
m), 3. 74-3. 89 (5H, m),
5. 26-5. 40 (2H, m). 5. 83
-6. (r2(fH, m), 6.97(IH.
d, J = 9Hz). 7. 14 (IH. d
, J=16Hz), 7. 30 (IH, d,
J= 16}1z), 7. 41-7.45 (2H,
m). Elemental analysis value: C. Calculated value as H,,N,OsCQ:
C, 63.73; H, 6.68; N, 7.4
3:S, 8, 51; CQ. 9.41. Actual value: C, 63.79; H, 6.60; N
, 7.41; S, 8.51: Cf2, 9.49.
Example 82 2-(2,6-difluorophenyl)-4-methyl-5
．． 6,7.8-Tetrahydro 4H-thiazolo[5.4
-b]Azepine hydrochloride By the same method as in Example 80, l-(2,6/fluorophenyl)-5.6,7.8-tetrahydride-4H-
React thiazolo[5.1-b]azepine, methyl iodide and potassium carbonate, neutralize the purified product with hydrogen chloride,
The title compound was obtained (yield 44.3%). Melting point 132-1
33° (recrystallized from methanol ether). I R (K B r) cm-': 2396, 1
622, 1585, 1530, 1470.101
1. 806 N M R (C D C C3) δ: 1. 70
-1. 82 (2H, m), 1, 912. 04
(2H, m), 3. 09 (3H, s), 3,
20 (2H, t, J=5Hz), 3. 37 (2
H, t, J = 6Hz). 7. 12 (2H,
t, J = 8Hz), 7. 457. 60(
IH, m) Elemental analysis value・Calculated value as C,,H,,N,S F,Cff・C, 53.0g. H 4.77;
N, 8.84. S, 10.12. F, 11.99;
Cff, 11.19. Actual value: C, 53.16.
H, 4.71. N, 8.86: S, 10.26
; F, 12.10; (1!, 11.15. Example 83 2-(2.6-difluorophenyl)-4-ethyl-5
．． 6,7.8-Tetrahydro 4H-thiazolo[5.4
-b] Azebin By the same method as Example 80, 2-(2.6difluorophenyl)-5.6,7.8-tetrahydride-4H-
Thiazolo[5.4-b]azevin, ethyl bromide and potassium carbonate were reacted to obtain the title compound (yield 4.2
%). Melting point 51-52° (recrystallized from ethanol-water)
．． I R (K B r) cm-': 1524, 1
498, 1461, 1432, 1371,992
, 796. NMR(CDC(!3)δ 1.25(3H, t
, J = 8Hz), l. 501. 98 (4H
, m), 2. 92-3. 09 (4H, m),
3. 24 (2H, q, J = 8Hz), 6,
95-7. 40 (3H, m). Elemental analysis value: C
Calculated value as IsH 8aN ts F t: C, 6
1.20; H, 5.48; N, 9.52; S,
10.89; F, 12.91. Actual value: C, 61
．． 04; H, 5.40; N, 9.58; s, t
o. 63; F, 13.06. Example 84 4-aryl-2-(2,6-difluorophenyl)5,
6,7.8-Tetrahydro 4H-thiazolo[5.4-
b] Azepine By the same method as Example 80, 2-(2.6difluorophenyl)-5.6,7.8-tetrahydride-4H-
Thiazolo[5.4-b]azepine, allyl bromide and potassium carbonate were reacted to obtain the title compound (yield 44.
3%). Melting point 68° (recrystallized from petroleum ether). I R (K B r) cm-': 1531, 1
467, 1412. 1352, 1243,100
8 NMR (CDCI2-) δ: 1.62-1.90 (
4H. m), 2.993. 09 (4H, m), 3
．． 78-L 82 (2H, m). 5. 25(I
H, dd, J = 2Hz, 10}1z), 5
．． 32 (IH, dd, J= 2Hz, 10Hz
), 5. 84-6. 04 (IH, m), 6.
93-7. 02 (2H, m), 7. 19-7
．． 28 (IH, m). Elemental analysis value: CIllHI.
Calculated value as N2SF: C, 62.72: H,
5, 26; N, 9.14; S, 10, 47; F
, 12.40 Actual value: C, 62.87; H, 5.24. N
,9.14. S, +0.48; F, 12.30. Example 85 4-(ethoxycarbonylmethyl)-2-(4methoxyphenyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine hydrochloride By the same method as in Example 80, 2-(4-methoxyphenyl)-5.
6,7.8-Tetrahydro 4H-thiazolo[5.4-b
]Azepine hydrochloride, ethyl bromoacetate and potassium carbonate were reacted and purified, and the product was neutralized with hydrogen chloride to obtain the title compound (yield 20.1%). Melting point 1 1C) -. 1
1 1' (recrystallized from methanol-ether). I R (K B r) am-': 1733, 1
596, 1531. 1271, 1260.118
g. NMR (d.-DMSO) δ: 1. 34 (3tl
, t, J=7Hz), 1. 69-1. 96(
4H, m), 3. 25-3. 30 (2H, m
), 3. 35-3. 40 (2H, m), 3.
87(:{H, s), 4. 01(2}1, s
), 4. 30 (2H, q, J=7Hz),
7. 02 (2H, d, J = 9Hz), 8.
22 (2t{, d, J = 9Hz). Elemental analysis value: C,. H,. N.O. Calculated value as SCQ: C
,56.46. H. 6.05; N, 7J2; S
．． 8J7: CI2, 9.26. Actual value C, 56
．． 61;H. 5.83: N, 7.38; S,
8.40: CC, 9.19 Example 86 4-acetyl-2-(35-di-tert-butyl-4
-hydroxy7phenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5,4-b]acepine Example 40
2-(3.5-7-t-butyl-4-hydrocyphenyl)-5.6.7.8-tetrahydro-4H-thiazolo[5.4b]acepine, triethylamine and acetic anhydride :) The title compound was obtained (yield 560%). Melting point 198-199°I R (KBr)Cm-': 3542, 2
954, 2924, +666. 1406.138
5 1107 NMR (CDCQ3) δ l. 4g (188, s
), 1. 58-2. 02 (4IL m) 2.
13 (3H, s), 2. 93 (2H, t),
3. 68 (2H, t), 5. 45 (IH.s
), 7. 88 (2H, s). Elemental analysis value: C
, 3H 32N , Calculated value as S○2 C, 6g. 9
6. H, 8.05. N, 6.99: S, 8.0
0? Measured value: C, 6g. 78; H, 7■99; N
, 6.70S 8.00. Example 87 2-(3-methoxy4-methylthiomethoxystyryl)-5.6,7.8-tetrahydro-4Hthiazolo[5
．． 1-b] Acepine The title compound was obtained from 3-methoxy-4-methylthiomethoxycinnamic acid, 3-amino epsilon-caprolactam and phosphorus pentasulfide in the same manner as in Example 18 (yield: 10.
7%). Melting point 117119° I R (K B r) cm': 1533, 1
509, 1445, 1370, 1256. N M
R (C D C I23) δ: 1. 67 (2
H, m), 1. 82 (2H, m), 2. 27
(3H, s), 2. 89 (2H, t), a.
12 (2H, t), 3. 90 (3H, s),
5. 26 (2H, s), 6. 99 (5H,
m). Elemental analysis value: C 1aH 22N 2S! 0
Calculated value as 2・C, 59, 64; H, 6.12
; N, 7.73S 17.69. Actual value: C, 59.57; H, 6.22; N
, 7.55; S, 17. 62 Example 88 2-(4-hydroxy-3-methobovcystyryl)-5.
6,7.8-Tetrahydro-4H-thiazolo[54-b
]Azepine Example 87 2-(3-Methoxy4methylthiomethoxy/styryl)-5.6,7.8 tetrahydride-
4H-thiazolo[5.4-b]azevin I. 88 g was dissolved in a mixed solution of dimethylformamide, acetonitrile, and water, and 11 g of mercuric chloride 2 was added thereto, followed by refluxing for 15 hours. After the reaction, add heavy water to chloroform-meth/
- Extracted with After drying with anhydrous magnesium sulfate,
The solvent was distilled off under reduced pressure. The residue was purified by column chromatography [chloroform-methanol (98:2
, v/v) to obtain 318 mg of the title compound.

Melting point 175-178° I R (K B r) cm-': 3394, 1
549, 1515, 1462. 13691263
1036 N:vlR(CDC(!+)δ: 1.67(2H
m), 1, 83 (2H, Il1), 2. 90(
2H, t), 3. 12 (2H, t), 3.
90 (IH, s), 3. 91 (3B, s),
6. 85-7. 05 (51 m) Elemental analysis value: C
+eH +eN 2SO 2・0. Calculated value as 5H,O: C, 61.71; H, 6.15;
N, 9.00. S, 10. 30. Actual value: C, 62.12; H, 5.90; N
, 8.91S, 10. 45. Example 89 2-(2-bilazinyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azevin Example 18
The title compound was obtained from 2-virazinecarboxylic acid, 3-amino-epsilon-caprolactam and phosphorus pentasulfide (yield 349%). Melting point 196198° (recrystallized from ethyl acetate). I R (K B r)ci+-': 3298,
1485, 1353, 1291. 1146753
．． N M R (C D C I23) δ: 1. 7
3 (2H, m), 1. 86 (2H, m) 2.9
8 (2Lt), 3. 17 (2H, t), 4.
29(I}l, brs), 8. 43 (211,
s), 9. 26 (IH.s). Elemental analysis value: C. Calculated value as H l2N *S:
C, 56.87; H, 5.21; N, 24,
12;S, 13. 80, Actual value: C, 56.97. H, 5.23; N
, 24.03;S, 13. 86, Example 90 2-(2-indolyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine Example 18
Indole 2-carphonic acid, 3-
The title compound was obtained from the amino-epsilon lactam and phosphorus pentasulfide (yield 353%). Melting point 198-200
° I R (K B r) cm-': 3226, 1
551, 1503, 1456, 1366, 135
3. 129g, 1257. 1142NMR (d.
-DMso)δ: 1. 63 (2H, m), 1
．． 74 (28, m), 2. 84 (2H, t),
3. Of(2H, t), 6. 63 (IH,
s), 6. 917. 14 (2H.m), 7.
38 (IH, d, J = 7.65Hz),
7. 47 (IH, d) II. 46 (IH, br
s) Elemental analysis value Calculated value as C15H,,N3S: C,
66.88; H, 5.61; N, 15.60;
S, I1. 90. Actual value: C, 66, 91; H, 5.53; N
15.4OS 11.92 Example 91 2-(4-dimethylaminophenyl)-5.6.78-
Tetrahydro-4H-thiazolo[5.4-b]azepine By the same method as in Example 18, the title compound was obtained from 4-dimethylaminobenzoic acid, 3-amino-epsilon monocab lactam and phosphorus pentasulfide (harvested rate II.5%). Melting point 1
52-154° (recrystallized from ethyl acetate) I R (K B r) cm'-': 3252,
1609, 1557, 1524. 14g3,14
67, 1444, 1358, 1269. 1+7
0. N M R (C D C f!+) δ: 1.
68 (2H, m), 1. 81 (2H, m)2
．． 92 (2tLt), 3. 08 (2H.t)
, 2. 98 (6H.s), 6. 68 (2H.
d, J=9, OHz), 7. 64 (2tL
d). Elemental analysis value: C, 5H. ．． Calculated value as N3S: C, 65.90; H, 7.00; N,
15.37; 3 11.73 Actual value: C, 65.90; H, 6.89; N
, 15.25. S, 12. 03, Example 92 2-(4-Methylthiostyryl)-5.6,7.8=tetrahydride-4H-thiazolo[5.4-b]azebin By the same method as in Example 18, 4-methylthiostyryl The title compound was obtained from cinnamic acid, 3-amino-ε-cabrolactam and phosphorous pentasulfide (yield 575%). Melting point 1571
59°. I R (K B r) cm': 3260, 1
621, 1545, 1430, 1353, 109
1 949. N M R (C D C C3) δ: 1. 67
(2H, m), 1. 82 (28, m), 2.
49 (3H, s), 2. 89 (2H, t),
3. 11 (2H, t), 7. 01(2H, q
), 7. 2] (2H, d, J = 8.5H
z), 7. 38 (2H, d). Elemental analysis value: C
, 6H 1-N-S Calculated value as t: C, 63.5
4; H a. oo; N, 9.26.3 21
．． 20 Actual measurement: C, 63J1; H, 5.92: N,
9.27:S, 21. 36 Example 93 2-[1-(2-furyl)ethenyl]-5.6,7.8
-tetrahydride-4H-thiazolo[5.4-b]azebin The title compound was prepared from β-(2-phenol)acrylic acid, 3-amino-ε-cabulactam, and phosphorus pentasulfide in the same manner as in Example 18. (yield 14.0%). Melting point 125-128°, I R (K B r) cm-':
3260, 1547, 1422, 1351 9
44 736. NMR (CD Cf2.) δ:
1.68 (2H, m), 1.81 (2H, m)2. 8
9 (2H, t), 3. 11(2H, t), 6
．． 40 (2H, m). &． 91 (2H, q)
, 7. 40 (IH, d) Elemental analysis value: Calculated value as C,, H,, N, SO ・C, 63.39; H, 5.73; N, 1
1.37S 13.02, Actual value: C, 62.87; H, 5.58+N
, 11.17S L3.46. Example 94 2-[2-(4-methquinphenyl)ethyl 1-56.
7.8-Tetrahydro-4H-thiazolo[5.4b]azepine The title compound was obtained from 4-methoxyphenylpropionic acid, 3-amino-epsilon-lactam and phosphorus pentasulfide in a manner similar to Example 18. (yield 26.0%).

Melting point 80-83° I R (K B r) cm-': 1612, 1
584, 1513, 1486, 1437, 124
7. 1178, 1037. NMR (CDCf23) δ: 1,64 (2H, m)
, 1.79 (2H, m), 2. 83-3.10 (12
[1, m), 3. 79 (3Fl, s), 6.
84 (2H, d, J=8.6Hz), 7. 1
4 (28, d). Elemental analysis value: C, 8H 20N
Calculated value as 2S O ” O, 5H , O C, 6
4.61; H, 7.12; N, 9.42; S
, 10. 78 Actual value: C, 64.86. H, 6.87. N
, 9.48S, 11. 02 Example 95 2-(4-biphenylyl)-5.6.7.8-tetrahydro-4H-thiazolo[5.4-b]azebin 4-phenylbenzoic acid, 3 The title compound was obtained from -amino-ε-cabrolactam and phosphorus pentasulfide (yield 60.0%). Melting point l80-
183°. I R (K B r) cm-': 3232, 1
520, 1490, 1445, 1371,765
, 692. NMR (CD Cff3)δ: 1. 71(2
H, m), 1. 84 (2H, m), 2. 97
(2B, t), 3. 13(2H.t),'y
．． 30-7. 50 (3H, m), 7. 61(
4H, m), 7. 84 (2B, d). Elemental analysis value: C. @H,. N. Calculated value as S: C,
74.47; H, 5.92; N, 9.14S
, 10. 46 Actual value: C, 74.04; H, 5.78; N
, 8.86;S, 10. 66. Example 96 2-(4-dimethylaminostyryl)-5.6.78-
Tetrahydro-4H-thiazolo[5.4-b]azebin The title compound was obtained from 4-dimethylaminocinnamic acid, 3-amino-epsilon-cafrolactam, and phosphorus pentasulfide in the same manner as in Example 18 (yield: l6.3%). Melting point 2
07-210' (recrystallized from ethyl acetate). I R (K B r) cm-': 3274, 1
604, 1548, 1525, 1443, 136
5, 1165. N M R (C D C Qs) δ: 1. 67
(2H, m). 1. 81 (2H, m), 2.
88 (2H, t), 3. 09 (2H, t),
2. 98 (6H, s). 6. 68 (2H, d
, J = 8. 91Hz). 6. 93 (2H,
d), 7. 36 (2H, d). Elemental analysis value: C
,7H,,N3S-0.4H. Calculated value as O: C,
66.59;H. 7.17; N, 13.70;
S, 10. 46. Actual value: C, 66.77: H, 6.93; N, 1
3.62;S, 10. 85. Example 97 2-(3-dimethylaminophenyl)-5.6,7.8
-Tetrahydro-4H-thiazolo[5.4-b]azepine The title compound was obtained from 2-dimethylaminobenzoic acid, 3-amino-epsilon-cabrolactam and phosphorus pentasulfide by a method similar to Example 18 (yield 34.9%). Melting point 1
64-166° (recrystallized from ethyl acetate). I R (K B r)cn+': 3228,
1599, 1557, 1502, 1436, 13
71. 1a56, 1267. NMR (CDCl23) δ: 1. 69(2}1,
m), 1. 83 (2H, m), 2. 95 (2
H, t), 3. 10 (2H, t), 2. 9
9 (6H, s), 6. 71 (LH, d), 7
．． 04-7. 29 (3H, m). Elemental analysis value:
C,5H,. Calculated value as N3S: C, 65.
90; H, 7.00: N, 15.37; S,
11. 73. Actual value: C, 66.06; H, 6.99; N
, 15J2;S, 11. 86. Example 98 2-[3-(2-methylthio)pyridyl]-5.67,
8-Tetrahydro 4H-thiazolo[5.4b]azevin dihydrochloride. In the same manner as in Salt Example 18, 2-(methylthio)nicotinic acid, 3-amino-epsilon-cabrolactam and phosphorus pentasulfide were reacted, and after purification the raw material was neutralized with hydrogen chloride to obtain the title compound ( yield 61.3%). Melting point 142-145
°, I R (K B r) cm-': 3424, 1
601, 1519, 1466, 1434, 137
1.124g. NMR (d.-DMSO) δ: l. 70 (2H,
m), 1. 91 (2H, m), 2. 58 (3
H, s), 2. 98 (2H, t), 3. 1
8 (2H, t), 7. 28 (IH, dd),
8. 16 (IH, d, J = 7.73Hz),
8. 55 (IH, d, J-4.76Hz) Elemental analysis value: C,. H,,N. Calculated value as S2CQ2: C, 44, 57; H, 4.89; N
, 11.99. S, 1g. 31; CC, 20.24
．． Actual value: C, 44.25; H, 5.03;
N, 11.55; S, 17.96: C&, 19.60 Example 99 2-(4-diethylaminostyryl)-5.6.78-
Tetrahydro-4H-thiazolo[5.4-b]azepine By a method similar to Example 18, the title compound was obtained from 4-diethylaminocinnamic acid, 3-amino-epsilon-cabulactam and phosphorus pentasulfide ( yield 230%). Melting point 1
71175° (recrystallized from ethanol) I R (K B r) cm-' + 3280. 1
601, 1547, 1524. 13541272
, 1254. 11g1, 1158. 962NM
R(CDCl23)δ: 1. 17 (6H, t)
, 1. 65 (28, m), 1. 81 (2H,
i), 2, 87 (2H.t), 3. 09 (2H
, t), 3. 37(41{, q)6. 64(
2H, d, J = 8. 61Hz), 6. 9
1 (2H, d), 7. 33 (2Hd). Elemental analysis value: C,. Calculated value as H,5N3S: C
,69,68; H,7.69; N,12.83
;S, 9.79. Actual value: C, 69, 75; H, 7.76; N,
12.69S, 9.72 Example 100 2-(4-methylaminophenyl)-5.6,7.8-
Tetrahydride-4H-thiazolo[5.4-b3 azepine dihydrochloride By the same method as Example 18, 4-methylaminobenzoic acid, 3-amino-epsilon lactam and phosphorus pentasulfide were reacted and purified. The product was neutralized with hydrogen chloride to give the title compound (35.5% yield).

Melting point 222-225°. I R (K B r) cm-': 3198,
1600, 1527. 1499NMR (CDCQ3
) δ: 1. 64 (2H, m), 1. 75 (
2H, m), 2. 78 (3H, s). 2. 9
5 (2H, t), 3. 06(2t{, t),
a. 78 (2H, d, J = 7.25Hz),
7. 86 (2H, d). Elemental analysis value: C,.
H. N. S Calculated value as CI22: C, 50.
60; H, 5.76; N, 12.65. Actual value: C, 50.80. H, 5.78; N, 12
．． 54. Example 101 1-(2-methoxytrans-styryl)-5.6,
7.8-Tetrahydro 4H-thiazolo[5,4-b]
The title compound was obtained from cis-2-methoxycinnamic acid, 3-amino-ε-monolactam, and phosphorus pentasulfide in the same manner as in Azevin Example 18 (yield: 32.1%). Melting point 1
67i70' (recrystallized from ethyl acetate). IR(KBr)cII1-': 3278,
1616, 1596, 1539. 1492,1
464, 14:{1, 1366. 1246, 1
105, 1024, NMR (CDCI23) δ:
1. 68 (28, s+), 1. 80 (2H,
m), 2. 89 (2H, t), 3. 11 (2H
, t), a. 8g (3H, s), 6, 86 (
6H, m). Elemental analysis value: C,. H. Calculated as N 2 SO: C, 67.10. H, 6.33; N,
9.78.7 53 s. ii. 20. Actual value: C, 66.91; H, 6.30; N
,9.64;S,11,38, Example 102 2-(2-amino-5-methylphenyl)-5.6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azebin By the same method as in Example 18, the title compound was obtained from 2-amino-5-methylbenzoic acid, 3-amino-epsilon-cabrolactam and phosphorus pentasulfide, yield 12 .6%).

Melting point 113-115° (recrystallized from ethyl acetate). r
R(KBr)cII1-': 3404,
3350, 3296, 1623. 1558150
6, 1466, 1365, 1258. 1161
．． NMR(CDC(!s)δ: 1.68(2H,
m), 1. 82 (2H, m), 2. 24 (3
H. s), 2. 90 (2H, t), 3. 1
0(2H, t), a. 63 (IH. d, J =
8.111z>. 6.89 (l}l, dd), 7.1
8 (IH, d, J = 1.49Hz) Elemental analysis value:
Calculated value as C, 4H, 7NffS・C, 64, 83;
H, 6.61; N, 16, 20; S1236, Actual value: C, 64.86; H, 8.59; N
, 16.43; S, i2. 36 Example +03 2-(3-amino-4-methylphenyl)-5,6.7
．． 8-Tetrahydro-4H-thiazolo[5,4b]acepine The title compound was obtained from 3-amino-4-methylbenzoic acid, 3-amino-epsilon-cabrolactam and phosphorus pentasulfide in the same manner as in Example 18. (Yield 328%).

Melting point 135-137° l R (K B r) cm-': 3436, 3
332, 3226, 1634, 1561, 150
0, 1460, 1441. 13681258,N
M R (C D C Q3>δ: 1.6g(
2H, m), 1. 82 (2H, m), 2. 1
7 (3H, s), 2. 93(2H, t), 3
．． 10 (2H, t), 3. 60(21+,br
s), 7. 04 (1.H, s), 7. 10(
2H, d) Elemental analysis value: C,. Calculated value as H,,N3S: C, 64.83; H, 6.61;
N, 16, 20; S, 12. 3B. Actual value: C, 64, 58; H, 6.60; N,
16.04;S, 12. 12. Example 104 2-(2-amino-4-ylolophenyl)-56.7.
8-tetrahydro-4i{-thiazo O [5. 4b
] The title compound was obtained from 2-amino/4-chlorobenzoic acid, 3-amino-epsilon monocab lactam and phosphorus pentasulfide in the same manner as in Azebin Example 18 (yield 6.7%).

Melting point 154-157° I R (K B r) am"-': 3450,
3384, 1610, 1557. 1491146
5, 1371, 1264, 1148, 1064
．． NMR (CDCf!.) δ: 1. 6g (2H,
m), 1. 82 (2H, m)2. 89 (21
{, t), 3. 10 (2H, t), 3. 9
5 (1H, brs), 6. 12(2t(brs)
, 6. 60 (18, dd), 6. 69 (IH
, d, J = 1. 91Hz), 7. 26(
IH, d, J=8. 43Hz). Elemental analysis value:
C,3H,. Calculated value as N3S CC: C,
55.81; H, 5.04; N, 15.02;
S, 11.46; Cff, +2.67, actual value:
C, 55.70; H, 5.02; N, 14.8
7;S, 11.49. CI2, 12.65 Example 1
05 2-(4-thioacetami/phenyl)-5.6,7,
8-Tetrahydro-4H-thiazolo[5.4-b Coasepin By the same method as in Example 18, the title compound was obtained from 4-acetamy7benzoic acid, 3-amino-ε-cabrolactam and phosphorus pentasulfide ( yield 103%).

Melting point 239-242° I R (K B r) cm-': 3434, 15
51, 1515 1496, 1454, +370. NMR (d8-DMSO) δ: 1.59 (2H, m
), 1.72 (2HII+). 2. 62 (311,
s), 2. 80 (2H, brs), 2. 9
8 (211, brs)6. 25(I}].br
s), 7. 70 (2H, d, J = 8.6
5Hz). 7. 89 (2H, d), 11. 65
(1}1.brs) Elemental analysis value: C I58 I7
Calculated value as N 33 2: C, 59.37; H
, 5.65; N, 13.85; S, 21. 1
3. Actual value: C, 58.92; H, 5.66; N
, 13.55; S, 21. 23 Example 106 2-(3-amino-4-methylphenyl)-5.6,7
．． 8-tetrahydride-4H-thiazolo[5,4-b]azepine dihydrochloride 3-amino-4-methylbenzoic acid, 3-amino-ε~cabrolactam and phosphorus pentasulfide were reacted in the same manner as in Example 18. After purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield 364%).

Melting point 170i73° I R (K B r) cm-': 1604, 1
561, 1528. 1453, 1371. NMR
(d.-DMSO) δ: 1,66(2H,m),1
．． 83 (2H, m), 2. 41 (3H, s),
2. 92 (2H, t), 3. 10(2H, t
), a. 35 (2H, brs), 7. 37(
IH, s, J=8. 05Hz), 7. 72
(2H, d), 7. 90(l}l, s). Elemental analysis values: C,4H,. N3S Cl22.0
．． Calculated value as 5H, O, C, 49.27: H, 5.91. N
, 12.31; S, 9.40; Cff 20
．． 77. Actual value: C, 49.20; H, 5.57
; N, 12.36; S, 9, 53; C c
, 20. 86 Example 107 2-(2-pyrrolyl)-5.6,7.8-tetrahydro. 4 H-thiazolo[5.4-b]azevin dihydrochloride By the same method as in Example 18, virol-2 carboxylic acid, 3-amino-ε-monocuboid lactam and phosphorus pentasulfide were reacted, and the purified product was purified. Neutralization with hydrogen chloride gave the title compound (yield 18.6%).

Melting point] 10-113° (recrystallized from methanol),
I R (K B r) am-': 3430, 1
631, 1611, 1454, 1372, 105
5. N M R (C D C Q3') δ: ]. 6
7 (2H, m). 1. 74 (2H, m), 2.
84 (2H, t), 3. 08 (2+1, t)
, 6. 33 (IH. dd), 7. 10 (IH
dd), 7. 20 (IH, brs). Elemental analysis value: C IIH 15N3S Calculated value as CL: C
, 45.21; H, 5.17; N, 14.38
;S, 10. 97. Actual value: C, 45.46; H, 5.13; N
, 14.47;S, 10. 94 Example 108 2-(3-amino-4-methoxyphenyl)-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4b]acepine dihydrochloride 3-amino-4-methoxybenzoic acid, 3-amino-epsilon lactam and phosphorus pentasulfide were prepared in the same manner as in Example 18. After reaction and purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield 13.0%).

Melting point 194197° (recrystallized from methanol) I R
(KBr)cm-': 3318, 1603
, 1591, 1536. 1485,137+,
1352. 12g9, 1245, 1165. 1
035NMR (d.-DMSO) δ: 1.63 (2
H, m), 1.81 (28m), 2. 90 (2H,
t), 3. 08 (2tl, t), 3. 94
(3H, s), 6. 05 (2H, brs),
7. 27 (LH, d, J= 8.67}1z)
, 7. 81 (IH, dd)7. 88(I}l,
d, J=2. 12Hz), elemental analysis value: C
,,H,. Calculated value as N33 Cl2,0: C,
48.28; H, '5.50; N, 12.06
;S, 9, 21. Cff, 20.36. Actual value:
C, 47.80; H, 5.57; H, 11.
82; S, 9.23; Cff, 20.17. Example 109 2-(4-amino-3-methylphenyl)-5+6.7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azevin dihydrochloride 4-amino-3-methylbenzoic acid, 3-amino-epsilon-lactam and phosphorus pentasulfide were reacted in the same manner as in Example 18. After purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield: 11.3%).

Melting point 240-243° (recrystallized from methanol). I
R (K B r)am"-': 3246.2
582, 1607. 1521. 14951452
．． 1374. 1359. 818NMR(d..-
DMSO) δ: l. 63 (2H, m), 1.
76 (2H, m), 2. 29 (3H, s),
2. 92 (2B, brs). 3. 06 (2H.
brs), 6. 20 (2H, brs), 7.
18 (IH, d, J = 8.05Hz), 7
．． 71 (IHdd, J= 1.87Hz), 7
．． 73 (IH, brs). Elemental analysis value: C,.
H. Calculated value as N3S CN2: C, 50.6
0; H, 5.76; N, 12.65S, 9.
65; CI2, 21.34. Actual value: C, 50.
64; H, 5.85; N, 12.61. S,
9.81; Cff, 21.12. Example 110 2-(2-amino-6-methylphenyl)-56.7.
8-tetrahydride-4H-thiazolo[5.41b]azevin dihydrochloride 2-amino/6-methylbenzoic acid, 3-amino-epsilon-cabrolactam and phosphorus pentasulfide were prepared in the same manner as in Example 18. After reaction and purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield: 16.0%).

Melting point 189-192° (methanol or recrystallization), I
R(KBr)cm-': 3256. 28
04, 1482, 1603, 156L1531,
14H, 1446. 13'70, 1355.
1282. 1250NMR(d.-DMS○)δ:
1. 68 (2H, brs), ]. 7g (2H
, brs), 2. 22 (3H, s), 2.
89 (2H, t), 3. 11 (2H, t), 5
．． 40 (2H, brs), 6. 96 (IH,
d), 7. 05 (IH, d), 7. 30 (I
Ht). Elemental analysis value: C 14H 18N35 C (calculated value as 22: C, 50.60; H, 5.76.
N,! 2, 65; S, 9.65; Cl! ,21J
4. Actual value: C, 5G. 42; H, 5.93;
N, 12.43; S, 9.66; C (, 21.
22. Example III 2-methquinecarbonyl-5.6,7.8-tetrahytro-4H-thiazolo[5.4-b]azevin Example 2
The title compound was obtained from methyloxalyl chloride, 3-amino-ε-monolactam, and phosphorus pentasulfide in the same manner as in Example 3 (yield: 19.9%).

Melting point 166-168° (recrystallized from ethyl acetate). l
R(KBr)c+n-': 3412, 3
314, 3264. 1716, 1441.138
1 1241 NMR (d.-DMso) δ: 1.69 (2H, m
), 1.84 (28, m), 2. 98(21{,
t), 3. 17 (2H, t), 3. 93(3
H, s), 4. 46 (1H, brs). Elemental analysis value: Calculated value as C, H, N, O, S: C, 50.92. H, 5.70. N. 1
3.20;S, 15. 11. Actual value: C, 50.98; H, 5.71; N
, 13.22;S, 15. 25 Example 112 2-(2-amino-3-methylphenyl)-5,6,7
．． 8-Tetrahydro 4H-thiazolo[5,4-b]azepine dihydrochloride 2-Amino-7-3-methylbenzoic acid, 3-amino-epsilon-cabrolactam and phosphorus pentasulfide were reacted in the same manner as in Example 18. The title compound was obtained by neutralizing the purified raw extract with hydrogen chloride (yield: 38.2%).

Melting point 208-211° (recrystallized from methanol) T
R(KBr)am-': 342g, 157
g, 1542, 1513. 14681308,
1273. NMR (do-DMSO) δ: 1. 66 (2H,
m), 1. 81 (2H, m). 2. 35 (3
H, sl2. 90 (2H, t). 3. 08(
2H, t), a. 29 (2H, brs), 7
．． 07 (IH, t), 'y. 22 (1B, d
). 7. 42 (IH, d). Elemental analysis value: C
、． H. N. Calculated value as S Bff, C, 50
．． 60; H, 5.76; N, '12.65; S
, 9.65; C&, 21, 34. Actual value: C,
50.69; H, 5.73; N, 12, 58;
S, 9.64; CQ, 21.41. Example 113 2-(2-amino-4,5-dimethoxyphenyl)-5
．． 6.7.8-Tetrahydro-4H-thiazolo[5.4
-b] Azevin dihydrochloride 2-amino-4,5-
Dimethoxybenzoic acid, 3-amino-[epsilon], Kabuguchi lactam, and phosphorus pentasulfide were reacted, and the purified product was neutralized with hydrogen chloride to obtain the title compound (yield 3.9%).

Melting point: 194-197° (recrystallized from methanol). I
R(KBr)cm-': 3444, 16
04, 1531, 1462, 1447, 1396
．． 1362, 1300. 127g, 1262.
1212, 1140, 1079. NMR (d.-
DMSO) δ: 1.63 (2H, n+), 1.82
(2B, m). 2. 92 (2H, brs), 3
．． 07 (2tl, brs), 3. 81 (3H,
s), 3. 85(:3H, s), 7. 06(
IH, s), 7. 10 (IH, s), 7.
10 (2H, brs). Elemental analysis value: C. ,H,. N. SO,CQ,
Calculated value as C, 47.62; H, 5.59;
N, 11.11; S, 8.48: (1!, 11
74 actual value: C, 47.54; H, 5.74;
N. 10.98. S, 8,19; CI2,18
．． 54. Example 114 2-(3-amino-4-methylstyryl)-5,6,
7. 8-tetrahydro 4H-thiazolo[5,4-b
Coazepine dihydrochloride By the same method as in Example 18, 3-amino-4-methylcinnamic acid, 3-amino-ε-cabrolactam and phosphorous pentasulfide were reacted, and after purification, the product was neutralized with hydrogen chloride to obtain the title A compound was obtained (yield 11.8%).

Melting point 244-247° (recrystallized from methanol). I
R(KBr)am"-': 3446, 3
248, 1604. 1518. 1502, 144
5, 1372, 1356, 1309, 956,
883, 818. NMR (d.-DMSO-D,O
) δ: 1.69 (4Lm), 2. 37 (3H,
s), 2. 82 (2H, brs), 3. 08
(2H. brs), 7. 32 (2H, d),
7. 39 (IH, d, J = 8.06Hz),
7. 60 (IH, d), 7. 63(IH,s
). Elemental analysis value: C,. H2,N3SCl2. Calculated values as: C, 53.63; H, 5.91; N, 1
1.73; S, 8.95; Cl2, 19.79.
Actual value: C, 53, 47; H, 5.79; N,
11.73. S, 8.95-CR, 19.54.
Example 115 2-[2-(6-methyl)pyridyl]-5.6.7.8
-Tetrahydro4 8-thiazolo[5.4 -b]acevin hydrochloride 6-methylbicolinate, 3-amino-ε-cabrolactam and phosphorus pentasulfide were reacted in the same manner as in Example 18, and the purified product was chlorinated. Neutralization with hydrogen gave the title compound (yield 40.8%).

Melting point 185-188° (recrystallized from methanol). I
R (K B r) cm': 3444, 32
12, 1582, 1567, 1533.1456
+370.1350. NMR (d.-DMSO-D20) δ: 1.68 (
2H, m), 1. 80 (2H, m), 2. 61
(3H, s), 2, 93 (2H, t), 3.
12 (2H, t), 7. 39 (18, d, J
= 7. 36Hz), 7. 87 (IH, d,
J = 7. 77Hz), 8. 00(In, t)
．． Elemental analysis value: C. ,H. ,N. S Calculated as CI2: C, 55.41; H, 5.72. N
, 14.91;S, 11. 38: C f2,
12. 58. Actual value: C, 55JO; H, 5
．． 64; N, 14.82; S, 11. 46;
CQ, 12. 18. Example 116 2-(3-cyanophenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azebin 3-(3-cyanobenzoyl)
The title compound was obtained from amino-ε-caprolactam and phosphorus pentasulfide (yield 41.5%). Melting point 174° (recrystallized from ethyl acetate). I R (K B r)cm""
: 2914, 222g, 1523, 1483,
1461.1370,802. NMR (CDCl23) δ: 1. 67-1. 9
1 (4H, m), 2. 922. 98 (2H,
m), 3. 14 (2H.t, J = 5Hz)
, 7. 45 (IH, t, J7Hz), 7.
55 (IH. m). 7. 96 (IH, m),
8. 04-8. 06 (IH, m) Elemental analysis value:
C. ．． 8. Calculated value as 3N3S: C, 65.8
5. H, 5.13. N, 16, 46S, 1
2. 56 Actual value: C, 65.91: H, 5.05: N
, 16.65. S, 12. 53 Example 117 2-(4-anophenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azepine 3-(4-cyanobenzoyl) )
The title compound was obtained from amino-ε-cabrolactam and phosphorus pentasulfide (yield 57.3%). Melting point 163-164°
(Recrystallized from ethyl acetate). I R (K B r)a
m': 2222, 1507, 1439, 11
73, 1356, 834. NMR (CDCI2s) δ: 1.60-1.91 (
4H, +n), 2.96 (2H, t, J= 6Hz)
, 3. 15 (2H, t, J = 5Hz),
4. 10 (IFI, br. s), 7. 63(2
H, d, J = 8t{z), 7. 84 (2H
, d. J=8Hz). Elemental analysis value: C,. H
,, Calculated value as N3S: C. 65.85; H
, 5.13; N, 16.46; 3 12.56 Actual value: C, 66.15; H, 4.93; N
, 16.52;S, 12. 4B. Example 118 2-[2-(4-imidazolyl)ethenyl]-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4-b]
Azepine dihydrochloride The title compound was obtained from imidazole 4-acrylic acid 3-amino-epsilon-cabrolactam and phosphorus pentasulfide in the same manner as in Example 18 (yield 12.2%). Melting point 170-173° (recrystallized from methanol). I R (K B r) cm-': 3326, 2
746. 1597, 1513, 1450, 137
5. 1348. NMR (d.-DMS O-D,O) δ: 1
．． 57-1.92 (4H, i), 2. 86 (2H
, I1), 3. 11 (2H, n+), 7.
25 (IH, d. J = 16.7Hz), 7.
49 (IH, d. J= 16.7Hz). 7
, 88 (IH, s), 9. 17 (IH, s). Elemental analysis values: C,,H. ．． N. S CQ.・0.
5H. Calculated value as 0: C, 43.91; H, 5.22; N
, 17.07; S, 9.77; CQ, 21.6
0 actual value: C, 44.08. H, 5.54.
N, 17.24; S, 9,66; Cl2,21
．． 23 Example 119 2-(4-ethoxyformimidoylphenyl)5,6
,7.8-tetrahydro-4H-thiazolo[E,4-b
Coazepine dihydrochloride 2-(4-na/phenynolene-5.6,7.8-tetrahydride-4H-thiazolo[5.4-b]azepine (8
．． An ethanol solution (700d) of OOg) was saturated with hydrogen chloride and left overnight. This was concentrated under reduced pressure, and the residue was washed with ether and dried to obtain the title compound as a powder with a melting point of 146° (decomposition) (115! amount: 10.9 g).
, yield 93%).

I R (KBr)cm': 1592. 152
9, 1495, 1443, 1352. 1071
NMR (d.-DMSO) δ: l. 40 (3H,
t, J = 7Hz), 1. 50-1. 90 (4
}1, m), 2. 82-2. 94 (2H, m
), 3, 01-3. 12 (2H, m>. 4.
66 (2H, q, J=7Hz), 7. 92(
28, d, J = 9}1z)8. 18 (2H,
d, J=9Hz). Example 120 2-(4-ethoxyformimidoylphenyl)-5.
6,7.8-tetrahydro4H-thia'noro[5.4
-b] azevin 2-(4-ethoxyformimidoylphenyl) 5.6
,7.8-tetrahydro-4H-thiazolo[54-b]
Azepine dihydrochloride (1.5 g) was neutralized with aqueous sodium bicarbonate and extracted with chloroform. The extracted layer was washed with water, dried, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound as a powder with a melting point of 14l-143° (yield: 1.1 g, yield: 87%).
.

I R (KBr)cm': 1625, 151
3, 1411, 1370, 1328, 1090
．． NMR (CDCf23) δ: l. 41(aH,
t, J-7Hzl 1. 571. 97(4}1,
m), 2. 89-3. 01 (2H, m),
3. 06-3. 17 (2H, m), 4. 32(
2H, q, J= 7Hz), 7. 76 (4H,
s). Example 121 2-(4-amidinophenyl)-5.6,7.8tetrahydro-4H-thiazolo[5.4-b]acevin dihydrochloride 2-(4-ethoxy/formimidoylphenyl)5 ,6
,7.8-tetrahydro-4H-thiazolo[5.4-b
]Azevin dihydrochloride (1.3g) in ethanol I solution (
150 m) was saturated with ammonia and left overnight. After filtering off the precipitate, the two-head solution was concentrated, and the residue was neutralized with hydrogen chloride to obtain the title compound (yield: 0.5 g, yield: 42%).

Melting point 2l8-2200 (recrystallized from methanol-ether) 5 r R (KBr) cm-': 3188. 167
1. 1596, 1502. 1369, 1450
．． 1438 NMR (d.-DMso) δ: 1. 56-1. 8
3 (4H, m). 2. 81-2. 90 (2H,
m), 3. 01-3. 11 (28, m),
7. 87 (2H, d, J = 9Hz), 7
．． 93 (2H. d, J = 9Hz) Elemental analysis value: C. 4H,,N4S・2HCl! Calculated value: C, 48.70; H, 5.25: N, 16.2
3S 9.29; Cl! , 20.53. Actual value:
C, 4g. 34;H. 5.31; N, 16.09;
S, 9.05; CI2, 20.31. Example 122')-(A-IIJ.'J-dimethylamidinophenyl)5,6,7.8-tetrahydro-4H-thiazolo[5
4-b]Azevin trihydrochloride 2-(4-ethoxyformimidoylphenyl)v +
6. 7,8-Tetrahydro-4H-thiazolo[5
．． 4-b] Ethanol solution of azepine (1.6 g) (7
0 mosquitoes) in 3.8M dimethylamine in toluene for 7 nights (1 mosquito).
．． 6m) was added and stirred at room temperature for 1 day. The reaction solution was concentrated, the residue was washed with ether, and then neutralized with hydrogen chloride to obtain the title compound (yield: 1.4 g, yield: 63%).
.

Melting point 193-196° (recrystallized from methanol-ether). I R (KBr) cm-': 3100, 246
4, 2238, 1664, 1625, 1533
, 1437. NMR (d.-DMSO) δ: 1. 49-1. 9
6 (4H, m), 2. 88-2, 97 (2H,
m), 3. 01-3. 26 (8R, m), 7
．． 69 (2H. d, J = 8Hz), 8.
00 (2H, d, J- 8Hz) Elemental analysis value: C
．． H -oN 4S ・3 H C Calculated value as Q: C, 46.89: H, 5.66: N, 13.6
7;8.711H:Cθ. 25. 95 Actual value: C, 46.71; H, 5.77; N, 1
3.36; S, 8.02; CC, 25.16 Example 123 2-(4-N-penzylamidinophenyl)-5.6,
7.8-tetrahydride-4H-thiazolo[5,4b]azepine dihydrochloride 2-(4ethoquinoformimidoylphenyl)-5.6,7.8-tetrahydride was prepared by the same method as in Example 122. -4H-thiazolo[5,ib]acepine was reacted with penzylamine, and the product was neutralized with hydrogen chloride to obtain the title compound (yield 38%).

Melting point 241-25i' (recrystallized from methanol/ether) I R (KBr)c+n '゜2998, 1667
, 1599, 1520, 1497, 1369,
747. N M R (do D M SO ) δ: l.
55-1. 90(4}1, m), 2, 812
．． 92 (2H.m), 3. 01-3. 26(
2H. m), 4. 73 (2H, d, J =
6Hz), 7. 38-7. 46 (5H, m),
7. 88 (4H, s). Elemental analysis value: C,,
H,,N. Calculated value as S・2HCC C, 57.
93; H, 5.56; N, 12.87; S, ?
．． 36; CQ, 16, 28. Actual value: C, 57.
48; H, 5.55; N, 12.76; S, 7
．． 48: CI2, 16.41. Example 124 2-(4-N-methylamidinophenyl)-5,6,7
．． 8-tetrahydro-4H-thiazolo[5,4b]azevin dihydrochloride 2-(4ethoxyformimidoylphenyl)-5.6,7.8-tetrahydro-4H-thiazolo [5.1-b] Azevin and methylamine (in methanol) were reacted, and the product was neutralized with hydrogen chloride to obtain the title compound (yield 17%).

Melting point +81-186° (recrystallized from methanol/ether), I R (KBr) cm': 30g6, 167
3, 1631, 1597. 151g, 1372
, 1355 1125. N M R (d6D M SO ) δ: 1.50-
1,91(4Fl.ml 2.862.97(2
H, m), 3. 00-3. 13 (5H, m)
, 7. 88 (4H, s). Elemental analysis value C,,H
、． N. S・2HCN-0.5H, Calculated value as ○: C, 4g. 91; H, 5.75; N, 1
5.21; S, 8.71; Cl! , 19.25. Actual value: C, 48.83; H, 5.58; N, 15
．． 29; S 8.96; CC, 19.09. Example 125 2-(3-ethquinformimidoyl phenyl) 5.6
, 7.8-tetrahydro 4H-thiazolo[5.4-b
] 2(3-anophenyl)-5.6,7.8-tetrahydride-4H was prepared in the same manner as azepine Examples 119 and 120.
The title compound was obtained from -thiazolo[5.4-b]azepine (yield 83 1%).

Melting point 141-143° I R (KBr)am-': 3218. 292
8, 1634, 1524, 1370. 1323
+071. NMR (CDCC3) δ: 1. 43 (3H, t,
J=7Hz), t. 511. 97 (4H,
m), 2. 86-3. 19 (4H, m), 3
．． 97 (IH, br. s) 4. 34 (2H,
q, J= 711z). 7. 39 (IH, t,
J = 8Hz), 7. 68 (1tl. di,
J=lHz, 8tlz), 7. 82 (IH,
dt, J = IHz. 8Hz), 8. 10-
Ill. 14 (1B.m). Example 126 2-(3-N,N-dimethylamidinophenyl)5,6
,7.8-tetrahydro-4H-thiazolo[5.4-b
]Azepine dihydrochloride By the same method as in Example 122, 2-(3ethoxyformimidoylphenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azepine and Dimethylamine (toluene solution) was reacted and the product was neutralized with hydrogen chloride to obtain the title compound (70% yield).

Melting point 203-205° (recrystallized from methanol-ether). I R (KBr) cm-': 3022, 166
3, 1631, 1601, 1517, 1373
．． NMR (d.-DMs○) δ: 1. 56-1.
85 (4H, m), 2. 832.91 (2H,
m), 2. 96-3. 08 (2H, m), 2
．． 99 (3H, s), 3. 25 (3H, s)
, 7. 52-7. 69 (2H, m), 7.
95-7. 99 (2H, m). Elemental analysis value: CI
Calculated value as llH20N4S '2HCQ''0.5HvO・C, 50.25; H, 6.06; N, 14
．． 65;S, 8.39. Cl2, 1g. 54.
Actual value: C, 50,59; H, 6.36; N, 1
4.60;S, 8.46; (J7,1g.43
．． Example 127? (3-N-methylamidinophenyl)-5,6,7.
8-tetrahydride-4H-thiazolo[5,4-b]azepine dihydrochloride 2-(3ethoquinoformimidoylphenyl)-5.6,7.8-tetrahydride was prepared in the same manner as in Example 122. -4H-thiazolo[5.4-b]azepine and methylamine (methanol solution) were reacted, and the product was neutralized with hydrogen chloride to obtain the title compound (yield 54%).

Melting point 205-207° (recrystallized from methanol ether), I R (KBr) am-': 3192, 305
4, 1678, 1602, 1515, 1371
．． NMR (d.-DMSO) δ month. 5g-1.
85 (4H, m), 2, 842. 95 (2H
, m), 3. 00-3. 10 (5H, m),
? , 64 (IH, t, J= 8Hz), 7.
73-7. 76(II{, m), 8. 03-8
．． 11 (2H, m). Elemental analysis value: C,,H
．． ．． N. Calculated value as S・2HC(・o.5H,o: C, 4g.91; H, 5.75; N, 1
5.21;S, +! ．． 71; CC, 19.25. Actual value: C, 4g, 55; H, 5.66; N, 15.
11;S, 8.65. CI2, 19.15. Example 128 2-(5-penzimidazolyl)-5.6,7.8tetrahydro 4H-thiazolo[5.4-b]azevin dihydrochloride 3-(5-penzimidazolyl) The title compound was obtained by reacting the imidazolecarponyl)amino-ε monocab lactam with phosphorus pentasulfide, and neutralizing it with hydrogen chloride after purification (yield 14%).

Melting point: 208-210° (recrystallized from methanol/ether) I R (KBr) cm-': 292g, 272
6, 1605, 1514, 1375. 81g.
NMR (dll-DMSO)δ: l. 56-
1. 86C4H. m), 2. 862. 93(
2H, ITl), 3. 02-3. 07(28,
m), 7. 89 (IH, d, J = 9Hz
), 7. 97 (18, dd, J= 2Hz,
9Hz), 8. 18 (IH, br. s), 9.
66 (LH, s). Elemental analysis value: C,. H. N. S・2HCf2
Calculated value as -HtO: C, 46.54; H, 4.74; N, 1
5.51; S, 8.88; Cff, 19.63
Actual value: C, 46.72; H, 4.92; N, 1
5.20; S, 8.95; CQ, 19.93.
Example 129 2-(3-biridyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azepine dihydrochloride 3-nicotinoylamino The title compound was obtained by reacting ε-1-cubic lactam with phosphorus pentasulfide, and neutralizing it with hydrogen chloride after purification (yield: 66.0%).
).

Melting point 199-200° (recrystallized from methanol-ether). I R (KBr)am-': 3202, 273
0, 2478, 1552, 1499, 1370
．． NMR (d.-DMSO) (5: 1.56
-1.84 (4B, m), 2.842. 91 (2H,
m), 3. 03-3. 08 (2H, m),
7. 99 (IH, dd, J=5Hz, 8Hz)
．． 8. 70 (IH, dt, J = 2Hz.
8Hz), 8. 76 (II. dd. J = 2Hz
, 5Hz), 9. 09(IH, d, J =
2Hz). Elemental analysis values: C, 2H. ．． N3S・2
Calculated value as HCQ: C, 47.37. H. 4.9
7. N, 13.81; S, 10.54; CN, 23
．． 31. Actual value: C, 47.43; H. 4.99:
N, 13.95S, 10.24; Cff, 22,9
1. Example 130 2-(3-aminomethyl-4-methylphenyl)-5.
6,7.8-tetrahydro 4H-thiazolo[5,l-
b] Azepine dihydrochloride 2-(3-cyano-4-methylphenyl)-5.
6,7.8-Tetrahydro 4H-thiazolo[5.4-b
] Azevin was obtained (yield 74.7%).

N M R (C D C 123) δ: 1. 71
(2H, m), 1. 84 (2H, m), 2.
55 (3H,,s), 2. 94 (2H, t),
3. 13 (2H, t), 7. 31 (IH, d
J=8. 42Hz), 7. 84 (1B, dd
, J = 1. 93, 8. 42Hz). 7.
98 (IH, d. J = 1.93Hz). Then 2-(3-anor-4-methylphenyl)-5.6,
7.8-Tetrahydro-4H-thiazolo[5,4-b]
Azepine (6.12 g) and cobalt chloride hexahydrate (1
A mixed solution of methanol/tetrahydrofuran d (30d/20d) containing 0.8 g) was cooled with water, and sodium borohydride powder (8.6 g) was added little by little thereto, followed by stirring at room temperature for 1 hour. 4N hydrochloric acid solution in the reaction solution? After making the mixture acidic by adding water, it was extracted with diethyl ether, and the aqueous layer was made alkaline with aqueous ammonia and extracted with chloroform. The extracted layer was dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure.

The residue was purified with a Silica gel column and neutralized with hydrogen chloride to obtain the title compound (yield 22.7%).

Melting point 245-248° (recrystallized from methanol). I
R (KBr)cm': 3232, 2932,
+608. 1530, 1499, 1447,l
372 NMR(DMSO)δ: l. 66
(2H, m), 1. 82 (2H, m)+2.
40 (3H, s), 2. 92 (2H, br.
s). 3. 09 (2B. br. s), 4. 0
8 (2H, br. s), 5, 59 (2H, br.
．． s), 7. 34 (IH, d, J=8.0
6Hz), 7. 80 (IH, d, J= 8.
06Hz). 7. 89 (IH, s). 8. 56
(IH, br.s). Elemental analysis values: C, 5H,. N3SCQt- 0.5H
．． Calculated value as O: C, 50.70. H, 6.24; N, 1
1.83. S, 9,02; Cff, 19.95.
Actual value: C, 50.33. H, 6.02; N, 1
1.74; S, 9.04; CQ, 19.62. Example 131 2-(4-cyano-3-methylphenyl)-5,6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azepine hydrochloride After reaction and purification of 4-cyano-3-methylbenzoic acid, 3-amino-epsilon-lactam and phosphorus pentasulfide in the same manner as in Example 18. The product was neutralized with hydrogen chloride to give the title compound (yield 57.4%).

Melting point 184-186° (recrystallized from methanol) I R
(KBr)cm-': 320g, 2514,
2224, 1593. 15+4 14861459
．． 1371. NMR (d..-DMS○) δ: 1. 63 (2H,
m), 1. 75 (28, m), 2. 51 (
3H, s), 3. 05 (2H, t), 5.
82 (IH, br. s), 7. 68 (IH,
dd, J=1. 44, 8, 16Hz), 7.
76 (LH, d, J = 8.16Hz), 7.
78 (LH, S). Elemental analysis value: C 1sH r#N ss Calculated value as Cβ: C, 5g. 91; H, 5.27; N, 1
3.74;S, 10. 4g; C 12, 11
．． 59. Actual value: C. 58.58; H, 5.22
; N, 13.59; S, 10. 20: C f
f, 11. 42. Example 132 2-(4-aminomethyl-3-methylphenyl)5,6
, 7.8-tetrahydro 4H-thiazolo[5.4-b
]Azevin dihydrochloride 2-(4-cyano-3-methylphenyl)-5.6,7
．． 8-Tetrahydro-4H-thiazolo[5,4-b]azepine (20 g) and cobalt chloride hexahydrate (35.3
g) methanol/tetrahydrofuran mixed solution (9
0F! 12/6 0d) was cooled with water, and sodium borohydride powder (33.1 g) was added little by little thereto, followed by stirring at room temperature for 20 hours. The reaction solution was made acidic by adding 4N aqueous hydrochloric acid, extracted with diethyl ether, and the aqueous layer was made alkaline with aqueous ammonia and extracted with chloroform. The extracted layer was dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified with a silica gel column and then neutralized with hydrogen chloride to obtain the title compound (yield 20.1%).

Melting point 246-250° (recrystallized from methanol) I R
(KBr) cm-': 3438, 3210,
2936, 1598, 1523. 1493,14
45, 1372. NMR (d.-DMSO) δ: 1. 63 (2H,
m), 1. 80 (2H, m), 2. 41 (
3H, S), 2. 92 (2H, br.s),
3. 08 (2H, br.s), 4. 03(2
H, br. s), 5. 6(1(2H, br.
s), 7. 51 (IH. d, J=8, 63H
z), 7. 72(2}1, m), 8. 56(
IH, brs). Elemental analysis values: CI, H. N3SCQ
Calculated value as t: C, 52.02; H, 6.11;
N, 12.13. S, 9.26; CQ. 20.4
1. Actual value: C, 51.93: H, 6.34. N
, 11, 74. S, 8.98; Cff, 20.25
．． Example 133 2-(2-pyridyl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azevin dihydrochloride 3-picolinoylamide 7
The title compound was obtained by reacting ε-1-cubic lactam with phosphorus pentasulfide and neutralizing the purified product with hydrogen chloride (yield: 57
．． 4%).

Melting point 181-183° (recrystallized from methanol ethyl ether), I R (KBr)am': 2508, 235
6, 1624, 1532, 1464, 777.
NMR (d8-DMSO) δ: 1. 60-1. 8
9 (48, m), 2. 94 (2tL t, J
= 6Hz), 3. 09-3. 14 (2H, m
), 7. 45-7. 52 (IH, m). 8.
03 (IH, t, J = 8Hz), 8. 14
(IH, d, J= gHz), 8. 56 (IH,
d, J=5Hz). Elemental analysis value: C 12H
Calculated value as I3N3S・2HCC: C, 47.37
．． H, 4.97. N, 13.81; S, 10.
54. Actual sword value: C, 47.28; H, 4.93; N, 1
3.95;S, 10. 32 Example 134: 2-[4-(4-methylbiperanyl)phenyl]5
,6,7.8-tetrahydrogen-4H-thiazolo[5,4
-b] Azevin trihydrochloride By the same method as in Example 1, i[4-(4methylpiperanyl)benzoyl]amino-epsilon prolactam and phosphorus pentasulfide were reacted, and after purification, the raw botanical was chlorinated. Neutralization with hydrogen gave the title compound (yield 17.5%).

Melting point 176-177° (recrystallized from methanol/ethyl ether). I R (KBr)am-': 3410, 269
8, 1601, 1537. 139g, 1251
．． NMR (d.-DMSO) δ: 1. 57-1.
94 (4H, m), 2. 79 (3H, d, J
= 4Hz), 2. 93-2. 99 (2H, m
), 3. 03-4. 11 (10H, m), 7
．． 1D2H, d, J= 9Hz), 7. 89
(2H, d, J = 9Hz). Elemental analysis value: C
, 8H. ．． Calculated value as N 4S・3HCf2・1.5H20: C, 46.51; H, 6.50; N, 1
2.05;S, 6.90. Actual value: C, 46.76; H, 6.48; N, 1
2.25; S, 6.72. Example 135 2-(l-methyl-1.8-1.2.3-triane-1-4-yl)-5.6,7.8-tetrahydro 4H-thiazolo[5.4-b]azevin hydrochloric acid 3-(1-methyl-IH- 1.2.3
- Triazole-4-carbonyl)amino-ε-monolactam was reacted with phosphorus pentasulfide, and the purified product was neutralized with hydrogen chloride to obtain the title compound (yield 45.5%).

Melting point 199-201° (recrystallized from methanol) [
R(KBr)am': 3216, 1610,
1567, 1521. 1495, 1353, 1
232. NMR (d.-DMSO) δ: 1. 55-1. 8
5 (4H, m), 2. 812. 87 (28,
m), 3. 04-3. 11(2}1, m),
4. 12 (3H, s), 9. 61 (IH, s) Elemental analysis value: C,. H, 3N, S - HC (calculated value: C, 44.19; H, 5.19; N, 2
5.77; S, 11.80; Cf2, 13.05. Actual value °C, 44.20. H, 5.12; N, 25.
61;S L1.56;C(!,12.82Example 136 2-(indol-3-yl)-5.6,7.8tetrahydro-4H-thiazolo[5.4-b]azepine/hydrochloric acid 3-(indole-3-
Carponyl)amino-ε-cabrolactam and phosphorus pentasulfide were reacted, and the purified product was neutralized with hydrogen chloride to obtain the title compound (yield 9, 8%).

Melting point 227-229° (recrystallized from methanol/ethyl ether). r R (KBr) cm-': 3134, 160
9, 1495, 1435, 1346, 1241
．． 740 NMR (d-DMSO) δ: 1. 60-1. 8
0 (4H, m). 2. 912. 97 (2H,
m), 3. 00-3. 10 (2H, m), 7
．． 27-7. 32 (2H, m), 7. 56-
7. 61 (IH. m), 7. 79-7. 84
(IH, m), 8. 67 (IH, dJ=3Hz
). Elemental analysis value: C IsH 15N 3S 'HC
(Calculated value as l: C, 58.90; H, 5.27
; N, 13.74S, 10. 48; C (1
．． I1. 59. Actual value: C, 5g. 79;H,
5.14; N, 13.63; S, 10.19; C(
! , 11.32. Example 137 2-(4-chloroo-3-nitrophenyl)-5,6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]acevin The title compound was obtained from 4-chloro-3-nitrobenzoic acid, 3-amino-epsilon-cabrolactam, and phosphorus pentasulfide in the same manner as in Example 18 ( yield 30.7%).

Melting point 116-118° (recrystallized from methanol) I
R(KBr)cm-': 3372, 1562.
1528. 14g4, 1440, H69,13
52, 1339, 1296. 1260NMR(C
DC(3)δ: 1. 71 (28, m). l.
85 (2H, m), 2. 94 (2H, t), 3
．． 15 (2H, t), 4. 09(If{, b
rs), ? ．． 5i(It{,d,J28.47H
z), 7. 86 (IH, dd, J = 2.
17Hz, 8. 47Hz)8. 23 (IH. d
, J22.17Hz) Elemental analysis values: C, 3H, 2N
, SC (calculated value as 20-0.5H20 C, 48.98; H, 4.11; N, 13
．． 18; C c, 11. 12. Actual value: C, 49.35; H, 3.84; N, 1
3.09; C x, +0. 97. Example 138 2-(l-methyl-2-pyrrolyl)-5.6,7.8-
Tetrahydro-4H-thiazolo[5,4-b]azevin hydrochloride In the same manner as in Example 18, -methyl-2-pyrrolecarboxylic acid, 3-amino-epsilon lactam and phosphorus pentasulfide were reacted. After purification, the title compound was obtained by neutralization with hydrogen chloride (yield: 23.1%).

Melting point 193-196° (recrystallized from methanol). I
R (KBr)cm-': 343g, 3204
, 1610, 1528, 14134, 1472
1422, 1363, 1351. 1073NMR
(d8-DMSO-D.0)δ: l.
70(2}1, m)1. ．． 82 (28. m),
2. 88 (2H.t), 3. 11(2H, t
), 3. 88 (3H, s)6. 20 (IH,
m), 6.85 (IH, m), 7. 05 (IH
, m). Elemental analysis values: C, 2H, 6N3S C
l! Calculated value: C, 53.42; H, 5.98
; N, 15.57S, 11.89; CQ, 13.1
4. Actual value: C, 53.55; H, 6.06; N
,+5.72;S,12.00;C(1.12.8B
．． Example 139 2-(1,2-dimethyl-5-penzimidazolyl)-
5.6,7.8-Tetrahydro-4H-thiazolo [5.
4-bl azepine dihydrochloride By the same method as in Example 18, ■,2-dimethylbenzimidazole-5-carboxylic acid, 3-amino-ε monolactam and phosphorus pentasulfide were reacted and purified, and then purified with hydrogen chloride. After neutralization, the title compound was obtained (yield: 13.8%).

Melting point 172-175° (recrystallized from methanol). J
R (KBr) cm-': 3428, 1601
, 1523. 1462, 1439, 1373,
1343, 1251. NMR (dll-DMSO-CDCI2s) δ: 1.
73 (2H, m), 1. 88 (2H, m),
2. 93 (3H, s), 3. 02 (2H. m
), 3. 16 (2H, m), 4. 01(3H
, s), 5. 07 (LH, brs), 7.
98 (2B, t, J= 9.7111z), 8
．． 32 (IH, s) Elemental analysis value: C,. H,
llN, S・2HCf2・2H. Calculated value as 0: C, 47.18; H, 5.94; N, 1
3, 75; S, 7.87; CR, 17.41. Actual measurements: C, 47.40; H, 5.75; N, H. 7
9; S, 8.12; C&, 17.31. Example 140 2-(1-methylimidazol-5-yl)-5,6,
7.8-Tetrahydro-4H-thiazolo[5,4b coazepine dihydrochloride By the same method as in Example 1, 3-(1-methylimidazol-5-ylcarbonyl)amino-ε-monolactam and phosphorus pentasulfide were prepared. After purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield 21.9%).

Melting point 240-243° (recrystallized from meta/-ruethyl ether) I R (KBr) am-': 3080, 256
(1, 1358. 142g, 1233, [09
, NMR (d.-DMSO) δ: 1. 52-1.
83 (4H.m), 2. 84 (2H, t, J
= 6Hz), 3. 00-3. 06 (2H,
m), 4. 04 (3H, s)8. 08(LH,
d, J=2Hz), 9. 27 (IH, br
．． s), elemental analysis value: C,,H,4N4S・2
Hc (calculated value: C, 43.00; H, 5.2
5. N, 18.24:S, 10. 44. Actual value: C, 42.73; H, 5.40; N, 1
8.08;S, 10. 09, Example 141 2-(1-methylimidazol-4-yl)-5,6.
7.8-tetrahydride-4H-thiazolo[5,4b coazepine dihydrochloride 3-(1-methylimidazol-4-ylcarbonyl)amino-ε-caprolactam and phosphorus pentasulfide were prepared in the same manner as in Example 1. After reaction and purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield 12.4%).

Melting point 179-180' (recrystallized from methanol-ethyl ether). I R (KBr) cm-': 3446, 302
6, 2596, 2370, 1475, 1438
, l298 NMR (d=-DMSO) δ: l. 55-1. 8
2(4}1, m), 2. 85 (2H, t, J
= 6Hz). 3. 04(2H, t, J =
5Hz), 3. 84 (3H, s), 8. 15
(IH, s), 8. 86 (IH, s). Elemental analysis value: C. ,H,. Calculated value as N4S-2H CN: C, 43.00; H, 5.25; N
, 1g. 24;S 10.44. Actual value: C, 42.67; H, 5.44; N, 1
8.04;S. 10. 42. Example 142 2-(3-amino-4-chlorophenyl)-5,6,7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azevin dihydrochloride 2-(4-chloro-3-nitrophenyl)-5+6.7
．． 8-Tetrahydro-4H-thiazolo[5.4b]azepine (4.3g, 13.9mM) was dissolved in a mixed solvent of acetic acid (40d) and water (10d), iron (4.3g) was added, and the mixture was heated at 90°C. The mixture was heated and stirred for 30 minutes. After removing iron, the reaction solution was concentrated and the resulting residue was purified using a silica gel column. This was neutralized with hydrogen chloride to obtain the title compound (yield 28.8%).

Melting point 195-197° (recrystallized from methanol), T
R (KBr)cm-': 3430, 321g
, 1603, 1521, 1489, 1437,
1373, 1329, 1251, 1053. N.M.
R(d.-DMS○)δ: l. 69 (2H, m)
, 1. 82 (2H, m), 2. 92 (2H,
t, J = 5. 3Hz). 3. 11 (2H
, t, J-5. 0Hz), 5. 01(2H,
br. s), 7. 13 (IH. dd, J =
2. 1Hz, 8. 4Hz), 7. 29 (IH
, d, J=8. 4Hz), 7. 34 (IH
, d, J=2. 1Hz). Elemental analysis value: C
．． ．． H. @N. S C Q3・0. Calculated value as 5H, ○: C, 47.86; H, 5.25; N, 1
2.8g. Actual value: C, 48.00. H, 4.74
; N, 12.81 Example 143 2-(4-cyano-3-ethylphenyl)-5+6.7
．． 8-Tetrahydro-4H-thiazolo[5,4b]azebin The title compound was obtained from 4-cyano-3-ethylbenzoic acid, 3-amino-epsilon-lactam and phosphorus pentasulfide in a manner similar to Example 18. (yield 69.7%).

Melting point 103-105° (recrystallized from ethyl acetate, hexane). I R (KBr)Cm-': 3248. 221
6, 1603, 1536, 1497, 1449
, 1372, 1359, 1306. NMR (c D C(!3)δ: 1.33(3H
, t, J=7. 6Hz), 1. 70 (2H
, m), 1.84 (2H, m), 2.89 (2}1, q
, J= 7.6Hz), 2.96(2H, t, J
= 5. 8Hz), 3. 15 (28. t, J
= 5. 1Hz), 4. 10 (1H, br.
s), 7. 59 (2H, m), 7. 75(
IH, S). Elemental analysis value: C. ,H ,,N 3
Calculated value as S: C, 67, 81; H, 6.05;
N, 14.83; S, 11. 31. Actual value: C, 67.78; H, 6.15; N, 1
4.80;S, 11. 22 Example 144 2-(4-aminomethyl-3-ethylphenyl) 5.6
,7.8-tetrahydro-4H-thiazolo[5.4-b
]Azepine dihydrochloride 2-(4cyano 3
-ethylphenyl)-5.6.7.8-tetrahydride-
The title compound was obtained from 4H-thiazolo[5.4-b]azevin, cobalt chloride hexahydrate and sodium borohydride (yield 12.5%).

Melting point 235-238° (recrystallized from methanol). I
R (KBr) cm-': 2848, 1596
．． 1520, 1451, 1439, 1374.
1348 N M R (da D M SO ) δ; 1.
21 (3H, t, J・7.5Hz), 1, 64
(2H.m), 1. 78 (2H, m), 2.
73 (2H, q, J= 7.5Hz), 2.
9 1 (2H, m), 3. 06 (21 m),
4. 05 (2H, d, J= 5.4Hz), 4
．． 67 (2H, br.s), 7. 52 (IH
, d, J = 8. 1Hz), 7. 68 (I
H, dd, J= 1. 8Hz, 8. 1Hz).
7. 72 (IH, d, J= 1.8Hz)8
．． 53 (IH, br. s) Elemental analysis value: C, 8H,, N3S・28C (calculated value C, 53.33; H, 6.43・N, 11.6
6 Actual measurement value: C, 53. Ht; H, 6.46; N,
11.51. Example 145 2-(5-methyl-2-chenyl)-5.6.7.8-
Tetrahydride-4H-thiazolo[5.4-b]azevin hydrochloride After reaction and purification of 5-methyl 2-thiophenecarboxylic acid, 3-amino-ε~cabrolactam and phosphorus pentasulfide in the same manner as in Example 18. After neutralization with hydrogen chloride, the title compound was obtained (yield: 334%).

Melting point 148-150' (recrystallized from methanol), I
R(KBr)am-': 3448. 3216
, 1602, 1544, 1520. 1447+
376. 1354, 1279. N M R (d e D M SO ) δ River,
60 (2H, m), 1. 79 (2H, m),
2. 46<3H, s), 2. 81 (2H, t
, J = 5. 27Hz), 3. 05(2f{
, t, J=5. 42Hz), 5. 13 (IH
, br. s), 6. 82 (IH, dd, J
=1. 14Hz, 3. 66Hz), 7. 31
(LH, d, J= 3.66Hz). Elemental analysis value: C ItH I4N ts t ” H C Calculated value as Q: C, 50.25; H, 5.27; N
, 9.77 Actual value: C, 50.20; H, 5.27
・N, 9. 79. Example 146 2-(1,3-dimethylvirazol-4-yl)-5.
6,7.8-tetrahydride-4H~thiazolo[5.4-
b] Azepine hydrochloride By the same method as in Example 1, 3-(1,3-dimethylpyrazol-4-ylcarponyl)amino epsilon monocab lactam and phosphorus pentasulfide were reacted, and the purified product was chlorinated. Neutralization with hydrogen gave the title compound (yield 17.1%).

Melting point 2 15.0-2 17.0° (recrystallized from methanol-ethyl ether). I R (KBr)am"-': 320g, 27
54, 1612, 1519, 1438, 131
1NMR (d. 1DMS○) δ: 1. 55-1.
82 (4H, m). 2. a5 (3H, s),
2.88(2}1, t, J = 5[1z),
3. 05 (2H, t, J-5Hz)3. 83(
3H, s), 8. 51 (IH, s). Elemental analysis value: Calculated value as CI2HI6N4S-HCl2: C
, 50.61; H, 6.02; N, 19.67; S
, 11, 26・C &, 12. 45. Actual value: C,
50, 47; H, 6.14; N, 19.71:S
, 11. 14; C c, 12. 76. Example 1 4. 7 2-(1,3-dimethylpyrazol-5-yl)-5.
6,7.8-Tetrahydro-4H-thiazolo[54-b
]Azepine hydrochloride By the same method as in Example 1, 3-(1,3-dimethylvirazol-5-ylcarbonyl)amino e-cabrolactam and phosphorus pentasulfide were reacted, and after purification, the raw product was treated with hydrogen chloride. Neutralization gave the title compound (yield 40.1%).

Melting point 273.0-275.00 (recrystallized from methanol-ether). I R (KBr)c+n': 3200, 16
06, 1467, 1441, 1355, 126
9. NMR (d.-DMSO) δ: l. 54-1.
83 (4H, m), 2. 15 (3H, s),
2. 83 (2B, t, .+ = 6Hz), 3
．． 02 (2H, t, J=5Hz)4. 01(
3H, s). 6. 34 (IH, s). Elemental analysis values: C,,H,. N. Calculated value as S-H CI2: C, 50.61; H, 6.02; N, 1
9.67;S, 11. 26. Actual value: C, 50.39. H, 6.03: N, 1
9.65;S, 11. 66 Example 148 2-[2-(3-indolyl)ethenyl]-5.6,7
, 8-Tetrahydro-4H-thiazolo[5.4-b]azepine dihydrochloride 3-(3-indolylacryloyl)amino~ε-cabrolactam and phosphorus pentasulfide were reacted in the same manner as in Example 1. After purification, the product was neutralized with hydrogen chloride to obtain the title compound (yield: 49.5%).

Melting point 235.0-237.0' (recrystallized from methanol-ethyl ether). I R (KBr)am-': 1614, 157
5, 1501, 1434, 1239. 938N
MR (d.-DMSO) δ: 1. 69 (4H, b
r. s), 2, 80-2. 86 (2B, n+)
, 3. 05-3. 12 (2H, n+), 7.
16-7. 28(2}1, m)7.38(IH,
d, J = 16Hz), 7. 44-7. 5
3 (IH, m), 7. 83(1[1,d, J
= 1611z), 7. 91 (IH, d, J
= 3Hz), 7. 94-7. 99 (IH, m) Elemental analysis value C, 7H. ,N3S-2HC
Calculated value as C: C, 55.44; H, 5.20:
N, 11.41; S, 8.71 Actual value: C, 55.40; H, 5.40. N,1
1.22; 3 8.55 Example 1 4. 9 2-(1.5-dimethylpyrazol-3-yl)5.6
,7.8-tetrahydro-4H-thiazolo[54-b]
Asepino hydrochloride By the same method as in Example 1, 3(1.5-7methylpyrazol-3-ylcarbonyl)amino epsilon-cabrolactam and phosphorus pentasulfide were reacted, and after purification, the product was neutralized with hydrogen chloride. The title compound was obtained (yield 25.3%).

Melting point 207.0-208.0' (methanol-ethyl ether or S recrystallization) + R (KBr) cm': 31g8, 293
4, 1604, 1556, 1354. 1241
11NMR (d.-DMS○) δ: 1. 55-1.
82 (4H, m). 2. 30 (3H, s),
2. 83-2. 90 (2H, m), 3. 0
5 (2H, t, J = 5Hz), 3. 78(3
H. s), 6. 78 (IH.s). Elemental analysis value: C 1tH +-N-S'H CQ・0.3H
Calculated value as tO: C, 49.66; H, 6.11; N, 1
9.31S L1.05; Cf2, 12.22 actual value: C, 49.68; H, 6.20; N, 19.
28S, 10. 97. C Q. 11. 92
．． Example 150 1-(5.7-dimethylpyrazolo[1.5-a cobyrimidin-3-yl)-5.6,7.8-tetrahydro 4H
-thiazolo[5.4-b]azepine dihydrochloride Example 1
By the same method as above, 3-(5.71-methylvirazolo[1.5-a]pyrimicin-3-ylcarbonyl)amino-epsilon-lactam and phosphorus pentasulfide were reacted, and after purification, the product was neutralized with hydrogen chloride. The title compound was obtained (yield: 2
8.3%).

Melting point: 249.0-252.0° (recrystallized from methanol-ethyl ether). I R (KBr) cm': 2622, 162
1, 1572. 1543, 1442. 1237
NMR(d,-DMS○)δ: l. 73 (4H,
br. s), 2. 64 (3H, s), 2.
76 (3H, s), 2. 87-2. 92(2)
H, m), a, 05-3. 11 (2H, m)
, 7. 20 (IH, s), 9. 03(LH,
s). Elemental analysis values: C, 5H, 7N. S・2HC
Calculated value as Q: C, 4839. H, 5.14;
N, 1g. 81;S, 8.61. Actual value: C, 48.06; H, 5.05; N, 1
8.58:S874 Example 151 2-(2-biphenylyl)-5.6,7.8-tetrahydro 4H-thiazolo[5,4-b]acepine Example 1
3-(2-biphenylylcarbonyl)amino-ε-cabrolactam and phosphorus pentasulfide were reacted in the same manner as above to obtain the title compound (yield 10.3%).

Melting point 14 1.0-142.0' (recrystallized from cyclohexane) I R (KBr) cm': 3222, 293
4, 1533. 14g4, 1372. 7496
98. NMR (CDCC3) δ: I. 58-1. 82(
4H, m), 2. 87-2. 93 (2H, m
), 2. 96-3. 02 (21+, m), 7
．． 23-7. 44 (8H.m), 7.98-8
．． 04 (18, m) Elemental analysis value: C,. H. Calculated value as N2S
C, 74.47; H, 5.92. N, 9.14. S
, 10. 46. Actual value: C, 74.75; H, 6.01; N, 8
．． 92;3 10.15 Example 152 1-[2-(1-methylimitazol-5-yl)ethenyl]-5.6,7.8-tetrahydro-4Hthiazolo[5.4-b]acepine・Dihydrochloride 3-(1-methylimidazol-5-ylacryloyl)aminoε-cabrolactam and phosphorus pentasulfide were reacted in the same manner as in Example 1, and after purification, the raw product was neutralized with hydrogen chloride. The title compound was obtained (yield 6.3%).

Melting point 249.0-250.0' (recrystallized from methanol). I R (KBr)am-': 2726, 159
6, 1501, 1372, 1349. 1251
NMR (d.-DMS○)δ: ]. 53-1. 7
7 (4H.m), 2. 782.86 (2H, m)
．． 2.98-3. f) 5 (2L m'). 3.89 (3
}1, s). 7.10 (IH, d, J= 16.
2Hz), 7. 32 (IH. d, J = 16
．． 2Hz), 8. 06 (IH, s), 9.
08 (IH, s). Elemental analysis value: C,. H. a
N. Calculated as S 2 H Cl2: C, 46.
85. H, 5.44. N, 16.81. S9.
62; CC, 21.27 Actual subvalue: C, 46.61; H, 5.50; N, 1
6.52; 8 9.33; CQ. ．． 21.2B. Example 153 2-[2-(henzimidazol-5-yl)ethenyl]-5.6.7.8-tetrahydro-4H-thiazolo[
5,4-b]Azepine dihydrochloride In the same manner as in Example 18, 5-penzimitazolyl acrylic acid, 3-amino-epsilon lactam, and phosphorus pentasulfide were reacted, and after purification, the raw botanical was neutralized with hydrogen chloride to obtain the title compound (yield 33.5%).

Melting point 250.0-25 1.0' (recrystallized from methanol ethyl ether). J R (KBr) cm': 2994, 293
2, 1606, 1527, 1354. 955.
NMR (d.-DMSO) δ: I. 53-1. 7
7 (4H, m), 2,782. 84 (2H, m
), 2. 98-3. 05 (2H, m), 7.
45 (IH, d, J-16. OHz). 7
．． 60 (IH, d, J = 16.0Hz),
7. 86 (2H, s), 803 (IH, s)
, 9. 64 (LH, s) Elemental analysis value: C,.
H, 8N. Calculated value as S・2HCC・1.5H,O: C, 48.49. H, 5.43; N, 1
4.14; S, 109; C (, 17.89. Actual value: C, 48.9+.; H, 5.3 g. N,
14.18. S, 7.93; Cf2, 17.6
1. Example 154 2-+3-(2,7-dimethylimidazoN.2-a]
pyridyl) 1-5.6,7.8-tetradraw 4 Hthiazolo[5.4-b]acepine dihydrochloride 2,7-dimethylimidazo[1.21a]pyridine-3-carboxylic acid (7 1,1'-carbonylsiimidazole (7.3 g, 45 mmol) was added to a dimethylformamide solution (30 d) of .8 g, 41 mmol) and heated under reflux for 30 minutes. In this reaction limb, 3-amino-epsilon lactam (
5.8 g, 45 mmol) was added thereto and heated under reflux for 2 hours. After cooling to room temperature, add sodium bicarbonate solution and extract with a mixture of C70 form and methanol. After drying with magnesium sulfate,
The solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography, and the resulting powder was treated with phosphorus pentasulfide (10 g,
45 mmol) in pyridine (80d), and the mixture was heated and stirred at IO O'C for 44 hours. After cooling to room temperature, aqueous sodium bicarbonate was added and extraction was performed with a mixed solvent of chloroform and methanol. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography, neutralized with hydrogen chloride, and then recrystallized from methanol to obtain 3.73 g (24.5%) of the title compound.

Melting point: 154-157° (recrystallized from methanol). I
R (KBr) cm': 3452, 1659
, +604. 1571, 1527, 1456,
1390, +362. 1305, +258. N~
ffR(d.-DMso)δ: I. 86 (21 m
), 1. 78 (2H, m)2. 57 (3H,
s), 2. 66 (3H, s), 2. 93(2)
H, m), 3. 17 (2H, m), 4. 07
(18, br. s), 7. 44 (IH. dd
, J = 1. 65Hz, 6. 96Hz).
7. 79 (IH. d, J= l. 65Hz),
9. 65(II{, d, J= 6.96Hz
) Elemental analysis values: C, sH, sN 4S・2HCff
・Calculated value as 0,8H,O: C, 49.82; H, 5.64; N, 1
4.52;S, 8.31;CQ. , 18.3g
．． Actual value: C, 50.01; H, 5.80. N,
14.32. S, 8.38; C(!, 18.2
0 Example 155 2-{4-(4-methylimidazol-1-yl)styryl-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azevin dihydrochloride Example 4-(4-methylimidazole-1-
The title compound was obtained by reaction and purification of cinnamic acid, 3-amino-ε-1-cab lactam, and phosphorus pentasulfide, and then neutralized with hydrogen chloride (yield: 34.1%).

Melting point: 239-241° (recrystallized from methanol). I
R (KBr) cm-': 3440, 1626
, 1595, 1547, 1505, 14421
371, 1352, 1302, 964. NMR (
d. -DMs○)δ: 1. 58-1. 83 (41
{, m), 2. 38 (38, s), 2. 8
3 (2H, m). 3. 07 (2H, m), 7
．． 40 (2H, s), 780 (2tl, d.
J=8. 83Hz), 7. 88 (2H, d
, J = 8. 83Hz), 8.02(IH.
s), 9. 63 (IH, s). Elemental analysis value: C,
．． H. Calculated value as N4S・2HCQ・0.5820: C, 54.54; H, 5.54; N, 1
3.39; S, 7.66; Cf2, 16.95
．． Actual value: C, 54.62; H, 5.55; N,
13.62S, 7.65; Cf2, 17.08
Example 156 2i3-(6-chloro-2-methylimidazo[12-a
]pyridyl)l-5.6,7.8-4H-thiazolo[5
．． 4-b]Azepine dihydrochloride By the same method as in Example 154, 6-chloro2-methylimitazo[1.2-a]pyridine-3carphonic acid, 3
-Amino-ε monocapsulactam and phosphorus pentasulfide were reacted and purified, and then neutralized with hydrogen chloride to obtain the title compound (yield 16
．． 7%).

Melting point: 233-236° (recrystallized from methanol). I
R (KBr)cm': 3424, 1549
, 1514. 1488, 1436, +395,
1348, 1255. NMR (d.-DMSO) δ: 1. 67 (2H,
m), 1. 77(21{, m), 2. 94(
2H, m), 3. 06 (2H, m), 5.
94 (IH, br. s), 8. 03(2H,
s), 9. 9: {(IH.s) Elemental analysis value: C1
Calculated value as 5H1,N4SCQ・2HCQ・0.5H20: C, 44.96; H, 4.53; N, 1
3.98;s, g. oo. Actual value: C, 44.58; H, 4.75; N, 1
3.63;S, 7.80. Example 157 2-(2-imitazo[1.2-a]pyridyl)-56.
7.8-Tetrahydro-4H-thiazolo[5,4b]azepine dihydrochloride Imidazo[1,2-
After reaction and purification of alpyridine-2-carboxylic acid, 3-amino epsilon-cabrolactam and phosphorus pentasulfide, the title compound was obtained (yield: 17.2%) by neutralizing with hydrogen chloride.

Melting point 176-179° (recrystallized from methanol) I
R(KBr)am': 3488, 3030.
1572, 1529, 1450. 1432.1
367 1204 NMR (d.-DMSO) δ: 1. 68 (2H,
m), 1. 78 (2H, m), 2. 91(2)
H, t, J=5. 13Hz), 3. 09(
21, t, J = 4. 72Hz), 7. 46
(IH, m), 7. 86 (2H, m), 8.
77 (IH, s), 8. 89 (IH, d, J
= 6. 72Hz) Elemental analysis value: C. ,H,. N,S-2H
Calculated value as Ci2: C, 48.98; H, 4.7
0; N, 16.32; S, 9.34. Actual value: C, 48.55; H, 4, 84; N, 1
6.07;S, 9.30. Example 158 2-(6-chloroimitazo[1.2-a]pyridine 3-
yl)-5.6.7.8-tetrahydride-4HthiazoloC5,4-bE azepine hydrochloride By the same method as in Example 154, 6-chloroimitazoCI,2-a3pyridine-3-carboxylic acid, The title compound was obtained by reaction and purification of 3-amino-ε-monolactam and phosphorus pentasulfide and neutralization with hydrogen chloride (yield: 16.0%).

Melting point 245-248° (recrystallized from methanol). I
R(KBr)am': 3420, 1553
, 1510, 1475, 1430. 1386,
1342. NMR (d.-DMSO) δ: 1. 65 (2H,
m), 1. 76 (2H, m)2. 91 (2H,
t, J=5. 13Hz), 3. 04 (2H
．． m), 4. 31 (IH, br. s). 7.
92 (LH, dd, J= 1.93Hz, 8
．． 1ll7Hz), 8. 03 (18, d, J
= 8. 87Hz), 8. 59 (IH, s),
9.84 (IH, d. J= 1.93Hz). Elemental analysis value: C14H13N4SCQ-HC (calculated value as 2: C, 49.27: H, 4.13. N, 1
6.42. S, 9.39; Cff. 20.7g. Actual value: C, 49.23; H. 4.11; N, 16
．． 38; S, 9.25; (12.20.49. Example 159 2-(8-imidazo[1.2-a]pyridyl)-5,6
．． 7.8-tetrado-4H-thiazolo[5.4b]azepine dihydrochloride imidazo[1.2-a]pyridine-6-carboxylic acid hydrobromide salt (9.34 g, 38.6 mmol) Tetrahydrofuran (30d!) and triethylamine (7.
8 1 g, 7 7.2 mmol) and 1,1'-carbonyldiimitazole (6.88 g, 42.4 mmol)
was added and heated under reflux for 30 minutes. Add 3-amino-ε-caprolactam (5.4 4 g, 4 2.4
mmol) was added, heated under reflux for 30 minutes, and further stirred at room temperature for 2 days. Aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with a mixed solvent of chloroform and methanol. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography, and the resulting powder was purified with phosphorus pentasulfide (5
．． 44 g, 424 mmol) with pirin (50 d)
The suspension was heated and stirred at 120-130°C for 5 hours. After cooling to room temperature, diluted bodice water was added and extracted with a mixed solvent of chloroform and methanol. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified on a silica gel column, neutralized with hydrogen chloride, and recrystallized from methanol to yield 76.1 mg (0.6%) of the title compound.
Obtained.

Melting point: 189-192° (recrystallized from methanol). I
R(KBr)Cm-': 3450, 1642
, +572. 1520. 1506, 1461,
13g5,1373,1330. NMR (d.-DMS○) δ: 1. 66 (2H,
m), 1. 77 (2H, m), 3. 06 (4H
, m), 4. 64 (IH.br.s), 7
．． 52 (IH, t+J-=711Hz), 8
．． 08 (LH, d, J = 7.41Hz),
8. 15 (LH, d, J = 2.02Hz),
8. 52 (IH, d, J = 2.02Hz),
8. 89 (LH, d, J = 663HZ) Elemental analysis value: c 1-H 14N-S・2HCf2・
H. Calculated value as 0: C, 46.54; H, 5.02: N, 1
5-51;S, 19. 63. Actual value: C, 46.80: H, 4.73; N, 15
．． 78;S, 19. 49. Example 160 2i3-(2-methylimidazo[1.2-a cobiridyl)l-5.6,7.8-tetrado-4H-thiazolo[5.4-b]azepine dihydrochloride Example 18 By a similar method, 2-methylimidazo [1. , 2-a] pyridine-3-carboxylic acid, 3-amino-ε-cabrolactam, and phosphorous pentasulfide were reacted and purified, and then neutralized with hydrogen chloride to obtain the title compound (yield 5.7%).

Melting point 219-221° (recrystallized from methanol), r
R (KBr) cm-': 33g0, 1605
, 1523, 1483, 1449. 140g,
1352, 1322, 1264. NMR (d.-DMSO) δ: 1, 66 (2H,
m), 1. 71 (2H, m)2. 72 (3H,
s), 2. 94 (2H.m), 3. 07(
2H, m), 5. 00(IHbr.s), 7
．． 58 (IL m), 8. 01 (2H, m),
9. 83 (IH, m). Elemental analysis value: C, s
Calculated value as H,aN4S・2HCl2: C,50
．． 42; H, 5.08; N, 15.68; S, 8
．． 91: CI2, 19.84. Actual value: C, 49.9
8; H, 5.20; N, 15, 59; S, 8.9
4: C (1.19.64. Example 161 2-(4-cyano 3-isobrobylphenyl) 5,6
．． 7.8-Tetrahydro 4H-thiazolo[54-b]
The title compound was obtained from 4-cyano-3-isobrobylbenzoic acid, 3-amino-epsilon-cab-lactam, and phosphorus pentasulfide in the same manner as in Azepine Example 18 (yield: 62.0%).
).

Melting point l25-127° (recrystallized from ethyl acetate, hexane). I R (KBr)am-': 3220, 221
6, 1603, 1553, 1520, 1497
, 1437, 1369, 1354, 1266. N
M R (C D Cl!3) δ: 1. 36 (6
H, d, J=6. 92Hz), 1. 70 (2
H, i), 1, 85 (2H, m), 2. 96
(2H, t, J=s. 74Hz), 3. 14
(2H, t, J= 5.17Hz). 3. 3
8 (IH, m). 4. 09 (IH.br.s)
, 7.58 (2H, s), 7. 80 (IH,
s). Elemental analysis value: C. Calculated value as 7H, IIN3S: C, 68.65. H, 6.44; N, 1
4.13;S, 10. 7g. Actual value: C, 68.50: H, 6.72. N,1
4.25;S, 10. 61. Example 162 2-(4-aminomethyl-3-isoprobylphenyl)
-5.6,7.8-tetrahydro-4H-thiazolo[5
．． 4-b]Azepine dihydrochloride 2-(4-cyano-3-imbrobylphenyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4 -b] The title compound was obtained from acepine, cobalt chloride hexahydrate and sodium borohydride (yield 351%).

Melting point 260-263° (recrystallized from methanol) I
R(KBr)am-': 3450, 2932,
1599, 1520, 1463, 1371.1
353 NMR (de-DMSO) δ: 1. 25 (68,
d, J=6. 80Hz), 1. 63 (2H,
m), 1. 77 (2H, m). 2. 92(2)
H. t, J = 5. 27Hz), 3. 06(
2H, t, J= 4.85Hz), 3. 19(
LH, m), 4. 14 (3H, br.s).
7. 52 (IH. d, J = 8. lOHz),
7. 64 (IH, dd, J= 1.83Hz
．． 8. 10Hz), 7. 86(1) {. d,
J = 1. 83Hz), 8. 54 (2H,
br. s). Elemental analysis value: C, 7H, 3N3S・2HCR・0
．． Calculated value as DH20: C, 53.26; H, 6.84. N,1
0.96; S, 8.36; Cff, 18.49 Actual value: C, 53.54; H. 6.38; N, 10.
92S, 8.20. CI2.18.48. Example 1
63 2-{4-(imitazol-1-yl)phenyl}-5
．． 6,7.8-tetrahydro 4H-thiazolo[5,l
-b] Acevin dihydrochloride 4-(imitazol-l-yl)benzoic acid, 3-amino-epsilon lactam and phosphorus pentasulfide were reacted and purified in the same manner as in Example 18, and then neutralized with hydrogen chloride. The title compound was obtained (yield 619%).

Melting point 229-231' (recrystallized from methanol) I
R(KBr)am-': 2636. 1616.
1597, 1540, 1475, 1453,1
374, 1352, 1336. NMR (d, -DMS○) δ: I. 66 (2H,
m), 1. 81 (2H, m), 2. 92(2)
H. m), 3. 06 (2H, m), 5. 0
0 (IH, br. s), 7. 97 (5H, m
), 8. 39 (IH, s), 9. 89(1}
1, s) Elemental analysis value・C,. H. 6N, S・2HC&
Calculated value: C, 52.04; H. 4.91;
N, 15.17; S, 8.68; CQ, 19.20
．． Actual value: C, 51.63; H, 4.89; N,
14.90; S, 8.49; Cf2, 18.81.
Example 164 2-(2.2-cyphenylethenyl)-5.6.78-
Tetrahydro 4H-thiazolo[5.4-b]azepine 3,3-diphenyl-
The title compound was obtained from 2-bropenic acid, 3-amino-ε-cafrolactam and phosphorus pentasulfide (yield 75.6%).
.

Melting point 169-171° (recrystallized from ethyl acetate) I
R (KBr)cm': 3290, 1599,
1549. 14g7, 1441, 1435,1
415, 1369, 1349, 1254. NMR
(CDC(..-D20)δ: 1.61(2H,
m), 1. 73 (2H, m). 2. 83 (2
H, t, J=5. 64Hz), 2. 94(
2H, t, J4. 95Hz), 7. 20 ~
7. 37 (8H, m), 7. 43 ~7. 5
4 (3H, m). Elemental analysis values: C,,H,oN
Calculated value as 2S: C, 75.1117; l{,
6.06; N, 8.43S 9.64. Actual value: C, 75.77; H 6.12; N, 8
J5;S, 9.51. Example 165 2-+2-(1-methylimitazol-4-yl)ethenyl l-5.6,7.8-tetrahydro-4 I-{thiazo[5.4-b]acepine dihydrochloride 3-{β-(
1-methylimitazol-4-yl)acryloyl}amino-ε-cabrolactam (826 g, 0.32 mol)
, phosphorus pentasulfide (70 g, 0.32 mol) was dissolved in pyridine (30
0d) at 120'C for 8 hours and then at 70'C for 1
The mixture was heated and stirred for 4 hours. After cooling to room temperature, add aqueous sodium bicarbonate to the reaction mixture and extract with a mixed solvent of chloroform and methanol.
The mixture was dried with magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography, neutralized with hydrogen chloride, and then recrystallized from methanol to obtain 18.9 g (78.2%) of the title compound.

Melting point 193-196° (recrystallized from methanol) I
R (KBr)cm': 3418, 2992,
1636, 1599. 1513, 144914
37. +374. 1360, 1273, 125
1,944 NMR (d8-DMSo) δ: I. 6
3 (2H, m), 1. 74 (2tl, m),
2. 83 (2H, m), 3. 05 (2H, m
), 3. 87 (3H, s), 4. 95 (IH
,br. s), 7. 16(IH, d, J=
16. 31Hz), 7. 47 (IH, d, J
16. 31Hz). 7. 86 (LH, s),
9. 19 (IH, s). Elemental analysis value: C,. H
、． Calculated value as N, S・2 HC Q・0.5820: C, 45.62; H, 5.59; N, 1
6.37S, 9.37: Cf! , 20.71 Actual value: C, 45.66; H, 5, 53; N, 16
．． 50;S, 9.63. CR, 20.86 Example 166 2-11(1-ethylimitazol-4-yl)ethenyl-5.6,7.8-tetrahydro-4Hthiazolo[
5,4. -b]Azepine dihydrochloride By the same method as in Example 165, 3-{β-(lethylimidazole-4
-yl)acryloyl}ami/1epsilon-cabrolactam and phosphorus pentasulfide were reacted and purified, and then neutralized with hydrogen chloride to obtain the title compound (yield: 60.9%).

Melting point: 181-184° (recrystallized from ethanol). l
R(KBr)am': 3430, 1637
, 1600, 1542, 1507, 14511
430, 1374, 1357, 1278. 12
53, 959 NMR (d,.-DMS○) δ: I.
44 (3H, t, J = 7.29Hz11.
62 (211, m), ]. 74 (211, m)
, 2. 82 (2H, m). 3. 05 (2H,
m)4. 21 (2H, q, J = 7.29
Hz), 6. 10 (IH.br.s), 7.
12 (IH. d, J = 16.4Hz),
7. 47 (IH, d, J = 16.4Hz)
, 7. 96 (IH, s), 9. 25 (IH,
s) Elemental analysis value: CI4H 20N-S CI2
Calculated value as 2: C, 48.42: H, 5.80;
N, 16.13; S, 9.23; C&, 20.42
．． Actual value 2G, 4g. 22. H, 5.85: N, 15
．． 91S, 9.31; C (, 19.77. Example 1
67 2-(2-quinolyl)-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azebin 3-(2-ky/lyl)carponylamino The title compound was obtained from the ε-1-cubic lactam and phosphorus pentasulfide (yield 726%).

Melting point 243-245° (recrystallized from ethanol) I
R (KBr)cm': 3254, 1596,
1526, 1502, 1476, 1456,1
434. 1424, 1372, 1356 129
9. NMR (d.-DMS○) δ: I. 69 (4B
, m), 2. 87 (2H, m), 3. 05
(2H, m), 6. 61 (LH, s), 7.
55 (IH, dt, J = 1.32Hz,
6. 81Hz), 7. 74(Ill, dt,
J=1. 32Hz, 6. 81Hz), 794
(2H, br. d. J = 8. 14Hz),
8. 09 (IH, d, J-8.731]z)
,8. 34 (IH. d, J = 8.73Hz)
．． Elemental analysis value: C,. Calculated values as H, 5N 3S: C, 68.30; H, 5.37; N, 14.
93; S, If. 40. Actual value 2C, 68.31; H, 5.39; N, 14
．． 73;S IIJI. Example 168 2-(indazol-3-yl)-5.6.7.8tetrahydride-48-thiazolo[5.4-b]azepine By removal in the same manner as in Example 18, indazole 3-calphone The title compound was obtained from acid, 3-amino-ε-monocaplactam and phosphorus pentasulfide (24% yield).

Melting point 252-255° (recrystallized from ethyl acetate). I
R(KBr)Cm': 3330, 1640
, 1616, 1525. 1495, 1429.
135g, 1338, 1324, 1296, 1
277. NMR (d.-DMSO-D20) δ: I.
77 (4H, m), 300 (2tl, br.
s), 3. 28 (2H.br.s), 7.
46 (IO, t, J-7.65Hz), 7.
65 (IH, t, J = 7.51Hz),
7. 94 (IH, d, J = 8.43Hz)
．． 8. 98 (IH, d, J= 7.43Hz
) Elemental analysis value: C,. H. ．． N. S-0.2H.
Calculated value as O: C, 61.38; H, 5.30;
N, 20.45; S, 11. 70. Actual value C, 61.40. H, 5.18; N, 20
．． 30; S, 11, 70. Example 169 2-+(Z)-4-diethylaminostyryl}-5,6
,7.8-tetrahydro-4H-thiazolo[5,4b]
Azepine 2-{(E)-4-diethylaminostyryl}-5,6
,7.8-tetrahydro-4H-thiazolo[5,4b]
Azepine (1.8g) dissolved in ethanol (200g)
0d) was allowed to stand indoors under scattered light to allow the isomerization reaction to proceed. The title compound was obtained by concentrating the reaction solution and purifying the residue using silica gel column chromatography.
0 mg (41.4%) was obtained.

Melting point 88-91' I R (KBr)am-': 32g0, 160
9, 1539, 1520, 1491, 1435
,1399, 1365, 1352, 1266,
1191. 1154NMR (CDCff3) δ: l
．． 18 (6H, t, J= 7.1Hz), 1
．． 66 (2H, m), 1. 81 (2H, m)
．． 2. 87 (2H, m). 3. 02 (2H,
a+), 3.38 (4H, q, J = 7.
1Hz), 6. 45 (IH, d, J= 12.
0Hz), 6. 59 (IH, d, J= 12
．． 0Hz). 6. 65 (2H, d, J= 8
．． 7Hz), 7. 35 (2H, d, J =
8. 7Hz). Elemental analysis value: C,. H. 5N.
Calculated value as S: C, 69, 68; H, 7.69;
N, 12.83; S, 9.79 Actual value C, 69.10; H, 7.75; N,! 2
．． 49;S,9.62 Example l70 2-f(Z)-4-chlorostyryl l-5.6,7.
8-Tetrahydro-4H-thiazolo[5.4-b]azevin By a method similar to Example 169, 2-+(E)4-chlorostyryl-5.6,7.8-tetrahydride-4H
The title compound was obtained from -thiazolo[5.4-b]azepine (yield 11.2%).

Melting point 128-130'C I R (KBr)am-': 3236, 162
2, 1549, 1521, 1489, 1436
,1367,1355,1273,1250,961,
802NMR(CD(d!3)δ: 1.62(2
H, m), 1. 77(2}1, m), 2.8
5 (2H, t, J = 5.8Hz), 3.
01 (2H, m), 3. 84 (18, br.
s), 6. 60 (1B. d, J= 12. 2H
z), 6. 67 (18, d, J= 12.2
Hz), 7. 35 (4H, s). Elemental analysis value: C +sH +sNzS Calculated value as CQ: C, 61.95; H, 5.20; N, 9.
63;S, 11. oa; C Q. 12. 1
9. Actual value: C, 61.79; H, 5.25; N
, 9.60; s, H. oo; C(2,12.26 Example 171 2-+(Z)-3.4-dichlorostyryl l-5.67
,8-tetrahydro-4H-thiazolo[5.4-b]azebin 2-1(E)3,4
The title compound was obtained from -dichlorostyryl l-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b]azevin (yield 13.0%).

Melting point 130-132°C I R (KBr) cm-': 3444, 320
g 1623 1525 1471, 1436137
5,1357,1274,1250.827N M R
(C D C (ls”) δ: 1.64 (28,
m), 1. 79 (2L m), 2.86 (2H
, i), 3, 05 (2H, m), 3. 91(
LH, br. s), 6. 51 (IH, d, J
= 12. 2Hz), 6. 65 (IH, d,
J=12. 2Hz). 7. 27 (IH, dd
, J = 1. 93Hz, 8. 22Hz),
7. 44 (IH, d, J = 8.22Hz)
,7. 66 (IH, d, J = 1.93Hz
). Elemental analysis value: C +aH 14N-S C Qt
Calculated value as: C, 55.39; H, 4J4; N
, 8.61; S, 9.86: C (1.21.80.
Actual value: C, 55.17; H, 4.38; N, 8
．． 54;S, 9.77;CQ. 21.80. Example 172 2-f(Z)-4-methoxystyryl)-5.6,7.
8-Tetrahydro-4H-thiazolo[5.4-b]azepine 2-((E)-4-
Metkinstyryl}-5.6,7.8-tetrahydride-
The title compound was obtained from 4H-thiazolo[5.4-b]azepine (yield: 9.6%).

Melting point 101-104°C I R (KBr) cm-': 3438, 327
8. 162g, 1606, 1544, 1509
, 1455. 143g, 1364, 1351,
1297, 1248, 1172, 1038. N.M.
R (C D Cl2,) δ: 1. 65 (2H,
m), 1. 77(2}1, m), 2.85(2
H. t, J = 5. 82Hz), 3. 01
(2H, t, J = 5.15Hz), 3.8
4 (3H, s), 6. 59 (IH, d. J=
12. 1Hz), 6. 66 (IH, d, J
= 12. 1Hz). 6. 91 (2H, d,
J=8. 82Hz), 7. 35 (2H, d
, J-8. 82Hz). Elemental analysis value: Calculated value as C + eH 1sN 2 SO: C, 67.10: H, 6.33; N, 9.
78:S, 11. 20, Actual value: C, 66.83; H, 6.34; N, 9
．． 69;S, 11. 08 Example 173 2-+1-(2-pyricyl)ethenyl l-5.6,7.
8-Tetrahydro 4H-thiazolo[5.4-b]azepine β-(2-biridyl)acrylic acid hydrochloride (3g, 16.
2 mmol) dimethylformamide solution (2Cltf
2), triethylamine (3.27 g. 32.3 mmol), 1-hydrobor-7penzotriazole hydrate (2.
72g, 17.8 mmol) and cooled with water.
Dicyclohexylcarbodiimide (3.67g, 17.
A solution of 8 mmol) in dimethylformamide (2M) was added dropwise. After stirring at room temperature for 2 hours, 3-amino-ε-cabrolactam (2.28 g, 17.8 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. Heavy backwater was added and extracted with a mixed solvent of chloroform and methanol. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography and purified with phosphorus pentasulfide (3.6 g,
1 in pyridine (20 m) with 6.2 mmol)
The mixture was heated and stirred at 20°C for 5 hours. After cooling to room temperature, aqueous sodium bicarbonate was added to the reaction mixture, extracted with a mixture of chloroform and methanol, dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified on silica gel column chromatography and recrystallized from ethyl acetate to give the title compound 63
5 mg (15.2%) was obtained.

Melting point 158-160' (recrystallized from ethyl acetate), l
R (KBr)cm': 3220, 1629
, 1583, 1555, 1513, 1471,
1445, 1419, 1367, 1355. 1
273, 959. NMR (CDC.) δ: l.
70 (2H, m), 1. 81 (2H.m),
292 (2H, t, J= 5.76Hz), 3
．． 13 (2H, t, J== 5.19Hz),
4.09 (1B, br.s), 7. 13(I
H, d. J = 16. 0Hz), 7. 14
(18, m), 7. 39 (IH, d, J =
7. 93Hz), 7. 51 (IH, d, J
= 16. 0Hz), 7. 65 (IH, dt,
J = 1. 83Hz, 7. 70Hz), 8.
57 (IH, d, J=4.76Hz). Elemental analysis value: C,. Calculated values as H,,N,S:
C, 65J4; H, 5.87; N, 16.33.
Actual value: C, 65.02; H, 5.93; N, 1
5.98. Example 174 2-+2.2-bis(4-diethylaminophenyl)ethenyl l-5.6,7.8-tetrahydro-4H-thiazolo[5.4-b coazebin by a method similar to Example 173 β1β′-bis(4
The title compound was obtained from -diethylaminophenyl)acrylic acid, 1-hydroxybenzotriazole-water'FD product, cyclohexyllupodiimide, 3-amino-epsilon caprolactam and phosphorus pentasulfide (yield 12.6%).

Melting point 173-175° (recrystallized from ethyl acetate). I
R(KBr)am-': 2972. 1608
．． 15g8, 1549, 1519, 1468,
1401. 1351, 1266. 11!13.
1154, 816. NMR (CDCi2s) δ: 1
．． 15 (6B, t, J = 7.05Hz),
1. 23 (6H, t, J = 7.05Hz).
1. 62 (2H, m), 1. 74 (2H.
m), 283 (2H, t, J= 5.64Hz
), 2. 97 (2H, t, J = 4.90
Hz). 3, 34 (4H, q, J= 7, 05H
z), 3. 42 (4H, Q, J= 7.05
Hz), 3.65 (IH, br.s). 6.
58 (2H, d, J=8.98Hz), 6.
76 (2H, dJ = 8.81Hz), 7.
04 (2H, d, J = 8.81Hz), 7
．． 15 (IH, s), 7.23 (2H, d, J
= 8. 98Hz). Elemental analysis value: C 1sH s
Calculated value as sN 4S: C, 73.37; H, 8
．． 07; N, 11.80; S, 6.75. Actual value: C,? 3.19; H, 8.15; N, 1
1,59;S,6.61. Example 175 21? (4-diethylaminophenyl)ethyl l-5.
6,7.8-Tetrahydro-4H-thiazoC'[5.4
-b] Azepine dihydrochloride 3-(4-diethylaminophenyl)probionic acid, 3-amino-ε-cabrolactam and phosphorus pentasulfide were purified by reaction in the same manner as in Example 18, and then neutralized with hydrogen chloride. The title compound was obtained (yield 12.2%).

Claims (1)

[Claims] 1. Formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, R^1 is a hydrogen atom or an aliphatic group which may have a substituent, respectively. , a carboxylic acid acyl group or a sulfonic acid acyl group, and R^2 represents a hydrogen atom, or an aromatic ring group or an aliphatic group each optionally having a substituent, or a salt thereof. An antihypertensive agent characterized by: 2. The antihypertensive agent according to claim 1, wherein R^1 is a hydrogen atom and R^2 is a phenyl group or an alkenyl group having 2 to 4 carbon atoms, each of which may have a substituent. 3. R^2 is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. R^5 and R^7 may be bonded to each other to form a ring. However, at least one of R^8 and R^7 is an aromatic ring group which may have a substituent. The antihypertensive agent according to claim 1, which is a group represented by the following. 4, R^2 has the formula -CH=CH-R^6' (wherein, R^6' represents an amino group or an aromatic ring group substituted with a substituted amino group, and has a cis-coordination with respect to the thiazoloazepine ring. The antihypertensive agent according to claim 1, which is a group represented by (a). 5. The antihypertensive agent according to claim 4, wherein R^6' is a phenyl group substituted with a mono- or cy-lower alkylamino group. 6. Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [ I ″] [In the formula, R^1 is a hydrogen atom, or an aliphatic group, a carboxylic acid acyl group, or a sulfonic acid group, each of which may have a substituent. An acyl group, R^2 is of the formula -CH=CH-R^6' (wherein, R^6' represents an amino group or an aromatic ring group substituted with a substituted amino group, and the cis-configuration is 7. The compound according to claim 6, wherein R^6' is a phenyl group substituted with a mono- or di-lower alkyl-substituted amino group.