WO1994012476A1 - Derive de benzanilide - Google Patents

Derive de benzanilide Download PDF

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Publication number
WO1994012476A1
WO1994012476A1 PCT/JP1993/001691 JP9301691W WO9412476A1 WO 1994012476 A1 WO1994012476 A1 WO 1994012476A1 JP 9301691 W JP9301691 W JP 9301691W WO 9412476 A1 WO9412476 A1 WO 9412476A1
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WO
WIPO (PCT)
Prior art keywords
group
acid
compound
benzanilide
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/JP1993/001691
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English (en)
Japanese (ja)
Inventor
Kazumi Kikuchi
Akihiro Tanaka
Akira Matsuhisa
Yuzo Matsumoto
Ken-Ichiro Sakamoto
Takeyuki Yatsu
Isao Yanagisawa
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Yamanouchi Pharmaceutical Co Ltd
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Yamanouchi Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yamanouchi Pharmaceutical Co Ltd filed Critical Yamanouchi Pharmaceutical Co Ltd
Priority to AU55338/94A priority Critical patent/AU5533894A/en
Publication of WO1994012476A1 publication Critical patent/WO1994012476A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/16—Benzazepines; Hydrogenated benzazepines

Definitions

  • the present invention relates to novel benzoanilide derivatives useful as medicaments, particularly arginine vasopressin antagonists, and pharmaceutically acceptable salts thereof.
  • Arginine vasopressin is a peptide composed of nine amino acids that are biosynthesized and secreted by the hypothalamus-pituitary system.
  • a peptide vasopressin antagonist for example, see JP-A-2-32098
  • a non-beptidic vasopressin antagonist for example, JP-A-3-173877
  • No. 0 and International Publication No. 9-1Z055549 pan fret see 1991
  • the compounds of the present invention differ in structure from these compounds. This is a new compound. Disclosure of the invention
  • the present inventors have conducted intensive studies on compounds having an arginine vasopressin antagonistic activity. As a result, a benzodilide derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof was converted to an arginine vasopressin receptor. The present inventors have found that they have an excellent antagonistic effect on the present invention, and have completed the present invention.
  • R represents a lower alkyl group which may be substituted with a halogen atom, a hydroxyl group, a lower alkoxy group, a nitro group, an amino group, a mono- or di-lower alkylamino group, or a lower alkanoylamino group. Do).
  • the compound of the present invention has a chemical structural characteristic in that it has a biphenyl-2-carboxamide skeleton in which a specific substituent is necessarily substituted on one benzene ring of biphenyl.
  • the term “lower” means a straight or branched carbon chain having 1 to 6 carbon atoms. Therefore, as the “lower alkyl group”, specifically, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl (amyl) group, Isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,2-dimethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group 1,3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutyl group
  • the “lower alkoxy group” includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butyne, pentyloxy (amyloxy), isopentyloxy, and the like.
  • main butoxy group Etokin group, a propoxy group, an isopropoxy group, a C i one c 4 alkoxy groups and butoxy groups, more preferably main butoxy group, an ethoxy group.
  • Specific examples of the "mono- or di-lower alkylamino group” include, for example, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, sec-butylamino group, tert-butylamino group.
  • methyl Mi is a cyano group
  • E Ji Ruami amino group Jimechiruami amino group
  • Jechiruami amino group more favorable Mashiku is Jimechiruamino group.
  • lower alkanoyl group examples include a formyl group, an acetyl group, a pionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, and a hexanoyl group, and an acetyl group is preferable.
  • halogen atoms fluorine, chlorine, bromine
  • the lower alkyl group substituted with a halogen atom include a fluoromethyl group, a chloromethyl group, a difluoromethyl group, a trifluoromethyl group, a trichloromethyl group, a 2,2,2,1-trifluoroethyl group. Among them, a trifluoromethyl group is preferable.
  • the substituent R may be bonded to any position on the benzene ring.
  • the compound of the present invention represented by the general formula (I) may form a salt depending on the type of the substituent.
  • the present invention also includes pharmaceutically acceptable salts of compound (I), such as mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid, formic acid, acetic acid and the like. Acid addition salts with organic acids such as propionic acid, butyric acid, oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, lactic acid, lingic acid, tartaric acid, carbonic acid, glutamic acid, and aspartic acid Is mentioned.
  • mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid, formic acid, acetic acid and the like.
  • Acid addition salts with organic acids such as propionic acid, butyric acid, oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid
  • the compound of the present invention may contain an asymmetric carbon atom depending on the type of the substituent, and the present invention includes a separated form of various optical isomers and a mixture thereof.
  • the compound of the present invention further includes hydrates, various solvates and polymorphs of compound (I) or a salt thereof.
  • R of the compound (I) is an amino group, a mono- or di-lower alkylamino group or a lower alkynylamino group, or a pharmaceutically acceptable salt thereof is preferable.
  • a preferred compound is 2— (4-aminophosphinyl) —4 '-[(2,3,4,5-tetrahydro 1H-1 1-benzazepine-1 1-yl) power ruponyl] benzanilide Or a pharmaceutically acceptable salt thereof.
  • the compound (I) of the present invention can be obtained by converting a substituted biphenylcarbonic acid represented by the general formula (II) or a reactive derivative thereof with an aniline derivative represented by the general formula (III) or a salt thereof by a conventional method.
  • the product can be produced by removing the protecting group if necessary.
  • Derivatives reactive with compound (II) include acid halides such as acid chloride and acid bromide; acid azides; phenolic compounds such as P-ditrophenol, 1-hydroxysuccinimide, and 1-hydroxyl. Active esters obtained by reacting with N-hydroxylamine compounds such as droxybenzotriazole; Symmetric acid anhydrides; Organic acid compounds obtained by reacting with alkyl esters of halocarboxylic acids such as alkyl carbonate halides and bivaloyl halides Mixed acid anhydride or diphenylphospho chloride Mixed acid anhydrides such as phosphoric acid-based mixed acid anhydrides obtained by reacting with phosphoryl and N-methylmorpholine.
  • acid halides such as acid chloride and acid bromide
  • acid azides such as P-ditrophenol, 1-hydroxysuccinimide, and 1-hydroxyl.
  • Active esters obtained by reacting with N-hydroxylamine compounds such as droxybenzotriazole
  • compound (II) when compound (II) is reacted with a free acid or when the reaction is carried out without isolating the active ester, dicyclohexylcarbodiimide, carbonyldiimidazole, diphenylphosphorylazide dimethylphosphoryl cyanide It is preferable to use a condensing agent such as nido
  • the compound of the present invention can be easily produced by the acid halide method.
  • the reaction varies depending on the reactive derivative and the condensing agent used, but is usually halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform, aromatic hydrocarbons such as benzene, toluene, and quinylene, ether, and tetrahydrofuran.
  • halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform
  • aromatic hydrocarbons such as benzene, toluene, and quinylene
  • ether tetrahydrofuran
  • organic solvents inert to the reaction of ethers such as, ethyl esters such as ethyl acetate, N, N-dimethylformamide dimethylsulfoxide, etc., depending on the reactive derivative, under cooling, or under cooling to room temperature It is advantageous to carry out at room temperature or under heating.
  • the compound ( ⁇ ⁇ ) may be used in excess, or N-methylmorpholine, trimethylamine, triethylamine, N, N-dimethylaniline, pyridine, 4- (N, N-dimethylamino) pyridine may be used.
  • N-methylmorpholine trimethylamine, triethylamine, N, N-dimethylaniline, pyridine, 4- (N, N-dimethylamino) pyridine may be used.
  • a base such as pyridine, picolin, lutidine, etc.
  • Pyridines can also be used as solvents.
  • the starting compound (II) has an amino group and a hydroxyl group, and it is necessary to protect it, introduce a protecting group in advance and subject it to this reaction, then remove the protecting group.
  • the removal of the protecting group depends on the type of the protecting group. However, when a substituted or unsubstituted benzyloxycarbonyl group is used as the protecting group for the amino group, catalytic reduction, and in some cases, acid treatment, Other urethane-type protecting groups such as butoxycarbonyl group, alkyl-type protecting groups such as trityl group, and acyl-type protecting groups such as formyl group and acetyl group are acids.
  • a phthaloyl group When a phthaloyl group is used, it can be easily removed by heating with hydrazine.
  • a substituted or unsubstituted benzyl group or benzyloxycarbonyl group is used as the hydroxyl-protecting group, contact-reduction and, in some cases, acid treatment, silyl-based protecting groups such as trialkylsilyl groups can be combined with water. Upon contact, the protecting group of the acyl group can be easily removed by ligating.
  • R 5 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms
  • the lower alkanoylamino-substituted benzonylide derivative represented by the general formula (lb) is composed of the anilinobenzanilide derivative represented by the general formula (la) or a salt thereof and the carboxylic acid represented by the general formula (IV) or a reactive derivative thereof. Can also be produced by reacting
  • the anilinobenzanilide derivative (la) can be produced by reducing the corresponding ditrofulpyl benzoanilide derivative of the general formula (Ic).
  • the reduction is carried out by using a catalyst such as palladium carbon or Raney Nigel in an inert solvent such as alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and dioxane, acetic acid, N, N-dimethylformamide and the like. It is advantageous to carry out the catalytic reduction.
  • a catalyst such as palladium carbon or Raney Nigel in an inert solvent such as alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and dioxane, acetic acid, N, N-dimethylformamide and the like. It is advantageous to carry out the catalytic reduction.
  • Hydroxyphenylpentenzanilide derivatives represented by the general formula (Ie) can be produced by hydrolysis of the corresponding lower alkoxyphenylbenzanilide derivatives.
  • Hydrolysis is carried out by treatment with an acid, a base, and an organometallic reagent.
  • the acid include hydrogen bromide, hydrogen iodide, trifluoroacetic acid, and the like.
  • Pyrididine hydrochloride, aluminum chloride, boron tribromide, boron trichloride, and boron triiodide are used as bases and organometallic reagents such as lithium biphenyl, sodium-liquid ammonia, sodium-pyridine, Examples include lithium iodide-collidine, lithium biphenyl phosphido tetrahydrofuran, sodium thiolate N, and N-dimethylformamide. Among them, three types which can be carried out under mild conditions from room temperature to cooling. Acid hydrolysis with boron bromide or the like is preferred.
  • the compound (I) of the present invention can also be produced by amidating benzazepine and a 4′-carboxybenzanilide derivative in the same manner as in the first production method.
  • Compounds in which R is a mono- or dialkylamino group can also be produced by N-alkylation of the corresponding amino compound by a conventional method.
  • the salt of the compound of the present invention can be easily produced by subjecting it to a usual salt formation reaction.
  • the compound of the present invention thus produced is isolated and purified by commonly used separation operations such as extraction, concentration, distillation, crystallization, recrystallization, filtration, and various types of chromatography. .
  • Industrial applicability such as extraction, concentration, distillation, crystallization, recrystallization, filtration, and various types of chromatography.
  • the pharmaceutically acceptable salts of compound (I) of the present invention and pharmaceutically acceptable salts thereof are based on arginine vasopressin's V1 and V2 receptor antagonism, aquaretic action, urea excretion promoting action, and inhibition of factor VIII secretion.
  • vasodilatory action cardiac stimulatory action, mesangial cell contraction inhibitory action, mesangial cell proliferation inhibitory action, hepatic gluconeogenesis inhibitory action, platelet aggregation inhibitory action, aldosterone secretion inhibitory action, endoserine production inhibitory action, central It has blood pressure regulating action, renin secretion regulating action, memory regulating action, body temperature regulating action, prostaglandin production regulating action, etc., aquaretic agent, urea excretion enhancer, vasodilator, antihypertensive, anti-heart failure agent, anti-renal It is useful as an insufficiency agent, an anticoagulant, etc .; heart failure, hyposodiumemia, vasopressin dysfunction syndrome (SIADH), hypertension, renal failure, edema , Ascites, cirrhosis of the liver, It is effective for prevention and treatment of hypokalemia, water metabolism disorder, diabetes, various ischemic diseases, circulatory
  • V V j receptor binding assay
  • the incubation solution was aspirated using a cell harvester and passed through a glass filter (GF / B) to remove free ligand and excess buffer, and the labeled ligand bound to the receptor was trapped in the glass filter. After removing the glass filter and drying it sufficiently, it was mixed with a liquid scintillation cocktail, and the amount of [H] 3 -vasopressin bound to the membrane was measured with a liquid scintillation counter.
  • IC 5Q is determined from the concentration of the test reagent at which the inhibition rate calculated above is 50%.
  • the binding affinity of the non-radioactive ligand, that is, the dissociation constant (Ki) was calculated from the following equation.
  • Ki dissociation constant
  • V 2 Recep coater Vine ⁇ queuing mediation Si V 2 receptor binding assay
  • the compound of the present invention is superior to the compound described in WO9105548 Shows efficacy.
  • compounds of this in Example 10 was about 3-fold with VI receptor antagonism as compared to the control compound (1), from about 180 fold little gas in V 2 receptor ⁇ anti activity And a control compound currently being developed as an arginine vasopressin receptor antagonist (2) Compared with OPC-31260, it is approximately 70-fold more potent in VI receptor antagonism and approximately 240 in V2 receptor antagonism. It is twice as potent and has been confirmed to have excellent arginine vasopressin receptor antagonistic activity.
  • Formulations containing one or more of the compound (I) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient can be prepared using carriers, excipients and other additives usually used in the preparation of pharmaceuticals. It is prepared by
  • Pharmaceutical carriers and excipients may be either solid or liquid, such as lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic, olive oil, sesame oil, potash oil, and the like. , Ethylene glycol, etc. and other commonly used ones.
  • Administration can be either oral, such as tablets, pills, capsules, granules, powders, and liquids, or parenteral, such as injections such as intravenous and intramuscular injections, suppositories, and transdermals. You may.
  • the dose is determined as appropriate depending on the individual case, taking into account the symptoms, age and sex of the subject, but for oral administration, 0.1 to 50 Omg is usually given once or several times. The dose is divided and administered.
  • 4'12-Trobiphenyl-2-ylcarboxylic acid 50 Omg of acetic acid: N, N-dimethylformamide (1: 1) To a mixed solvent of 2 Om1 was added 10% palladium-carbon 10 Omg, After reducing by 1 ⁇ atmospheric pressure at room temperature, 0.9 ml of a 35% aqueous solution of formaldehyde was added, and the mixture was subjected to atmospheric pressure reduction at room temperature for 2 hours. The insolubles were filtered off, the filtrate was concentrated and azeotroped with toluene to give 4 '-(N, N-dimethylamino) biphenyl-2-ylcarboxylic acid quantitatively as an oil.
  • the extract was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the precipitated crystals were collected by filtration, washed with hexane, and dried under reduced pressure to obtain 888 mg of 4'-methoxybiphenyl-2-ylcarboxylic acid. As obtained.
  • a catalytic amount of N, N-dimethylformamide and oxalyl chloride 270 / z 1 was added to a solution of 502 mg of 4'-nitrobiphenyl-2-ylcarboxylic acid in 2 OmI of methylene chloride under ice cooling, and the mixture was cooled to room temperature. After stirring for 6 hours at, the solvent was distilled off under reduced pressure.
  • the extract was washed successively with 1N aqueous sodium hydroxide solution and 1N hydrochloric acid, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne un dérivé de benzanilide de formule (I) ou un sel pharmaceutiquement acceptable de ce dernier, utile pour traiter l'insuffisance cardiaque, l'hyponatrémie, le syndrome d'antidiurèse inappropriée (SIADH), l'hypertension, l'insuffisance rénale, l'÷dème, les dérèglements du métabolisme de l'eau et autres troubles du même type ou l'antagonisme du récepteur arginine-vasopressine. Dans la formule R représente alkyle inférieur, hydroxy, alcoxy inférieur, nitro, amino, mono- ou di(alkyle inférieur) amino, ou alcanoylamino inférieur facultativement halogénés.
PCT/JP1993/001691 1992-11-25 1993-11-18 Derive de benzanilide Ceased WO1994012476A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU55338/94A AU5533894A (en) 1992-11-25 1993-11-18 Benzanilide derivative

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP33794192 1992-11-25
JP4/337941 1992-11-25

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WO1994012476A1 true WO1994012476A1 (fr) 1994-06-09

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WO (1) WO1994012476A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5521173A (en) * 1995-01-17 1996-05-28 American Home Products Corporation Tricyclic benzazepine vasopressin antagonists
US5532235A (en) * 1995-01-17 1996-07-02 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5536718A (en) * 1995-01-17 1996-07-16 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5654297A (en) * 1995-01-17 1997-08-05 American Cyanamid Company Tricyclic thieno-azepine vasopressin antagonists
US5700796A (en) * 1995-01-17 1997-12-23 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5753648A (en) * 1995-01-17 1998-05-19 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5849735A (en) * 1995-01-17 1998-12-15 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5880122A (en) * 1996-11-01 1999-03-09 American Home Products Corporation 3-Carboxamide derivatives of 5H-pyrrolo 2,1-c! 1,4!-benzodiazepines
WO2001029005A1 (fr) * 1999-10-20 2001-04-26 Ferring Bv Agonistes de la vasopressine bicyclique
WO2001049682A1 (fr) * 2000-01-05 2001-07-12 Ferring Bv Azepines condensees en tant qu'agonistes de vasopressine
US6900200B2 (en) 2001-04-12 2005-05-31 Wyeth Tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
US6977254B2 (en) 2001-04-12 2005-12-20 Wyeth Hydroxy cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US7022699B2 (en) 2001-04-12 2006-04-04 Wyeth Cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators
US7064120B2 (en) 2001-04-12 2006-06-20 Wyeth Tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
US7109193B2 (en) 2001-04-12 2006-09-19 Wyeth Tricyclic diazepines tocolytic oxytocin receptor antagonists
US7202239B2 (en) 2001-04-12 2007-04-10 Wyeth Cyclohexylphenyl carboxamides tocolytic oxytocin receptor antagonists
US7326700B2 (en) 2001-04-12 2008-02-05 Wyeth Cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
CN116920863A (zh) * 2023-06-15 2023-10-24 江苏万盛大伟化学有限公司 一种钒镍镁三元催化剂及其制备方法和应用

Citations (2)

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WO1991005549A1 (fr) * 1989-10-20 1991-05-02 Otsuka Pharmaceutical Co., Ltd. Composes benzoheterocycliques
JPH04321669A (ja) * 1991-04-19 1992-11-11 Otsuka Pharmaceut Co Ltd バソプレシン拮抗剤

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991005549A1 (fr) * 1989-10-20 1991-05-02 Otsuka Pharmaceutical Co., Ltd. Composes benzoheterocycliques
JPH04321669A (ja) * 1991-04-19 1992-11-11 Otsuka Pharmaceut Co Ltd バソプレシン拮抗剤

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CHEMICAL ABSTRACTS, Abstract No. 119 (21): 217053e, (1993). *
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Summaries of the Discussion on Natural Organic Compounds, the 33rd, 228-235, (1991). *

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5521173A (en) * 1995-01-17 1996-05-28 American Home Products Corporation Tricyclic benzazepine vasopressin antagonists
US5532235A (en) * 1995-01-17 1996-07-02 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5536718A (en) * 1995-01-17 1996-07-16 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5610156A (en) * 1995-01-17 1997-03-11 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5612334A (en) * 1995-01-17 1997-03-18 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5654297A (en) * 1995-01-17 1997-08-05 American Cyanamid Company Tricyclic thieno-azepine vasopressin antagonists
US5696112A (en) * 1995-01-17 1997-12-09 American Cyanamid Company Fused heterocyclic azepines as vasopressin antagonists
US5700796A (en) * 1995-01-17 1997-12-23 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5719278A (en) * 1995-01-17 1998-02-17 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5753648A (en) * 1995-01-17 1998-05-19 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5780471A (en) * 1995-01-17 1998-07-14 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5849735A (en) * 1995-01-17 1998-12-15 American Cyanamid Company Tricyclic benzazepine vasopressin antagonists
US5880122A (en) * 1996-11-01 1999-03-09 American Home Products Corporation 3-Carboxamide derivatives of 5H-pyrrolo 2,1-c! 1,4!-benzodiazepines
WO2001029005A1 (fr) * 1999-10-20 2001-04-26 Ferring Bv Agonistes de la vasopressine bicyclique
US6664249B1 (en) 1999-10-20 2003-12-16 Ferring Bv Bicyclic vasopressin agonists
WO2001049682A1 (fr) * 2000-01-05 2001-07-12 Ferring Bv Azepines condensees en tant qu'agonistes de vasopressine
US7560454B2 (en) 2000-01-05 2009-07-14 Vantia Limited Condensed azepines as vasopressin agonists
HRP20020481B1 (hr) * 2000-01-05 2009-03-31 Vantia Limited Kondenzirani azepini kao agonisti vazopresina
US7074781B2 (en) 2000-01-05 2006-07-11 Ferring Bv Condensed azepines as vasopressin agonists
US7064120B2 (en) 2001-04-12 2006-06-20 Wyeth Tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
US7022699B2 (en) 2001-04-12 2006-04-04 Wyeth Cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators
US7109193B2 (en) 2001-04-12 2006-09-19 Wyeth Tricyclic diazepines tocolytic oxytocin receptor antagonists
US7202239B2 (en) 2001-04-12 2007-04-10 Wyeth Cyclohexylphenyl carboxamides tocolytic oxytocin receptor antagonists
US7326700B2 (en) 2001-04-12 2008-02-05 Wyeth Cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US6977254B2 (en) 2001-04-12 2005-12-20 Wyeth Hydroxy cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US6900200B2 (en) 2001-04-12 2005-05-31 Wyeth Tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
CN116920863A (zh) * 2023-06-15 2023-10-24 江苏万盛大伟化学有限公司 一种钒镍镁三元催化剂及其制备方法和应用

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