DD247000A5 - PROCESS FOR THE PREPARATION OF IMIDAZONE DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of novel imidazole derivatives for use as medicaments. The aim of the invention is the provision of new imidazo derivatives with valuable pharmacological properties, in particular with antithrombotic and cardiovascular action, which are suitable, for example, for the treatment of heart failure. According to the invention, novel imidazo derivatives of the general formula (I) are prepared in which, for example: one or two of the radicals A, B, C or D is a nitrogen atom, another of the radicals A, B, C or D is a hydroxymethine group and the remaining radicals A , B, C or D methine groups, wherein one of these methine groups, if adjacent to a nitrogen atom, may be replaced by a methyne group substituted by a hydroxymethine group or an alkylmercapto group, R1 and R2 together with two intervening carbon atoms of the phenyl ring represent an alkoxy group optionally substituted Phenyl ring and R3 is a hydrogen atom or an alkoxy group. Formula (I)

Description

Berlin, 12. 6. 86 66 306 12

Process for the preparation of imidazo derivatives of the invention

The invention relates to a process for the preparation of novel Iraidazoderivate with valuable pharmacological properties, in particular with antithrombotic and cardiovascular properties, such as "B, with cardiotonic activity,

The compounds prepared according to the invention are used as medicaments, for example for the treatment of cardiac insufficiencies. ,

Characteristic of the well-known technical solutions

The literature (see, for example, Heterocyclic Systems with Bridgehead Nitrogen Atoms, Part 2 and The Chemistry of Heterocyclic Compounds Vol. 15, Editor: 1961 Interscience Publishers Inc., New York) has already disclosed several processes for the preparation of bicyclic imidazo derivatives ₃

Object of the invention

The aim of the invention is the provision of new imidazo derivatives with valuable pharmacological properties, in particular with antithrombotic and cardiovascular action, which are suitable, for example, for the treatment of heart failure.

16. JVVlSub -'- o J

4 7 0 0

Explanation of the essence of the invention

The invention has for its object to find new compounds with the desired properties and processes for their preparation.

According to the invention, new imidazo derivatives of the general formula

^R l

manufactured,

their Tautornere and their acid addition salts, ihsbesond'ere their physiologically acceptable acid addition salts with inorganic or organic acids which have valuable pharmacological properties, in particular antithrombotic and cardiovascular properties such as a cardiotonic and / or an effect on blood pressure.

In the above general formula I means

one or two of the radicals A, B, C or D is a nitrogen atom,

•. , 2 4 7 0

another of the radicals A, B, C or D is a hydroxymethine group and

the rest of the radicals A, B, G or D * methine groups, where one of these methine groups, if it is adjacent to a nitrogen atom, may be replaced by a hydroxymethine group or by a methine group substituted by an alkylmercapto group,

R, and FU together with two intervening carbon atoms of the phenyl ring one optionally by a

Alkoxy substituted phenyl ring and -R-, a hydrogen atom or an alkoxy group, or

one of the radicals R-,, R2 or R _{3 is} a hydroxy, phenyl. alkoxy, alkylmercapto, alkylsulfinyl, amino, alkylsulfonyloxy, sulfamyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonamido, N-alkyl-alkylsulfonamido, cyano, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group or,

when R2 and R- are not simultaneously hydrogen atoms or ·

if A, B, C and D together with the imidazole ring no Imidazo [l ', 2-b] pyridazine-6 (5H) -one, imidazo [1,2-c] pyr imide in 5 (6H) -one and 5 Alkylmercapto-imidazo [1,2-c] pyrimidine-7 (8H) -ones, also an alkoxy or alkylsulfonyl group,

a second of the radicals R,, R2 or _R3 is a W asserstof f atom, a hydroxy or alkoxy group, and

the last of the radicals R ₁ , R ₂ or R _{3 is} a hydrogen atom or an alkoxy group, it being possible for the alkyl part to contain 1 or 2 carbon atoms in all the radicals mentioned above.

The present invention thus relates in particular to the novel imidazo [1,2-a] pyrimidin-7-ones and -5,7-diones, imidazo [1.2-c] pyrimidin-5-ones and -7-ones, imidazo [2.1-f ] - [1.2.4] triazin-2-one, -4-one and -2,4-diones, imidazo [1,2-b] pyridazine-6-one, imidazo [1.2-a] [1.3.5] triazine -2-one, -4-one and -2,4-diones, imidazo [1,2-a] pyr'azin-6-one and -8-one ·, imidazo [1,2-d] [1.2.4] triazine-5-one, -8-one and -5,8-dione, • imidazo [1. 2-b] [1. 2. 4]. triazin-2-one and -3-one and imidazo [2.1-c] [1.2.4] triazin-3-ones, their tautomers and their acid addition salts, in particular their physiologically acceptable acid addition salts,

Thus, for the meanings mentioned in the definition of de, r radicals R 1 to R 3, there is thus obtained

for R ^ and R2 together with the phenyl ring. in particular the meaning of naphth-1-yl, naphth-2-yl, 2-methoxynaphth-1-yl, 3-methoxynaphth-1-yl, 4-methoxynaphthyl, 1-methoxy -naphth-2-yl. -, '3-methoxynaphth-2-yl, 4-methoxynaphth-2-yl, 5-methoxynaphth-2-yl, 6-methoxynaphth-2 -yl, 7-methoxynaphth-2-yl or 8-methoxynaphth-2-yl group and · .. _c

for R. the of the hydrogen atom, the methoxy or ethoxy group or

for R- which are the hydroxy, methoxy, ethoxy, benzyloxy, 1-phenylethoxy, 2-phenylethoxy, methylmereapto, ethylmercapto, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, amino, Methylsulfonyloxy, ethylsulfonyloxy, sulfamyl, methylamino.sulfonyl, ethylaminosulfonyl, dimethylaminosulfony.l, diethylaminosulfonyl, N-methylethylaminosulfonyl, methylsulfonamido, ethylsulfonamido, N-methylmethylsulfonamido N, N-ethyl-methylsulfonamido, N-methyl-ethylsulfonamido, N-ethyl-1-sulfonamido, cyano, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl or N-methyl-ethylaminocarbony!

for R _2, those of the hydrogen atom, the LYlethoxy- or ethoxy group and

for R-, those of the hydrogen atom, the methoxy or ethoxy group into consideration.

Preferred compounds of the above general formula I are those in which.

one or two of the radicals A, B, C or D is a nitrogen atom,

another of the radicals A, B, C or D is a hydroxymethine group and

the rest of the radicals A, B, C or D are methine groups, one of these 'methine groups, if it is adjacent to a nitrogen atom, may be replaced by a hydroxymethine group,' '.

R-, and R ₂ together with two intervening carbon atoms of the phenyl ring, a phenyl or methoxyphenyl ring and R, a hydrogen atom or a methoxy group or

one of R-, R ₂ or R _{3 is} a hydroxy, benzyloxy, methylmercapto, methylsulfinyl, methylsulfonyl, amino, methylsulfonyloxy, methylsulfonamido, N-methylmethylsulfonamido, sulfamyl, methylaminosulfonyl, dimethylaminosulfonyl , Cyano, aminocarbonyl, methylaminocarbonyl or dimethylaminocarbonyl group or,

if R ₂ and R ^ do not simultaneously denote hydrogen atoms or

when A, B, C and D together with the imidazole ring are not imidazo [1,2-b] pyridazine-6 (5H) -ones and imidazo [1,2-c] pyrimidine-5 (6H) -ones,

also a methoxy group,

a second .the radicals R-,, R2 or R, a Wasserstoffafom or a methoxy group and

the last of the radicals R ₁ , R ₂ or R _{3 is} a hydrogen atom or a methoxy group, but especially those compounds in which R 4 in the position and R in the 2-position, their tautomers and their acid addition salts, in particular their physiological 'Acid acid addition salts.

However, particularly preferred compounds of the above general formula I are those in which

A, B, C or D are defined as mentioned above,

R 4 in the 4-position is a cyano, dimethylaminocarbonyl, methylsulfonyloxy, methylsulfonamido, N-methylmethylsulfonamido, sulfamyl, methylaminosulfonyl or di-, methylaminosulfonyl group, or

when R ₂ and R ^ are not simultaneously hydrogen atoms, or

when A, B, C and D together with the imidazole ring are not imidazo [1,2-b] pyridazine-6 (5H) -ones and imidazo [1,2-c] pyrimidin-5 (6H) -ones,

also a methoxy group,

R ₂ in the 2-position, a methoxy group and

R, represent a hydrogen atom, their tautorra and their acid addition salts, in particular their physiologically acceptable acid addition salts. , -

Erfindungsgeraäß obtained the new compounds by the following methods: '.

a) reaction of a compound of the general formula

NH

(ID

in the

A, B, C and D are as initially defined, with a compound of the general formula

Q-Q // ^ w, (HI)

in the

R, R ^ and R ₃ are as hereinbefore defined and

X represents a nucleophilic leaving group such as a halogen atom, e.g., a chlorine or bromine atom.

.The reaction is conveniently carried out in a solvent or solvent mixture such as ethanol, isopropanol, benzene, glycol, glycol monomethyl ether, dimethylformamide or dioxane, for example at temperatures between 0 and 150 ⁰ C, preferably at temperatures between 20 and 100 ⁰ C. However, the reaction can also be carried out without a solvent.

b) For the preparation of compounds of the general formula I in which eirfer of the radicals R, R »or R _{3 represents} an alkylsulfonyloxy, alkylsulfonamido or N-alkyl-alkylsulfonamido group:

Reaction of a compound of the general formula

(IV)

in the

A, B, C and D are as defined above and the radicals R ', R''' and R ₃ ¹ with the exception of the alkylsulfonyloxy, alkylsulfonamido and N-alkyl-alkylsulfonamido group which are suitable for R-, R- or R-, However, one of the radicals R-, ', R ₂ ' or R ₃ ^{1 must represent} a hydroxy, amino, methylamino or ethylamino group, with a compound of the general formula

- SO-

- Y

in the

R is a methyl or ethyl group and Y is a nucleophilic leaving group such as a halogen atom or an alkoxy group, e.g. a chlorine or bromine atom, a methoxy, ethoxy or benzyloxy group.

The reaction is conveniently carried out in a solvent or solvent mixture such as water, methanol, ethanol, isopropanol, methylene chloride, ether, tetrahydrofuran,

Dioxan, dimethylformamide or benzene optionally in the presence of an acid-binding agent such as sodium carbonate, triethylamine or pyridine, the two latter can also be used as solvent ·, preferably at temperatures between 0 and 100 ⁰ C, for example at • temperatures between room temperature and 5O ⁰ C, performed.

c) For the preparation of compounds of general formula I, in which at least one of Rj_, R2 or R ^ is an alkoxy, phenylalkoxy or alkylmercapto group or

one of the radicals R

or

an N-alkyl-alkylsulphate

represent fonamido group:

Alkylation 'of a compound of the general formula

', (VI)

in the

A, B, C and D are as defined above and

and R., "for R,

or R-. mentioned in the beginning

However, at least one of the radicals R, ", R ₂ " or R ₃ ^{11 must represent} a hydroxy, mercapto or Alkylsulfonamidogruppe, with a compound of the general formula-

, (VII

in the

R4 is an alkyl or phenylalkyl group each having 1 or 2

Carbon atoms in the alkyl part and

Z is a nucleophilic exit group such as a halogen atom or a sulfonyloxy group, e.g. represents a chlorine, bromine or iodine atom, a methylsulfonyloxy, methoxysulfonyloxy or p-tolylsulfonyloxy group.

The reaction is conveniently carried out with an alkylating agent such as methyl iodide, ethyl iodide, dimethyl sulfate or methyl p-toluenesulfonate in a solvent such as tetrahydrofuran, dioxane, dimethylformamide, sulfolane, dimethyl sulfoxide or ethylene glycol dimethyl ether, optionally in the presence of an acid-binding agent such as potassium carbonate, potassium tert-butylate, triethylamine or pyridine, wherein the two latter can be used simultaneously as a solvent, at temperatures between 0 and. 100 ⁰ C, preferably at temperatures between 20 and 5O ⁰ C, carried out:

d) For the preparation of compounds of the general formula I in which one of the radicals R 1, R 2 or R 3, an aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfamyl, alkylaminosulfonyl or dialkylaminosulfonyl group represents:

Reaction of a compound of the general formula

, (VIII)

in the

A, B, C and D are as defined above, R '''andR''''denote R-, R ₂ and R ₃ except the aminocarbonyl, alkylaminocarbonyi, dialkylaminocarbonyl, sulfamyl, alkylaminosulfonyl or dialkylaminosulfonyl group have meanings mentioned above, W is a carbonyl or sulfonyl group and D is a nucleophilic leaving group such as a halogen atom or an alkoxy group, for example a chlorine atom, a methoxy or * ethoxy group, with an amine of the general formula

. ^ ^R5. '' - HN, (IX)

""" ^R 6

in the

Rc and Rf, which may be the same or different, each represents a hydrogen atom, a methyl or ethyl group.

The reaction is conveniently carried out in a solvent or solvent mixture such as water, methanol, ethanol, isopropanol, methylene chloride, ether, tetrahydrofuran, dioxane, dimethylformamide or benzene, optionally in the presence of an acid-binding agent such as sodium carbonate, triethylamine or pyridine, the two latter also being used simultaneously Solvent can be used, preferably at temperatures between 0 and 100 ⁰ C, for example at temperatures between room temperature and 50 ⁰ C performed.

If W is a carbonyl group, then U can also be a hydroxy group. In this case, the reaction is preferably carried out in the presence of a dehydrating agent, e.g. in the presence of ethyl chloroformate, thionyl chloride, phosphorus trifluoride, phosphorus pentoxide, N, N'-dicyclohexylcarboxylic acid,

bodiimide, N ₇ N ¹ -dicyclohexylcarbodiimide / N-hydroxysuccinimide, N ₇ N ¹ -carbonyldiimidazole or N, N'-thionyldiimidazole or triphenylphosphine / carbon tetrachloride, or an amino group activating agent, eg Phosphortr ic.hlor id, and optionally in the presence of a inorganic base such as sodium carbonate or a tertiary organic base such as triethylamine or pyridine, which may simultaneously serve as a solvent, at temperatures between -25 and 25O ⁰ C, but preferably at temperatures between -10 ⁰ C and the boiling temperature of the solvent used to be carried out Furthermore, water formed during the reaction can be separated by azeotropic distillation, for example by heating with toluene on a water separator, or by adding a desiccant such as magnesium sulfate or molecular sieve.

e) For the preparation of compounds of general formula I ₇ in which "the radicals A, B ₇ C and D are as defined above and one of the radicals R ₁ , R ₂ or R, represents an amino, hydroxy or aminocarbonyl group or R 1, R 2 and R 3 are as defined above and at least one of the radicals A, B, C or D represents a hydroxymethine group

Hydrolysis of a compound of the general formula

in the

R, R and R are as defined above and A ¹ , B ¹ , C and D ^{1 have} the meanings mentioned for A, B, C and D, but wherein either one of the above-mentioned methine groups by a hydrolytically cleavable radical as by a Halogen atom, an alkoxy or

- - 12 -.

Alkylrnercapto group, e.g. a chlorine or bromine atom, a methoxy or methylmercapto group, is substituted or one of the radicals R-, R-j or R ^ must represent an alkanoylamino, cyano or alkylsulfonyloxy group.

The reaction is conveniently carried out either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid or trichloroacetic acid or in the presence of a base such as sodium hydroxide or potassium hydroxide or the alkali salt of a corresponding alcohol, in the melt or in a suitable solvent such as water, water / methanol, ethanol , Water- / ethanol, water / I sopropanol or water / dioxane, at temperatures between -10 and 120 ⁰ C, for example at temperatures between room temperature and the boiling temperature des.Reaktionsgemisches performed.

However, the partial hydrolysis of the cyano group is preferably carried out with concentrated sulfuric acid or with an alkali metal hydroxide in the presence of hydrogen peroxide, e.g. with sodium hydroxide / hydrogen peroxide, conveniently carried out at room temperature.

f) For the preparation of compounds of the general formula I in which

one or two of the radicals A, B, C or D is a nitrogen atom, another of the radicals A, B, C or D is a hydroxymethine or alkylmercaptomethine group and

the remaining radicals A, B, C or D represent methine groups:

Reductive cleavage of one or two radicals of a compound of the general formula

in the

R, Rp and Rj are as defined above and the radicals A ", B", C "and D" have the meanings mentioned for A, B, C and D, but at least one of the abovementioned 'methine groups is a reductive cleavable group as must be substituted by a halogen atom or an alkylmercapto group.

The reductive cleavage is preferably carried out by means of hydrogenolysis. This is conveniently carried out in a solvent such as methanol, ethanol, isopropanol, glacial acetic acid, ethyl acetate, dimethylformamide or water optionally in the presence of a mineral acid such as hydrochloric acid or hydrobromic acid at temperatures between -1O ⁰ C and 100 ⁰ C, preferably at 0 ⁰ C to 60 ⁰ C. in the presence of a catalyst such as Raney nickel, platinum, platinum oxide or palladium on carbon. An optionally present benzyloxy group is converted during the reaction into a hydroxy group.

If, according to the invention, a compound of the general formula I in which one of the radicals R 1, R 2 or R 3 represents an amino group, this can be converted via the corresponding diazonium salt into a compound of the general formula I in which one of the radicals R 1 , R, or R- represents a cyano group.

The subsequent reaction of a diazonium salt, for example of the hydrosulfate in sulfuric acid or of the hydrochlorides, in the presence of the corresponding copper (I) salt such as copper (I) cyanide / hydrochloric acid, is at leicht'erhöhten temperatures, eg, at temperatures between 15 ° C and 100 ⁰ C performed. The required diazonium salt is expediently dissolved in a suitable solvent, for example in water / hydrochloric acid, methanol / hydrochloric acid, ethanol / hydrochloric acid or dioxane / hydrochloric acid, by diazotization of a corresponding amino compound with a nitrite, for example sodium nitrite or an ester of nitrous acid, at low temperatures , for example, at temperatures between -1O ⁰ C and 5 ⁰ C, prepared.

Furthermore, the compounds of the general formula I obtained according to the invention can, if desired, be converted into their physiologically tolerated acid addition salts with inorganic or organic acids. Examples of suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, tartaric acid, citric acid, lactic acid, maleic acid or methanesulfonic acid.

The compounds of the general formulas II to XI used as starting materials are known from the literature in some cases or are obtained by processes known from the literature.

Thus, for example, the compounds of the general formulas IV, VI, VIII, X and XI which are used as starting materials are obtained by reacting a corresponding amino compound with a corresponding a-bromoacetophenone and optionally subsequent chlorosulphonation.

As already mentioned, the new compounds of the general formula I whose IH tautomers and their physiologically tolerated acid addition salts have superior phar-

macro-characteristics, in particular antithrombotic and cardiovascular properties such as cardiotonic and / or an effect on blood pressure.

For example, the compounds were

A = 2- (4-dimethylaminosulphonyl-phenyl) -8H-imidazo [Γ, 2-a] -pyrimide in-7-one,

B = 2- (4-methoxyphenyl) -7H-imidazo [1,2-a] pyrazine-8-one,

C = 7- (4-methoxy-phenyl) -IH, 3H-imidazo [1,2-a] [1.3.5] triazine-2,4-dione, "

D = 2- (2-methoxy-4-methylsulfonyl-oxyphenyl) -SH-imidazo • [1; 2-a] pyrimidin-7-one,

E = 2- (2-methoxy-4-cyanophenyl) -8H-imidazo [1,2-a] pyrimidin-7-one, '' '

F = 2- (2-methoxy-4-dimethylaminosulfonylphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one,

G = 2- (2-methoxy-4-methylaminosulfonylphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one,

H = 2- (2-i-lethoxy-4-dimethylaminocarbonylphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one and

I = 2- (2-methoxy-4-methylsulfonyloxyphenyl) -7H-imidazo [1,2-a] pyrazine-8-one

examined for their biological properties as follows:

Determination of the positive inotropic effect on desalinated guinea pigs

The investigations were on. despinalized guinea pigs performed. The animals were ventilated with 50% O ₂ + 50% N ₂ . Arterial blood pressure was measured in the right carotid artery with a Bell and Howell pressure transducer (4-327-1). To measure the positive inotropic effect, the pressure in the left ventricle (LV) was measured with a catheter tip manometer (Millar PR-249). By means of a differentiator, LV-dp / dtmax was obtained. The substances to be examined were injected into a jugular vein. The solvent used was 0.9% NaCl + Pölydiol "200

Each substance was tested on 3 guinea pigs. The doses were 0.1-3 mg / kg i.V ... The following table contains the mean values at 1 mg / kg i.V ..

substance dose Increase in mg / kg i.v. LV dP / dt max A 1 32% B 1 45% C 1 . 86% D , 1 63% e 1 44% F 1 47%. G 1 75% H 1 33% • I .1 98%

The new compounds are well tolerated, so in the study of substances A to I up to a dose of 3 mg / kg i. v. No herpes - toxic effects resp

 Circulatory damage can be observed *

Because of their pharmacological properties, the compounds according to the invention of general formula I and their physiologically tolerated acid addition salts are suitable for the treatment of cardiac insufficiencies of different origin, since they increase the contraction force of the heart and, in some cases, facilitate the emptying of the heart by lowering blood pressure.

For this purpose, the novel compounds and, whose physiologically acceptable acid addition salts, optionally in combination with other active substances _{f, can be incorporated} into the customary pharmaceutical application forms such as tablets, dragees, powders, suppositories, suspensions, ampoules or drops. The single dose here is 1 to 4 times daily 0.1 to 15 mg / kg body weight, but preferably 3-10 mg / kg body weight.

Working Example

The following examples are intended to explain the invention in more detail:

example 1

2- (4-methylsulfonyloxy-phenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

2.2 g (0.02 mol) of 2-amino-4-hydroxy-pyrimidine and 5.9 g (0.02 mol) of α-bromo-4-methylsulfonyloxy-acetophenone are stirred in 50 ml of dimethylformamide at room temperature. After 6 hours, the clear solution is evaporated to dryness in vacuo and the crude product obtained via a column (silica gel, particle size: '0.2-0.5 mm, eluant = Methylenchlo- * ¹ rid: ethanol mixtures), cleaned. The. Desired end product is recrystallized from ethanol / dimethylformamide.

Yield: 37.7% of theory,

Melting point: 246 to 248 ⁰ C

Calc .: C · 5Γ, 14 H 3.63 N 13.76 S 10.50 Gef. 51.06 3.58 13.76 10.70

Example 2

6- (4-Methylsulfonyloxyphenyl) -3H-imidazo [2,1-f] [1,2,4] triazin-4-one

425 mg (1.86 mmol) of 6- (4-hydroxyphenyl) -3H-imidazo [2,1-f] - [1,2,4] triazin-4-one are dissolved in 20 ml of sodium hydroxide solution. At room temperature, 456 mg of methanesulfonic acid chloride are added and stirred for 2 hours at room temperature. The pale yellow clear solution is neutralized in the cold with 2N hydrochloric acid. The precipitated white-gray precipitate is filtered off, washed with water, dried and dissolved in methylene chloride / ethanol = 1: 1; 10 g of silica gel are added and evaporated to dryness, the evaporation residue

is placed on a silica gel column and eluted first with methylene chloride, later with methylene chloride / ethanol = 50: 1 and 25: 1. The desired eluates are concentrated, the crystalline 'residue is triturated with ether, suction filtered and dried in vacuo at 5O ⁰ C

Yield: 9.65% of theory, Melting point: 304-306 ⁰ C. -

Calc .: C 47.07 H 3.29 N 18.30 S 10.45 Gef. 47.44 3.58 18.04 10.06

, Example "" 3 "'"'"

2- (3-dimethylaminosulfonyl-4-methoxy-phenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

a) 2- (3-Chlorosulfonyl-4-methoxyphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

1.5 g (6.2 mmol) of 2- (4-methoxyphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one are added at 0-5 ⁰ C with stirring in 15 ml of chlorosulfonic acid. After 3 hours 'standing at room temperature, the reaction mixture is poured into ice-water and the precipitated product is filtered off with suction and dried.'

b) 2- (3-Dimethylaminosulfonyl-4-methoxyphenyl) -6H-imidazo [ 1,2 -c] pyrimidin-5-one

1.5 g (4.4 mmol) of the product obtained under a) are taken up in 30 ml of aqueous dimethylamine solution (40% strength) and heated to 50 ^° C. After 30 minutes, the clear solution is diluted with water, extracted with ethyl acetate and the combined extracts are evaporated after drying over sodium sulfate in vacuo. The crude product obtained is crystallized from ethanol.

/ · * A -j «λ α - 20 -

Yield: 73.3% of theory, Melting point: 288-290 ⁰ C Calc .: C 51.71 H 4.63 N 16.08 S 9.20 Found 51.69 '· 4.57 16.24-9. 25

Example 4

2- (4-hydroxy-2-methoxy-phenyl) -5H-imidazo [1,2-b] pyridazin-6-one

0.4 g (1.13 mmol) of 6-chloro-2- (2-methoxy-4-methylsulfonyloxyphenyl, 1-imidazo [1,2-b] pyridazine is added in 30 ml of 4N for 6.5 hours Potash solution heated to reflux. After filtration of the hot solution, the product is obtained by acidification with concentrated hydrochloric acid. Yield: 100% of theory, m.p .:> 250 ^° C. NMR spectrum (dimethyl sulfoxide / deuteromethanol): OCH ₃ : 3.95 ppm (s) 3H H on the phenyl ring: 6.65 ppm (dd) IH

6.7 ppm (d.) IH 7.82 ppm (d) IH-H at 3-position ": 8.45 ppm (s). IH 7 position: 8.3 ppm (d). IH 8-position: 7 , 4 ppm (d) IH UV spectrum (ethanol): 256 nm (0.19)

352 nm '(0.19)

(Ethanol + KOH): 275 nm (0.26) "x 370 nm (0.19)"

- 21 -

Example 5

6- (4-Hydroxy-phenyl) -3H-imidazo [2, 1-f] [1,2,4] triazin-4-one

1.37 g (0.005 mmol) of 6- (4-hydroxy-phenyl) -2-methylmercapto-3H-imidazo [2, 1-f] [1,2,4] triazin-4-one is dissolved in 60 ml of ethanol dissolved, mixed with 5 g of Raney nickel and shaken for 7 hours in a Parr apparatus at 8O ⁰ C at a hydrogen pressure of 5 bar. The mixture is then filtered off from the catalyst, combined with 20 g of silica gel, evaporated and the residue obtained is purified over a silica gel column. First, it is eluted with methylene chloride, later with methylene chloride / ethanol = 50: 1 and 25: 1. The eluates containing the desired substance are evaporated, the crystalline residue is triturated with ether, suction filtered and dried in vacuo at 50 ⁰ C.

Yield: 18.4% of theory, m.p .: 314-316 ° C

Calc .: C 57.89 H 3.53 N '24, 55 Cons .: 57.70 3.74 24.50

Example 6

2- (4-Dimethylaminosulfonylphenyl) -8H-imidazo [l, 2-a] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-4-dimethylaminosulfonyl-acetophenone analogously to Example 1. Yield: 27.3% of theory,

Melting point: 300-302 ⁰ C ''

Calc .: C 52.82 H 4.43 N 17.60 S 10.07 Found: 52.76 4.65 17.60 10.27

- 22 Example 7

2- (4-dimethylaminosulphonyl-phenyl) -6H-imidazo [1,2-c] pyrimidin-5-one · - ''

Prepared from 2-hydroxy-'4-amino-pyr imidine and α-bromo-4-dimethylaminosulfonyl-acetophenone. analogously to Example 1.

Yield: 28.7% of theory,

Melting point: 246-248 ° C

Calc .: G 52.82 H 4.43 N 17.60 S 10.07 Gef.: 52.41 4.51 17.55. 10,19 '

Example 8

2- (4-methoxy-phenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-4-methoxy-acetophenone analogously to Example 1.

Yield: 29.2% of theory,

Melting point: 290-295 ⁰ C

Calc .: C 64.72 H 4.60 N 17.42 Vessel: 64.60 4.60 17.16

Example 9

2- (4-Methylsulfonamidophenyl) -6H-imidazo [1,2-c] pyrimidine · 5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-4-methylsulfonamido-acetophenone analogously to Example 1. Yield: 34.6% of theory, melting point: 293-295 ° C

Calc .: C 49.44 H. 4.37 N 17.38 S 10.54 Vessel: 49.41 4.10 17.00 10.71

Example 10

2- (4-Methylsulfonyloxyphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one '·

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-4-methylsulfonyl-acetophenone analogously to Example 1.

Yield: 29.6% of theory,

Melting point: 302-305 ^0C. Calc .: C 51.14 H 3.63 N 13.76 S 10.50 F .: 50.88 3.70 13.68 .10.53

Example 11

2- (4-methoxyphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-6 · methoxy-acetophenone analogously to Example 1.

Yield: 36.9% of theory,

Melting point: 255-258 ⁰ C

Ber. : C 64.72 H 4.60 N 17.42 Gef.: 64.81 4.60 17.67

Example 12

7- (4-Methylsulfonamido-phenyl) -IH, 3H-imidazo [1,2-a] [1,3,5] triazine-2,4-dione

Prepared from 6-amino-1H, 3H- [1,3,5] triazine-2,4-dione and α-bromo-4-methylsulfonamido-acetophenone analogously to Example 1.

Yield ': 28% of theory,

Melting point; > 300 ⁰ C

R _f value: 0.60 (methylene chloride / methanol = 7: 3;

Mass spectrum: M: '321 m / e.

UV spectrum (ethanol) -: 278 nm (0.18)

Example 13 >

7- (4-methoxyphenyl) -1H, 3H-imidazo [1,2-a] [1,3,5] triazine * 2,4-dione

Prepared from 6-amino-1H, 3H- [1,3,5] triazine-2,4-dione and α-bromo-4-methoxy-acetophenone analogously to Example 1.

Yield: 31% of theory,

Melting point:> 300 ^° C.

R _f value: 0.70 (methylene chloride / methanol = 7: 3;

Mass spectrum: M: 258 m / e

UV spectrum (ethanol): 274 nm (0.37)

Example 14

2- (4-methylsulfonamido-phenyl) -7H-imidazo [1,2-a] pyrazin-8-one

Prepared from 3-amino-1H-pyrazine-2-one and α-bromo-4-methyl

sulfonaraido-acetophenone analogously to Example 1.

Yield: 15% of theory,

Melting point: 323 ^° C.

Calc .: C 51.31 H 3.98 N 18.12. S 10,54 Gef.: '50,97 4,32 18,12 10,78

Example 15 2- (4-Methoxyphenyl) -7H-imidazo [1,2-a] pyrazine-8-one

Prepared from 3-amino-1H-pyrazine-2-one and α-bromo-4-methoxy-acetophenone analogously to Example 1.

Yield: 25% of the theory,. ·

Melting point:> 300 ^° C.

R _f value: 0.65 (acetonitrile / formic acid = 9: 1; SiO ₂ ) calc .: C 64.72 H 4.60 N 17.42 Gef.: 65.00 4.65 16.43

Example 16 <-

2- (4-Methylsulfonyloxyphenyl) -6H-imidazo [1,2-d] [1,2,4] triazin-5-one

Prepared from 5-amino-2H- [1,2,4] triazine-3-one and α-bromo-4-methylsulfonyloxy-acetophenone in dimethylformamide analog

Example 1.

Yield: 40.2% of theory,

Melting point: 286-287 ° C ·

Calc .: C 47.07 H 3.29 N "18.18 S 10.42

Gef .: 47.10 3.28 18.37 10.69

Example 17 2- (4-Methoxyphenyl) -6H-imidazo [1,2-d] [1,2,4] triazirt-5-one

Prepared from 5-amino-2H- [1,2,4] triazin-3-one and α-bromo-4-methoxy-acetophenone in dimethylformamide analogously to Example Yield: 42.4% of theory,

Melting point: 309-312 ⁰ C

Calc .: C. 59.50 H 4.29 N 23.13 Gef; : 59.60 '4.16 23.59

Example 18

2- (4-methylsulfonamido-phenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-4-methylsulfonamido-acetophenone analogously to Example 1.

Yield: 31.1% of theory,

Melting point: 308-309 ⁰ C

Calc .: C 51.31 H 3.98 N 18.61 S 10.54 F .: 51.00 3.98 18.08 10.65

Example 19 .

2- (2-Methoxy-4-methylsulfonyloxyphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-methylsulfonyloxy-acetophenone analogously to Example 1.

ν 4 7 η λ η

Yield: 20% of theory, Melting point: '264-266 ⁰ C Calc .: C 50.14 H 3.91 N 12.53 S 9.56 Found:. 49.71 3.95 12.19 9.95

Example 20

2- (2,4-dimethoxyphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and a-bromo-2, 4-dimethoxy-acetophenone analogously to Example Yield: 23% of theory, Melting point: 258-260 ⁰ C Calc .: C 61.98 H 5.85 N 15,49 Gef.: 62,08 5,86 '15,24

Example 21

2- (4-Methylsulfonamido-phenyl) -5H-imidazo [1,2-b] pyridazin-6-one

Prepared from 2- (4-methylsulfonamido-phenyl) -6-methylsulfonyloxy-imidazo [1,2-b] pyridazine and sodium hydroxide solution analogously to Example 4.

Yield: 39.2% of theory, melting point: 315-318 ° C. Calc .: '. C 51.31. H 3.97 N 18.41 S 10.54 F .: 51.43. 4,13 18,20 10,50

·. ? 4 7 O O

Example 22

2- (4-Amino-phenyl) -5H-imidazo [1,2-b] pyridazin-6-one

Prepared from 2- (4-acetamido-phenyl) -6-chloro-imidazo [1,2-b] pyridazine and potassium hydroxide analogously to Example 4. 'Yield: 95.2% of theory, melting point:> 330 ⁰ C Analysis of Monohydrate: Calc .: C 59.02 H 4.95 N 22.95 'Gef.: 59.47 4.87 22.63

Example 23

2- (4-Methoxy-2-methylsulfonamido-phenyl) -5B -imidazo [1,2-b] pyridazin-6-one. -

Prepared from 6-chloro-2- (4-methoxy-2-methylsulfonamidophenyl) -imidazo [1,2-b] pyridazine and sodium hydroxide solution analogously to Example 4.

Yield: 78% of theory, melting point: 267-276 ° C

Calc .: C 50.29 H 4.22 N 16.76 S 9.59 Gef.: 49.97 4.10 16.95 9.83

Example 24

2- (2-Methoxy-4-methylsulfonytoxy-phenyl) -5H-imidazo [1,2-b] pyridazin-6-one

Prepared from 2- (2-methoxy-4-methylsulfonyloxyphenyl) -6-

Ί & / 0 0

Methylsulfo'nyloxy-imidazo [1, 2-b] pyridazine and ethanolic hydrochloric acid analogously to Example 4.

Yield: 55% of theory,

Melting point: 265-275 ⁰ C (decomposition) ·.

Calc .: C 48.82 H 4.10 N 12.20 F .: 48.27 4.11 '11.34

Example 25

6- (4-hydroxyphenyl) -p-methyl-adenapto-SH-imidazo [2, 1-f] -1- [lambda], 2,4] triazin-4-one

Prepared from 6- (4-methoxyphenyl) -2,4-bis (methylmercapto) imidazo [2,1-f] [1,2,4] triazine and concentrated hydrochloric acid analogously to Example 5.

Yield: 47.5% of theory, Melting point: 307-309 ⁰ C.

Calc .: C 52.56 H 3.68 N 20.43 S 11.70 F .: 52.26 3.78 20.66 11.73

Example 26

7- (4-Methylsulfonyloxyphenyl) -1H-imidazo [1,2-a] fl.3.5] triazin-2-one

Prepared from 2-amino-4-hydroxy-l, 3,5-triazine and α-bromo-4-methylsulfonyloxy-acetophenone analogously to Example 1.

Yield: 29.8% of theory,

Melting point: 234-236 ° C

Calc .: C 47.05 H 3.29 N 18.29 S 10.47

Gef .: 47.03 3.27 18.66 10.49

Example 27

7- (4-dimethylaminosulfonyl-phenyl) -IL-imidazo [1,2-a] [1.3.5; triazine-2-one

Prepared from 2-amino-4-hydroxy-l, 3,5-triazine and α-bromo-4-dimethylaminosulfonyl-acetophenone analog'Example 1.

Yield: 39.1% of theory,

Melting point: 283-285 ⁰ C

Calcd .: C: 48.89 H 4.10 N 21.93 S 10.04 Gef.: 49.32 4.30 .21.74 10.23

Example 28

- j H:. 2- (2-methoxy-4-methylsulf οnamido-phenyl) .- imidazo [1, 2-a] pyr imidine-7-one ^l

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-2-methoxy-4-methylsulfonamido-acetophenone analogously to Example 1.

Yield: 36.6% of theory,

Melting point: 314-316 ° C '

Analysis of the monohydrate:

Calc .: C 47.71 H 4.57 N 15.90 S 9.09 Gef.: 47.80 4.37 15.89 9.34

Example 29 .

2- (2-Methoxy-4-methylsulfonylphenyl) -7H-imidazo [1,2-a] pyrazine-8-one

Prepared from 3-amino-1H-pyrazine-2-one and α-bromo-2-methoxy-4-methylsulfonyl-acetophenone analogously to Example 1.

Yield: 56% of theory, melting point t-: 283-286 ⁰ C (decomposition) UV spectrum (ethanol): 268 nm (0.56)

3 08 nm (0.48) 320 nm (0.45)

Example 30

7- (2-Methoxy-4-methylsulfonyl-phenyl) -IH, 3H-imidazo [1,2-a] [1.3.5] triazine-2,4-dione

Prepared from 6-amino-1H, 3H- [1.3.5] triazine-2,4-dione and α-bromo-2-methoxy-4-methylsulfonyl-acetophenone analogously to Example 1.

Yield: 22% of theory, m.p .:> 300 ^° C. Mass spectrum: M: 336 m / e UV spectrum (ethanol + NaOH): 245 nm (0.46)

330 nm (0.28)

Example 31

7- (2-methoxy-4-methyIsulfonyloxy-phenyl) -lH, 3H-imidazo [1,2-a] [1,3,5] triazine-2,4-dione

Prepared from 6-amino-1H, 3H- [1.3.5] triazine-2,4-dione and a-bromo-2-methoxy-4-methylsulfonyloxy-acetophenone analogously to Example 1.

Yield: 22% of theory, melting point:> 300 ^° C. Ber. : C 44.32 H 3.43 N 15.90 Gef.: 44.51 3.55 15.78 Mass spectrum: M: 352 m / e UV spectrum (ethanol): 290-304 - (0.09)

, - 32 Example 32

2- (2-Methoxy-4-methylsulfonyloxyphenyl) -7H-imidazo [1. 2-a] pyrazine-8-one,.,. '. -

Prepared from 3-amino-1H-pyrazine-2-one and α-bromo-2-methoxy-4-methylsulfonyloxy-acetophenone analogously to Example Yield: 43% of theory,

Melting point: 273-275 ⁰ C.

Calc .: C 50.11 H 3.91 N 12.52 S 9.55 Gef.: 49.90 3.99 12.82 9.61

Example 33 '' · ·

2- (2-Methoxy-4-methylsulfonamido-phenyl) -6H-imidazo [1,2-c] pyrimidine-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-methylsulfonamido-acetophenone analogous to Example Yield ': -28.4% of. Theory,

Melting point: 240-243 ⁰ C

Calc .: C 50.29 H 4.22 N 16.76 S 9.59 F .: 49.90 4.31 16.54 'x 9.65

Example 34

7- (2-Methoxy-4-methylsulphonamidophenyl) -1H-imidazo [1,2-a] [1.3.5] triazin-2-one

Prepared from 2-amino-6-hydroxy- [1,3,5] triazine and α-bromo-2-methoxy-4-methylsulfonamido-acetohenone analogously to Example Yield: 25.4% of theory,

Melting point: 245-248 ° C

Calc .: C 46.56 H. 3.91 N 20.09 S 9.56

Gef.: 46.31 4.03 20.38 9.37

Example 35

2- (2-Methoxy-4-methylsulfonyloxyphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from 2-amino-4 - hydroxy-pyrimidine and a-bromo-2-methoxy-4-methylsulfonyloxy-acetophenone analogously to Example Yield: 24% of theory, - · Melting point: 253-255 ⁰ C.

Calc .: C 50.14 H 3.90 N 12.53 S 9.56 Gef.: 50.30 3.73 12.33 9.44

Example 36

2- (2-Methoxy-4-methylaminosulfonylphenyl) -6H-imidazo [1,2-c] pyrimidine-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-methylaminosulfonyl-acetophenone analogously to Example Yield: 37% of theory,

Melting point:> 300 ^° C.

Calc .: C 47.91 H 4.57 N 15.90 S 9.09

Gef .: 48.00 4,43 15,79 9,27

^ I 7 O O

Example 37

2- (2-Methoxy-4-methylsulfonamido-phenyl) -6H-imidazo [1,2 -c] pyrimidin-5-one "

Prepared from 2-hydroxy-4-amino-pyriraidine and α-bromo-2-methoxy-4-methylsulfonamido-acetophenone analogously to Example Yield: 22.7% of theory,

Melting point: "> 300 ^° C

C ..: C 47,71 H 4,57 N 15,90 S 9,09 Vat.: '"47,45 · 4', 46 .15,75 8,92

Example 38

7- (2-Methoxy-4-methylaminosulfonylphenyl) -1H-imidazo [1,2-a] [1,3,5] triazin-2-one

Prepared from azacytosine and .a-bromo-2-methoxy-4-methylaminosulfonyl-acetophenone analogously to Example 1.

Yield: 43.7% of theory,

Melting point:> 300 ^° C.

Calc .: C 44.18 H 4.28 N 19.82 S 9.07 Gef.: 43.91. 4,42 19,46 9,12

Example 39

7- (2-methyl-4-methylsulfonamido-phenyl) -triazin-2-one

Prepared from azacytosine and α-bromo-2-methoxy-4-methylsulfonamido-acetophenone analogously to Example 1.

Yield: 40.6% of theory, melting point:> 300 ^° C.

Calcd .: C, 44.18, H, 4.28, N, 19.82; S, 9.07; V: 43.99, 4.35, 20, 02, 9, 12

Example 40

2- (2-methoxy-4-cyano-phenyl) -8H-imidazo [l, 2-a] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and a-bromo-2-methoxy-4-cyan'o-acetophenone analog Step Example 1 Yield: · 42.1% of theory, Melting point: 308-310 ⁰ C Ber. : C, 61.74, H, 4.03, N, 20.37, viz.: · 62.01, 4.03, 20.03

Example 41

2- (2-methoxy-4-dimethylaminocarbonyl-phenyl) -6H-imidazo [l, 2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-dimethylaminocarbonyl-acetophenone analogously to Example

Yield: 21.6% of theory,

Melting point: 245-250 ⁰ C

Calc .: C 61.53 H 5.16 N 17.94 Vessel: "61.26, 5.19, 17.98

- 36 Example 42 .

2- (2-Methoxy-4-methylaminocarbonyl-phenyl) -8H-imidazo [1,2-pyrimidyl-7-one ·.

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-2-methoxy-methylaminocarbonyl-acetophenone analog. Example 1. Yield: 41.6% of theory, melting point of the hydrate: 272-274 ° C. C 56.96 H 5.10 N 17.71 Vessel: -56.70 x 4.99 18.01

Example 43

2- (2-Methoxy-4-methylaminocarbonylphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-methylaminocarbonyl-acetophenone analogously to Example 1.

Yield: 39.2% of theory,

Melting point: 277-279 ⁰ C

Ber. : C 58.62 H 4.92 N 18.23 Gef.: 58.58 4.95 18.25

Example 44

2- (2-Methoxy-4-dimethylaminocarbonylphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one.

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-2-methoxy-4-dimethylaminocarbonyl-acetophenone analogously to Example 1.

; ' 4 / UUU

Yield: 38.1% of. Theory, m.p .: 248-251 ° C

Calc .: C -61.53 H 5.16 N "17.94 Vessel: 61.65 5.17 '17./81

Example 45

2- (2,4-dimethoxy-5-dimethylaminosulphonyl-phenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from 2- (2,4-dimethoxyphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one and chlorosulfonic acid and then reacted with 40% dimethylamine analogous to the Example Yield: 45% of theory,

Melting point: "300-303 ⁰ C

Ber.i C 48.47 'H 5.08. N 14,90 S 8,62 F .: 48,41 5,29 14,90 '8,62

Example 46

7- (2-Methoxy-4-dimethylaminosulfonylphenyl) -1H-imidazo [1,2-a] [1,3,5] triazin-2-one

Prepared from azacytosine and α-bromo-2-methoxy-4-dimethylaminosulfonyl-acetophenone analogously to Example 1.

Yield: 28% of theory,

Melting point: 285-287 ° C

Calc .: C 45.76 H 4.66 N 19.06 'S 9.18

Gef.: 45.52 4.68 18.91 9.67

- 38 Example 47

2- (2-methoxy-4-sulfamyl-phenyl) -8H-imidazo [1,2-a] -pyrimidin-7-οη

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-2-methoxy-4-sulfamyl-acetophenone analogously to Example 1.

Yield: 43.7% of theory,

Melting point: 284-286 ⁰ C

Calc .: C 48,74 H 3,78 N 17,49 S "10,01 Found: '48,69 3,87 17,30' 10,1 * 7

Example 48

2- (2-Methoxy-4-sulfamoyl-phenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-sulfamyl-acetophenone analogously to Example 1.

Yield: 39.4% of theory,

Melting point: 284-286 ° C

Calc .: C 48.74 H 3.78 N 17.49 S 10.01 Found: 48.59 3.97 17.40 10.21

Example 49

2- (2-Methoxy-4-methylaminosulfonylphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-2-methoxy-4-methylaminosulfonyl-acetophenone analogously to Example

Ι; Ij "ft

Yield: 22% of theory, Melting point: 300-302 ⁰ C Calc .: C 50.28 H 4.22 N 9.59 Found .16,76 S:. '50,15. 4,39 16,65> 9,68

Example 50

2- (2-Methoxy-4-aminocarbonyl-phenyl) -8H-imidazo [1,2-a] pyridine-7-one hydrate

Prepared from 2-Amlno-4-hydroxy-pyrimidine and a-bromo-2-methoxy-4-aminocarbonyl-acetophenone analogously to Example Yield: 35% of theory, Melting point:> 330 ⁰ C

Calc .: C 55.63 H 4.67 N 18.53 Gef.:. 55.38 4.58 18.29

Example 51

7- (2-Methoxy-4-cyanophenyl) -1H-imidazo [1,2-a] [1,3,5] triazin-2-one.

Prepared from azacytosine and α-bromo-2-methoxy-4-cyano-acetophenone analogously to Example 1.

Yield: "36.8% of theory, Melting point: 270-272 ⁰ C Calc .: C 51.48 H 3.98 N 23.09

Gef.: 51.80 '3.98 22.80

Example 52 2- (2,4-Dimethoxyphenyl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and a-bromo-2,4-dimethoxy-acetophenone analogously to Example Yield: 55.8% of theory, Melting point: 270-273 ⁰ C Calc .: C 61.99 H .4 , 83 'n 15,49 Gef .: 61,68 4,91 15,46

Example 53

2- (2-Methoxy-4-aminocarbonylphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and a-bromo-2-methoxy-4-aminocarbonyl-acetophenone analogously to Example Yield: 30% of theory, Melting point: 240-245 ⁰ C Calc .: C 59.15 .. H 4,26 N 19,71 F .: 59,39 4,21 19,62

Be itpiel 54

2- (2-methoxy-4-dimethylaminosulfonyl-phenyl) -δΗ-rmidazo- [1,2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amino-pyrimidine and α-bromo-2-methoxy-4-dimethylaminosulfonyl-acetophenone analogously to Example 1.

/ υ ν υ

- 41 -

Yield: 30.6% .the theory,

Melting point: 219-221 ⁰ C

Calcd .: C, 49.71, H, 4.98, N, 15.37, S, 8.97, v / v.: · · 49.69, 5.01, 15.27, 9.03

Example 55

2- (2-methoxy-4-cyano-phenyl) -6H-imidazo [l, 2-c] pyrimidin-5-one

Prepared from 2-hydroxy-4-amine-pyrimidine and α-bromo-2-methoxy-4-cyano-acetopheno.n analogously to Example 1.

Yield: 27% of theory,

Melting point: 308-310 ⁰ C

Calc .: C 61.08 H '4.02 N 20.35 Vessel: 61.15 3.98 19.97

Example 56 .

2- (2-Methoxy-4-dimethylaminosulfonylphenyl) -SH-imidazo [1,2-q] pyrimidin-7-one

Prepared from 2-amino-4-hydroxy-pyrimidine and α-bromo-2-methoxy-4-dimethylaminosulfonyl-acetophenone analogously to Example

Yield: 39.4% of theory,

Melting point: 297-300 ⁰ C 'Calc .: C 51.86 H 4.35 N 16.13 S 9.23

F .: 51.58 4.54 16.10 9.15

j5 7

7- (2-Methoxy-4-methylsulfonyloxyphenyl) -1H-iraidazo [1,2-a] [1,3,5] triazin-2-one

Prepared from 2-amino-4-hydroxy- [1,3,5] triazine and α-bromo 2'-methoxy-4-methylsulfonyloxy-acetophenone analogously to Example Yield: 17.5% of theory, melting point: 258-261 ⁰ C

Calc .: C 44.06 H 3.98 N 15.81 S 9.14 Gef --.-: - - ~ 43- _r .8-6- ... _'.- 3, 9 3 15, 64 .9,21

_Be_i_s_p_i_el__5_8

7- (2-Methoxy-4-methylsulfonylphenyl) -1H, 3H-imidazo [1,2-a] [1,3,5] triazine-2,4-dione

Prepared from 6-amino-1H, 3H- [1,3,5] triazine-2,4-dione and α-bromo-2-methoxy-4-methylsulfonyl-.acetophenone analogously to Example 1.

Yield: 22% of theory, melting point:> 300 ° C

Calc .: C 46.42 H 3.59 N 16.66 Vessel: 46.38 3.71 16.78 Mass spectrum: M ⁺ = 336 m / e.

J! · $. 'Jr. Jp-EiJrJ--

7- (2-Methoxy-4-methylsulfonyloxyphenyl) -1H, 3H-imidazo * [1,2-a] [1,3,5] triazine-2,4-dione

Prepared from 6-amino-1H, 3H- [1,3,5] triazine-2,4-dione and

α-bromo-2-methoxy-4-methylsulfonyloxy-acetophenone analog

Example 1. ·

Yield: 22% of theory, Melting point:> 300 ⁰ C O Calc .: 44.32 H 3.43 N 15.90 Found .: 44.51 3.55 15.68 Mass Spectrum: M = '352 m / e ,

Example 60

7- (2-Methoxy-4-dimethylaminosulphonyl-phenyl) -IH, 3H-imidazo [1,2-a] - [- I, 3, S] -triazine-2, 4-dione

Prepared from 6-amino-1H, 3H- [1,3,5] triazine-2,4-dione and α-bromo-2-methoxy-4-dimethylaminosulfonyl-acetophenone analog

Example 1. '

Yield: 12% of theory, Melting point:> 300 ⁰ C Rf value: 0.6 (silica gel, eluent: methylene chloride / methanol = 10: 2)

UV spectrum (ethanol): 300-320 nm (0.075)

Example 61

2- (2-Methoxy-4-methylsulfonylphenyl) -7H-imidazo [1,2-a] pyrazine-8-one

Prepared from 3-amino-1H-pyrazine-2-one and α-bromo-2-methoxy-4-methylsulfonyl-acetophenone analogously to Example Yield: 56% of theory, melting point: 283-286 ° C. (dec.). , ·

- 44 _BeJ._s_p_i_e_l__6_2

2- (2-Methoxy-4-methylsulfonyloxyphenyl) -7H-imidazo [1,2-a] pyrazine-8-one

Prepared from 3-amino-1H-pyrazine-2-one and α-bromo-2-methoxy-4-methylsulfonyloxy-acetophenone analogously to Example 1.

Yield: 43% of theory,

Melting point: 273-275 ° C

Calc .: C 50.11 H '3.91 N 12.5.2 S 9.55 F .: 49.80. 3.9-9 12.82 9.61

2- (2-naphthyl) -7H-imidazo [l, 2-a] pyrazin-8-one

Prepared from 3-amino-1H-pyrazine-2-one and 2- (2-bromoacetyl) naphthalene analogously to Example 1.

Yield: 47% def theory,

Melting point:> 300 ^° C.

Calc .: C 75.55 H 4.24 N 16.08

Gef .:. 75,17 4,14 15,83

6- (4-Hydroxy-2-methoxy-phenyl) -2-methyl-mercapto-IH-imidazo [2,1-f] [1,2,4] triazin-4-one. '

Prepared from 6- (2-methoxy-4-hydroxyphenyl) -2,4-bis-methylmercapto-imidazo [2,1-f] [1,2,4] triazine and concentrated hydrochloric acid analogously to Example 4.

I - 7 O

Yield: 28.1% of theory, melting point: 307-309 ° C. Calc .: C 51.32 H 3.98 N 18.41 S 10.52

Gef .: 51.21 4,10 18,15 10,85

jBe_ispJ._el_ _6_5 2- (1-Methoxy-naphth-4-yl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from α-bromo-4- (1-methoxy) -acetonaphthone and 2-amino-4-hydroxy-pyrimidine analogously to Example Yield: 15%. of theory, Melting point: 300-301 ⁰ C (decomp.) Calc .: C 70.09 H 4.50 N 14.42 Found .: 69.87 4.49 14.31

J_e_i_s_pJ._el_ _6_6 2- (2-methoxy-naphth-6-yl) -6H-imidazo [1,2-c] pyrimidin-5-one

Prepared from α-bromo-6- (2-methoxy) -acetonaphthone and 2-hydroxy-4-amino-pyrimidine analogously to Example Yield: 15.3% of theory, melting point:> 300 ^° C. Calc .: C 70.09 H 4,50 N 14,42 Found: 70,29 4,62 14,54

_Be_i_sp_i_e_l_ _6_7 2- {1-Methoxy-naphth-2-yl) _ -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from l-bromo-2- (1-methoxy) -acetonaphthone and

2 - "" Amino-4-hydroxy-pyr imidine analogously to Example 1. Yield: 3.1% of theory, Melting point: 215-216 ⁰ C.

Calc .: C 70.09 'H 4.50 N '14, 43' Gef.: 70.06. 4,39 14,11

68

2- (naphth-2-yl) -8H-imidazo [1,2-a] pyrimidin-7-one

Prepared from α-bromo-2-acetonaphthone and • 2-amino-4-hydroxy-pyrimidine analogously to Example 1.

Yield: 11% of theory, melting point:> 250 ^° C.

Ber .:. C 73.55 H 4.24 N 16.08 Gef.: 73.26 4.30 15.82

2- (4-Amino-2-methoxy-5'-phidyl) -5H-imidazo [1,2-b] pyridazin-6-one

1.7 g (5.36 mmol) of 2- (4-acetamino-2-methoxyphenyl) -6-chloroimidazo [1,2-b] pyridazine are refluxed for 32 hours in 150 ml of 4N potassium hydroxide solution. After cooling and filtration, it is adjusted to pH 6.5 with glacial acetic acid. The resulting precipitate is filtered off, washed with water and dried in a vacuum oven over phosphorus pentoxide. Yield: 84% of theory, Melting point: 243-250 ⁰ C (decomp.) Calc .: C 60.93 H 4.72 N 21.86 Found .: 60.76 4.67 20.50

6 "~> ^Η · ft", ^f / · u J ι

2- (2-Methoxy-4-sulfamoyl-phenyl) -5H-imidazo [1,2-b] pyridazine-6-oti. '

Prepared from 6-chloro-2- (2-methoxy-4-sulfamyl-phenyl) -imidazo [1,2-b] pyridazine and 4N potassium hydroxide analog Example Yield: 38% of theory,

Melting point: 297-300 ⁰ C (-Zers.) Calcd .: C, '46, 15 H 4.17 N 16.56 S 9.48

Gef .: 46.36 4.09 16.70 9.99

Mass spectrum: M ⁺ - = 320 m / e.

2- (2-Methoxy-4-methylsulfonamido-phenyl) -5H-imidazo [1,2-b] pyr-idazin-6-one

Prepared from 6-chloro-2- (2-methoxy-4-methylsulfonamidophenyl) -imidazo [1,2-b] pyridazine and 4n potassium hydroxide analog

Example 4.

Yield: 64% of theory,

Melting point: 303-305 ⁰ C (decomp.) Calc .: C 50.29 H 4.22 N 16.76 S 9.59 Found .: 50.29 4.09 16.81 9.81

_Be_isp_ie_l_J7_2

2- (2-methoxy-4-methyl-su, ifyloxyphenyl) -6H-imidazo [1,2-d '. [1,2,4] triazin-5-one

336 mg (3 mmol) of 5-amino-2H-l, 2,4-triazin-3-one are dissolved in

  -_. - /> J if J - 48 -

Suspended 20 ml of absolute dimethylformamide is then added 1.14 g (3.5 mmol) of (j- ^ -bromo - ^ - methoxy - ^ - methylsulfonyloxy-acetophenone mixture is then heated for 2 hours at 12O ⁰ C with stirring. " the yellow suspension is transformed into a clear orange-red solution, the reaction solution is stirred into 100 ml of ice-water, the initially viscous oil is slowly crystallized, the crystalline crude product is filtered off with suction and then once more from ethanol / dimethylformamide (3: 1) with addition recrystallized from charcoal. = 'Yield:' 145 mg (14.3% of theory),

Melting point: 262-264 ° C (dec.) _:

Ber. C 46.44 H 3.60. , N 16.66 S 9.54 Found: 46.45. 3.72 16.70 9.50

Example 73

2- (4-dimethylaminosulphonyl-2-methoxyphenyl) -5H-imidazo [1,2-b] pyridazin-6-one

Prepared from 6-chloro-2- (4-dimethylaminosulphonyl-2-methoxyphenyl) -imidazo [1,2-b] pyridazine and 4n potassium hydroxide analog

Example 4.

Yield: 49% of theory,

Melting point: 285-287 ° C (decomp.)

Calc .: C 51.71 H 4.63 N 16.08 S 9.20 F .: 51.48 4.71 16.17 x 9.44

The following compounds are obtained analogously to the above examples:

2- (4-aminocarbonyl-phenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

7- (4-Methylaminocarbonylphenyl) -1H-imidazo [1,2-a] [1,3,5] tr'iazine-2-one

2- (2-Methoxy-4-methylsulfonylphenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

2- (2,4-dimethoxy-5-dimethylaminosulphonyl-phenyl) -6H-imidazo [1,2-c] pyrimidin-5-one

2- (2-M-ethoxy-4-methylsulfonyloxyphenyl) -1H-imidazo [1,2-c] pyrimidin-7-one

2- (2-Methoxy-4-methylsulfonyloxyphenyl) -5H-imidazo [1,2-b] pyridazin-6-one

2- (4-Methylsulphonamide »-phenyl) -5H-imidazo [1,2-b] pyridazine-6-

2- (4-Amino-phenyl) -5H-imidazo [l, 2-b] pyridazin-6-one

6 ~ (2-Methoxy-4-methylsulfonyloxyphenyl) -lH-imidazo [2, l-f] - [1, 2, 4] triazin-2-one

6- (4-Methylsulfonyloxyphenyl) -1H-imidazo [2,1-fJ [1,2,4] triazin-2-one

6- (2-methoxy-4-sulfamyl-phenyl) -IH- imidazo [2,1-f] [I ₇ 2.4] -tr i a i ζ η - 2 - ο η

  6- (2-Methoxy-4-methylaminosulfonylphenyl) -1H-imidazo [2,1-f] [1,2,4] triazin-2-one

6- (2-methoxy-4-dimethylamine-sulfonyl-phenyl) -IH-imidazo [2,1-f] [1,2,4] triazin-2-one

6- (2-Methoxy-4-methylmercapto-phenyl) -IH-imidazo [2, 1-f] - [1,2,4] triazin-2-one

6- (2-Methoxy-4-methylsulfinylphenyl) -1H-imidazo [2,1-f] - [1,2,4] triazin-2-one

6- (2-methoxy-4-methylsulfonyl-phenyl) -lH-imidazo [2, l-f] - [1,2,4] triazin-2-one

6- (4-Benzyloxy-2-met-hoxyphenyl) -2-methyl thypeto -3H-imidazo [2,1-f] [1,2,4] triazin-4-one

6- (4-Benzyloxy-2-methoxyphenyl) -1H, 3H-imidazo [2, 1-f] [1,2,4] triazine-2,4-dione

6- (4-Hydroxy-2-methoxy-phenyl) -3H-imidazo [2,1-f] [1,2,4] triazin-4-one

6- (2-Methoxy-4-methylsulfonyloxy-phenyl) -3H-imidazo [2,1-f] - [1,2,4] triazin-4-one

6- (4-Hydroxy-2-methoxy-phenyl) -IH, 3H-imidazo [2,1-f] [1,2,4] triazine-2,4-dione

6- (2-Methoxy-4-methylsulfonyloxyphenyl) -1H, 3H-imidazo [2 _/ lf] [1,2,4] triazine-2,4-dione

2- (2-methoxy-4-methylsulfonyloxy-phenyl) -7H-imidazo [1,2-d] - [1,2,4] triazin-8-one

2- (4-Methylsulfonyloxyphenyl) -7H-imidazo [1,2-d] [1,2,4] triazin-8-one

2- (2-Methoxy-4-sulfamoyl-phenyl) -7H-imidazo [1,2-d] [1,2,4] triazine-8-one

2- (2-Methoxy-4-methyl-amino-sulfonyl-phenyl) -7H-imidazo [1,2-d] [1,2,4] triazine-8-one

2- (2-Methoxy-4-dimethylaminosulfonylphenyl) -7H-imidazo [1,2-d] [1,2,4] triazin-8-one.

2 - (2-TMethoxy-4-methylmeraphtho-phenyl) -7H-imidazo [1,2-d] - [1,2,4] triazin-8-one

2- (2-Methoxy-4-methylsulfinylphenyl) -7H-imidazo [1,2-d] - [1, 2,4] triazine-8-one

2- (2-Methoxy-4-methylsulfonylphenyl) -7H-imidazo [1,2-d] - [1,2,4] triazine-8-one

2- (2-methoxy-4-sulfamyl-phenyl) -6H-imidazo [1,2-d] [1,2,4] triazin-5-one

2- (2-methoxy-4-methylaminosulphonyl-phenyl) -GH-imidazo [1,2-d] [1,2,4] triazin-5-one

2- (2-Methoxy-4-dimethylaminosulfonyl-phenyl) -OH-imidazo [1,2-d] [1,2,4] triazin-5-one

2- (2-Methoxy-4-methylmercapto-phenyl] -6H-imidazo [1,2-d] [1,2,4] triazin-5-one

2- (2-Methoxy-4-methylsulfinyl-phen-yl) -6H-iridazo [1,2-d] [1,2,4] triazin-5-one

2- (2-Me thoxy-4-methylsulfonylphenyl) -6H-imidazo [1,2-d] [1,2,4] triazin-5-one

, '·. "... ·. Oi 7.0

2- (2-Methoxy-4-methylsulfonamido-phenyl) -7H-imidazo [1,2-a] pyrazine-8-one

2- (2-methoxy-4-dimethylaminosulfonyl-phenyl) -7H-imidazo [1,2-a] pyrazin-8-one

2- (2-methoxy-4-methylsulfonyloxy-phenyl) -6H, 8H-imidazo [l, 2-a] pyrimidine-5,7-dione

2- (2-methoxy-4-methylsulfonyl-phenyl) -6H, 8H-imidazo [1,2-a] pyrimidine-5,7-dione

2- (2-Methoxy-4-methylsulfonamido-phenyl) -6H, 8H-imidazo [1,2-a] pyrimidine-5,7-dione

2- (2-Methoxy-4-dimethylaminosulfonyl-phenyl) -6H, 8H-imidazo [1,2-a] pyrimidic-5> 7-dione

6- (2-methoxy-4-methylsulfonyloxyphenyl) -1H, 3H-imidazof2, 1-f] [1,2,4] triazine-2,4-dione '

6- (2-methoxy-4-methylsuIfonyl-phenyl) -IH, 3H-imidazo [2,1-f] - [1,2,4] triazine-2,4-dione

& - (2-methoxy-4-methylsulfofamido-phenyl) -lH, 3H-imidazo [2, l-f] [1,2,4] triazine-2,4-dione

6- (2-Methylthoxy-4-d imidyl 1-amino-sulfonyl-phenyl) -H-H-imidazo [2,1-f] [1,2,4] triazine-2,4- dion

.7- (2-Me-thoxy-4-yme-lyso If o-amido-phenyl) -lH, 3H-imidazo [l, 2-a] [1,3,5] triazine-2,4-dione

2- (4-methoxy-phenyl) -6H, 8H-imidazo [l, 2-a] pyrimidine-5,7-dione

2- (4-Methylsulfonamido-phenyl) -6H, 8H-imidazo [1,2-a] pyrimidine-5,7-dione

6- (4-methoxy-phenyl) -lH, 3H-imidazo [2, l-f] [1,2,4] triazine-2,4-dione

6- (4-Methylsulfonyloxy-phenyl) -IH, 3H-imidazo [2,1-f] [1,2,4] triazine-2,4-dione

- 54. -. Example A

Tablets to give 100 mg of 7- (4-methoxy-phenyl) -IH, 3H-imidazo · [1,2-a] [1,3,5] triazine-2,4-dione ·

Composition 1 tablet contains:

Active substance 100.0 mg

Lactose 50.0 mg

Polyvinylpyrrolidone 5.0 mg

Carboxymethylcellulose. 19.0 mg

Magnesium stearate ' 1.0 mg

"175.0 mg"

Wet sieving: 1.5 mm

Drying: circulating air drying cabinet 50 ⁰ C dry sieving: 1 mm.

Mix the remaining excipients with the granules and compress the final mixture into tablets. Tablet weight: 175 mg Stamp:. 8 mm

Example B

Dragees to 50 mg of 7- (4-methoxyphenyl) -IH, 3H-imidazo [1,2-a] [1.3. 5] triazine-2, 4-dione.

Composition:

1'Drage core contains:

Active substance 50.0 mg

Corn starch drink. 20.0 mg

Soluble starch 2.0 mg

Carboxymethylcellulose 7.0 mg

Magnesium stearate 1.0 mg

.80.0 mg

Evenly moisten active substance and starch with aqueous solution of the soluble starch.

Wet sieving: 1.0 mm

Dry Sifting: '1.0 mm,

Drying: 5O ⁰ C in a circulating oven

Mix granules and remaining excipients and seeds

compress.

Core weight: 80 mg

Stamp: 6 mm

Buckling radius: 5 mm *

The finished cores are provided in the usual way with a sugar coating in the coating pan. Dragee weight: 120 mg

Example C

Suppositories to 75 mg 7- (4-methoxy-phenyl) -IH, 3H-imidazo [1,2-a] [1,3,5] triazine-2,4-dione

1 suppository contains:

Active substance 75.0 mg

Suppository mass (e.g., Witepsol H 19

and Witepsol W 45) 1 6 25.0 mg

1 700.0 mg

Production method:

The suppository mass is melted. At 38 ° C., the ground active substance is homogeneously dispersed in the melt. It is cooled to 35 ° C and poured into pre-cooled suppository molds.

Suppository weight: 1.7 g

- 56 Example D

Vials to 50 mg of 7- (4-methoxyphenyl) -1H, 3H-imidazo [1,2-a] [1,3,5] triazine-2, 4-dione

1 'ampule contains:

Active substance 50.0 mg

Ethoxylated hydroxystearic acid 250.0 mg

1,2-propylene glycol 1000.0 mg

Dest. Water ad 5.0 ml

Production method:

The active substance is dissolved in 1,2-propylene glycol and ethoxylated hydroxystearic acid, then made up to the stated volume with water and filtered under sterile conditions. Filling: in ampoules to 5 ml Sterilization: 20 minutes at 120 ⁰ C.

Example E

Drops to 100 mg of 7- (4-methoxy-phenyl) -IH, 3H-imidazo [1,2-a] [1.3.5] triazine-2,4-dione

W effective substance • 1.0 G Methyl p-oxybenzoate 0,035 G p-Oxybenzoesäurepropylester 0,015 G anisole 0,0 5 g. menthol 0.06 G Sodium saccharine 1.0 G glycerin 10.0 G ethanol ad 40.0 G Dest. Water 100.0 ml

- 57 Method of production:

The benzoic acid esters are dissolved in ethanol and then the anisole and menthol are added. Then the active substance, glycerol and sodium saccharin dissolved in the water is added. The solution is then filtered clear. ,

Claims (10)

Erfindunqsanspruch 1, Process for the preparation of imidazo derivatives of the general formula in the one or two of the radicals A, B, C or D is a nitrogen atom,. another of the radicals A, B _# C or O is a hydroxymethine group and the remaining radicals A, B, C or D are methine groups, one of these methine groups, if it is adjacent to a nitrogen atom, being replaced by a hydroxymethine group or by a methine group substituted by an alkylmercapto group, R ₁ and R - together with two intervening carbon atoms of Phenylririges. an optionally substituted by an alkoxy phenyl ring and - 53- R eiri hydrogen atom or an alkoxy group or one of the radicals R, R_ or R, a hydroxy, phenyl. alkoxy, alkylmercapto, alkylsulfinyl, amino, alkylsulfonyloxy, suifamyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonamido, N-alkyl-alkylsulfonamido, cyano, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group or, if R _? and R ₃ do not simultaneously represent hydrogen atoms or when A ₄ B _s C and D together with the Imidazolririg no Imidazo / ~ l _f 2-b_ / pyridazine-6 (5H) -one j Imidazo / ^ l ^ -c ^ y 'pyrimidin-5 (6H) -one and 5-alkylmercapto-imidazo "" l, 2-c__7 pyrimidin-7 (8H) -ones, also an alkoxy or alkylsulfonyl group, a second of the radicals R ₁ , R ₂ or R _{3 is} a hydrogen atom, a hydroxy or alkoxy group and the last of the radicals R ₁ , R ₂ or R _{3 is} a hydrogen atom or an alkoxy group, it being possible for the alkyl part in all the abovementioned radicals to contain 1 or 2 carbon atoms, their tautomers and their acid addition salts, characterized in that a) a compound of the general formula NH in the A, B, C and D are as defined in items 3 to 7, with a compound of the general formula - c- (/ ^ W ,(in) in the R ₁ , R ₉ and R-. as defined in claims 1 to 7 and X represents a nucleophilic leaving group such as a halogen atom, is reacted or b) for the preparation of compounds der.general formula I, in which one of the radicals Rj, R2 or R ^ is an alkylsulfonyloxy, alkylsulfonamido or N-alkyl-alkylsulfonamido, a compound of the general formula (IV) in the A, B, C and D are as defined in claims 1 to 7 and the radicals R ', R ₉ ¹ and R' with the exception of Alkylsulfonyloxy-, Alkylsulfonamido-. and N-alkyl-alkylsulfonamido group have the meanings mentioned for R-, R ^ or R ^ in claims 1 to 7, but where one of the radicals Rj_ ', R2' or R ^ 'is a hydroxy, amino, methylamino - or ethylamino group, with a compound of the general formula - SO- - Y in the ^; R _{4 is} a methyl or ethyl group and Y is a nucleophilic leaving group such as a halogen atom or an alkoxy group, is reacted or c) for the preparation of compounds of the general formula I in which at least one of the radicals R 1, R 2 or R 3, an _alkoxy, -phenylalkoxy or alkylmercapto group or one of the radicals R-, R ₂ or R ₃ denotes an N-alkyl-alkylsulfonyl represent fonamidogruppe, a compound of the general formula (VI) in the A, B, C and D are as defined in claims 1 to 7 and R ₁ ", R ₂ " and R ₃ ¹ 'have the meanings mentioned for R ₁ , R ₂ or R ₃ in the claims to 7, but wherein at least one of the radicals R ₁ ", R ₂ " or R ₃ "a Hydroxy, mercapto or Alkylsulfonamidogruppe must, with a compound of the general formula , (VII) in the R _{4 is} an alkyl or phenylalkyl group each having 1 or 2 carbon atoms in the alkyl part and Z represents a nucleophilic leaving group such as a halogen atom or a sulfonyloxy group, is alkylated, or d) for the preparation of compounds of general formula I in which one of R ^ / R 2 or R 3 represents an aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulphamyl, alkylaminosulphonyl or dialkylaminosulphonyl group, a compound of the general formula , (VIII) in the A, B, C and D are as defined in claims 1 to 7, R 2 '"and R *, R' 'are the same as R 1, R 2 and R 3 except for. Have aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulphamyl, alkylaminosulphonyl or dialkylaminosulphonyl group as defined in claims 1 to 7, W represents a carbonyl or sulfonyl group and U represents a nucleophilic leaving group such as a halogen atom or an alkoxy group with an amine of the general formula H-N-, (IX)   - if · in the R ₅ and Rg, which may be the same or different, each represents a hydrogen atom, a methyl or ethyl group, is reacted. e) for the preparation of compounds of the general formula I in which the radicals A, B, C and D are as defined above and one of the radicals R-,, R ^ or R-, an amino, hydroxy or · aminocarbonyl group or R 1, R 2 and R 2 are as defined above and at least one of the radicals A, B, C or D represents a hydroxymethine group, a compound of the general formula , Cx). in the R-, R ₂ and R _{3 are} as defined in claims 1 to 7, and. · A ¹ , B ¹ , C and D ^{1 have} the meanings mentioned for A, B, C and D in claims 1 to 7, but either one of the methine groups recited in claims 1 to 7 can be replaced by a hydrolytically removable radical such as is substituted by a halogen atom, an alkoxy or alkylmercapto group or one of the radicals R-,, R2 or R- must represent an alkanoylamino, cyano or alkylsulfonyloxy group, is hydrolyzed or f) for the preparation of compounds of the general formula I in which one or two of the radicals A, B, C or D is a nitrogen atom, another of the radicals A, B, C or D is a hydroxymethine or alkylmercaptomethine group and the rest of the A, B, C or D radicals represent methine groups, one or two radicals of a compound of the general formula , (XI) in the R ₁ R and R- are as defined in items 1 to 7 and dle.-R.es te.-Ä "... _t B", C "and D" have the meanings mentioned for A ₁ B ₁ C and D in points 1 to 7, wherein. However, at least one of the methine groups mentioned in the items 1 to 7 by a reductively cleavable radical 'as must be substituted by a halogen atom or an alkylmercapto, is cleaved reductively and if desired, then a thus-obtained compound of general formula I in which one of the radicals ^R l * ^R 2 or R ₃ represents an amino group, after conversion into the corresponding diazonium salt into a compound of general formula I in which one of the radicals ^R l * ^R 2 ^{0 <} ^ ^{er R} 3 ^{einö represents} cyano group, is converted or a compound of the general formula I thus obtained is converted into its acid addition salt, in particular into its acid addition salt, with a physiologically compatible inorganic or organic acid. 2 · Method according to item 1, characterized in that the reaction is carried out in a solvent. \ u υ u 3. The method according to the points la and 2, characterized in that the reaction at temperatures between O and'150 ⁰ C, preferably at temperatures between 20 and 100 ⁰ C, performed. 4. Process according to points Ib, Ic, Id and 2, characterized in that the reaction is carried out in the presence of an acid-binding agent, 5, method according to the points Ib ₁₁ lc, ld and 2, identified. characterized in that the reaction is carried out at temperatures between 0 and 100 * C, preferably at temperatures between room temperature and 50 G, 6. A process according to the items Ie and 2, characterized in that the hydrolysis is carried out in the presence of an acid or in the presence of a base. , 7 »method according to the items Ie, 2 and 6, characterized in that the reaction at temperatures between. see -10 and 120 C, preferably at temperatures between room temperature and the boiling temperature of the reaction mixture is carried out. 8. The method according to the items Ie and 2, characterized in that the partial hydrolysis is carried out with concentrated sulfuric acid or with an alkali metal hydroxide in the presence of hydrogen peroxide at room temperature. 9. Method according to points If and 2, characterized by the fact that the reductive cleavage is carried out by hydrogenolysis «· · 10. The method according to the items if, 2 and 9, gekannzeichnet in that the reaction at temperatures between -10 and 100 ⁰ C, preferably at temperatures between 0 and 60 C, is performed.