[go: up one dir, main page]

WO1989002890A1 - Composes de thiohydantoine - Google Patents

Composes de thiohydantoine Download PDF

Info

Publication number
WO1989002890A1
WO1989002890A1 PCT/JP1988/000979 JP8800979W WO8902890A1 WO 1989002890 A1 WO1989002890 A1 WO 1989002890A1 JP 8800979 W JP8800979 W JP 8800979W WO 8902890 A1 WO8902890 A1 WO 8902890A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
lower alkyl
pharmaceutically acceptable
compound
phenyl
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
Application number
PCT/JP1988/000979
Other languages
English (en)
Japanese (ja)
Inventor
Limited Taiho Pharmaceutical Company
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taiho Pharmaceutical Co Ltd
Original Assignee
Taiho 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 Taiho Pharmaceutical Co Ltd filed Critical Taiho Pharmaceutical Co Ltd
Priority to AU24842/88A priority Critical patent/AU2484288A/en
Publication of WO1989002890A1 publication Critical patent/WO1989002890A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to a novel thiohydantoin compound or a pharmaceutically acceptable salt thereof, a pharmacological composition containing the same, and an aldose ⁇ reductase inhibitor.
  • Aldose reductase reduces aldoses such as glucose and galactose to polyols such as sorbitol.
  • the resulting polyol is relatively stable and hardly migrates outside the cell, so it accumulates inside the cell.
  • the activity of aldose * reductase is increased, so that polyols are abnormally accumulated in the lens, nervous tissue, and vascular tissue.
  • the osmotic pressure increases in the cells of these tissues, causing the cells to swell, impairing cell functions, and causing tissue damage.
  • the present inventors have conducted intensive studies in view of the above-mentioned problems of the prior art, and as a result, have found that a novel thiocyanate hydantoin compound represented by the following general formula (I) and a salt thereof are excellent in aldose reductase. It has been found that it has harmful effects and also has an excellent blood glucose lowering effect and lipid lowering effect II, and is useful as a medicament. Thus, the present invention has been completed.
  • the present invention provides a novel thiohydantoin compound represented by the following general formula (I) or a salt thereof which is chemically acceptable. .
  • R s is the same or different and represents a hydrogen atom, a lower alkyl group, a carboxymethyl group, or a halogenobenzyl group. ].
  • the halogen atom defined by R 2 is fluorine, chlorine, bromine, or iodine; and the halogeno-pheno-nole group is hunoleolopheninole, black-hole pheno-nole, or promo-pheno. Phenyl, dichlorophenyl, bromofluorine, etc.
  • Illustrative examples of the radical include a radical.
  • Examples of the lower alkyl group defined by R 2 , R 3 and R include a straight or branched alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.
  • halogenobenzyl group defined by R 3 and Ri examples include halogen atoms such as fluorobenzene, chlorobenzene, and bromobenzene; benzene, dichlorobenzyl, and promofluorobenzyl.
  • -A benzyl group having 1 to 4 substituents on the benzene ring can be exemplified.
  • the present invention includes any geometric isomer of the thiohydantoin compound represented by the formula (I).
  • the salt of the compound of the present invention include alkali metal salts such as sodium, potassium and lithium, alkaline earth metal salts such as calcium and magnesium, ammonium salts, tetramethylammonium, tetraethylammonium, tetrapropyl and the like.
  • Tetraalkylammonium salts such as ammonium and tetraptylammonium, methylamine, ethylamine, isopropylamine, tert-butylaminedimethylamine, getylamine, trimethylamine, Mono- to trialkylamine salts such as triethylamine; cycloalkylamine salts such as cyclopentylamine and cyclohexylamine; phenyl lower alkylamine salts such as benzylamine, phenethylamine phenylpropylamine; 5- to 6-membered heterocyclic compounds containing 1 to 2 nitrogen atoms in the ring structure as hetero atoms such as gin, piperazine, imidazoline, and pyrrole ⁇ , monoethanolamine, monopronophenolamine To triethanolamine, such as triethanolamine, diethanolamine, triethanolamine, etc., organic amine salts such as lysine, arginine, histidine, etc
  • R 1 is a benzoisoxazolyl group, a tetrahydrobenzozo isoxazolyl group or a group (R 2 is
  • R 3 is a hydrogen atom or a halogenobenzyl group
  • R 4 is a carboxymethyl group.
  • Particularly preferred compounds are those in which R i is a group and R 2 is a lower
  • the compound of the present invention represented by the general formula (I) and a pharmaceutically acceptable salt thereof are excellent aldose reductors. It has an inhibitory effect on zeolites, and is particularly useful for chronic symptoms and complications associated with diabetes. Further, the compound of the present invention and a pharmaceutically acceptable salt thereof also have excellent blood glucose lowering action and lipid lowering action.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of the above general formula (I) or a pharmaceutically acceptable salt thereof and an effective amount of a pharmaceutically acceptable carrier, and an inhibitor of Ars-Dactidase. Is provided.
  • the present invention provides a method for inhibiting al'dose ⁇ reductase, which comprises administering to a patient an effective amount of the compound of the general formula (I) or a pharmaceutically acceptable salt thereof. .
  • the thiohydantoin compound represented by the general formula (I) according to the present invention is, for example, an aldehyde derivative represented by the general formula ( ⁇ ) and a thiohydantoin compound represented by the following general formula (I):
  • the above condensation reaction can be carried out under the same conditions as known aldol condensation, Knebenagel condensation reaction, etc., and is carried out in a suitable solvent in the presence of a catalyst.
  • catalysts that can be used in the present condensation reaction include sodium hydroxide, sodium hydroxide, calcium hydroxide, sodium carbonate, sodium hydrogencarbonate, sodium methoxide, sodium ethoxide, sodium acetate, and the like.
  • Organic acid anhydride compounds such as acid and propionic anhydride are used.
  • the proportion of the catalyst to be used can be appropriately selected, but it is usually preferable to use the catalyst in an amount of about 0.1 to 3.0 times the molar amount of the aldehyde derivative (II).
  • the usage ratio of the aldehyde derivative ( ⁇ ) and the thiohydantoin derivative ( ⁇ ) can be selected as appropriate, but the thiohydantoin derivative (m) is usually 1.0 to 2.0 times the aldehyde derivative (E). It is preferable to use about a mole.
  • the reaction is usually carried out with heating, and generally proceeds advantageously at the reflux temperature of the solvent.
  • the solvent for example, alcohols such as methanol, ethanol, propanol and isopropyl alcohol, ethers such as dimethyl ether, dipropyl ether, tetrahydrofuran and dioxane, and organic acids such as acetic acid and propionic acid are used. You.
  • the aldehyde derivative of the general formula ( ⁇ ), which is used as a starting material in the above condensation reaction, is usually a known compound or easily produced by a known method [Gazz. Chim, Italy. )> 73, 99 (1943), Tetrahedron, 23, 4697 (1967)].
  • the thiohydantoin derivative represented by the general formula (M) is also a known compound or is prepared by a known method. Easily manufactured. For example, it can be easily produced according to the method described in Journal of Chemical Society (J. Am. Chem. Soc). 47, 240 (1925).
  • novel thiohydantoin compound of the present invention produced by the above reaction can be easily isolated by ordinary separation means such as recrystallization, column chromatography and the like.
  • the thiohydantoin compound of the present invention can be used in mammals including humans for the purpose of preventing or treating diseases caused by aldose reductase, specifically, diabetic cataract, neuropathy, renal disorder, retinopathy and the like.
  • Pharmaceutical forms for administration may be, for example, any of oral preparations, injections, suppositories, eye drops and the like, and these administration forms can be produced by conventional methods known to those skilled in the art, respectively.
  • an excipient if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, a flavoring agent, etc. are added to the compound of the present invention, and the mixture is treated in a conventional manner. Tablets, coated tablets, granules, powders, capsules and the like can be manufactured. Such additives may be those commonly used in the art, for example, excipients such as lactose, sucrose, sodium chloride, sodium pudose, starch, calcium carbonate, Kaolin, crystalline cellulose, silicic acid, etc.
  • Is dried starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, glyceryl monostearate, lactose, etc., and purified talc, stearate, borax, polyethylene glycol are used as lubricants
  • sucrose, orange peel, citric acid, tartaric acid, and the like can be used as the soothing agent.
  • an oral solution, a syrup, etc. can be produced by a conventional method by adding a flavoring agent, a buffering agent, a stabilizer, a flavoring agent and the like to the compound of the present invention.
  • the amendment may be any of those mentioned above.
  • the impactant include sodium citrate
  • examples of the stabilizer include tragacanth, gum arabic, gelatin, and the like.
  • a pH adjusting agent, a buffer, a stabilizing agent, an isotonic agent, a local anesthetic, etc. are added to the compound of the present invention, and a subcutaneous, intramuscular, or intravenous injection is prepared by a conventional method.
  • examples of the pH adjusting agent and the buffer include sodium quaterate, sodium acetate, and sodium phosphate.
  • Local anesthetics include proforce hydrochloride, lidocaine hydrochloride, and the like.
  • an excipient such as an unsaturated fatty acid triglyceride and, if necessary, a surfactant such as tween are added to the compound of the present invention, and then the compound is prepared by a conventional method. can do.
  • a diluent such as sterile distilled water or physiological saline may be used, and if possible, it may be made isotonic with a pH adjuster, a buffer or the like, and then manufactured in a usual manner.
  • the amount of the compound of the present invention to be incorporated in each of the above-mentioned administration tables is not limited depending on the condition of the patient to which the present invention is applied or the dosage form, but generally, the oral preparation per dosage unit form Then about 1 C! Desirably, the dose should be about 30 mg to about 30 mg, for injection about 10 to 50 mg, for suppositories about 10 to 200 mg, and for eye drops about 5 to 50 fflg.
  • the daily dose of the drug having the above-mentioned dosage form varies depending on the patient's symptoms, weight, age, sex, etc. and cannot be determined unconditionally, but it may be generally about 5 to 90 nig per adult per day. It is preferable to administer once or about 2 to 4 divided doses.
  • the rate of decrease in the absorbance of NADPH due to the reduction of the substrate glyceraldehyde at a wavelength of 34 Onin was determined by measuring with a spectrophotometer according to the method of 25 13 (19776). .
  • the measurement of AR activity was performed as follows. That is, 0.1 M phosphate buffer (pH) was added to the cell on the sample side of the spectrophotometer.
  • AR activity was determined from the rate of change in absorbance per minute in the linear portion of the change in absorbance from 1 minute to 3 minutes after the start of the reaction, and a halo effect curve was created.
  • 50% inhibitory concentration (IC S0) was calculated from the dose-response songs ⁇ .
  • Capsules were produced at the following compounding ratios.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Composés de thiohydantoïne représentés par la formule générale (I), dans laquelle R1 représente un groupe benzisoxazolyle, un groupe tétrahydrobenzisoxazolyle, un groupe styryle, un groupe alpha-méthylstyryle ou (II), R2 représente un atome d'halogène, un groupe alkyle inférieur, un groupe trifluorométhyle, un groupe méthoxy, un groupe phénéthyle, un groupe benzyloxy, un groupe éthoxycarbonyle, un groupe cyclopropyle, un groupe isobutylcyclohexyle, un groupe cyclohexylméthoxy, un groupe phényle, un groupe halogénophényle, un groupe méthoxyphényle, un groupe tétrahydropyranyle, un groupe thiényle ou un groupe pyridinyle, et R3 et R4, qui peuvent être identiques ou différents, représentent chacun un atome d'hydrogène, un groupe alkyle inférieur, un groupe carboxyméthyle ou un groupe halogénobenzyle. On décrit ces composés ainsi que leurs sels acceptables en pharmacologie, une préparation pharmaceutique les contenant en tant qu'ingrédients actifs, de même qu'un inhibiteur d'aldose réductase.
PCT/JP1988/000979 1987-09-29 1988-09-27 Composes de thiohydantoine Ceased WO1989002890A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU24842/88A AU2484288A (en) 1987-09-29 1988-09-27 Thiohydantoin compounds

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP62/245591 1987-09-29
JP24559187 1987-09-29
JP63187252A JPH01156965A (ja) 1987-09-29 1988-07-26 チオヒダントイン化合物
JP63/187252880726 1988-07-26

Publications (1)

Publication Number Publication Date
WO1989002890A1 true WO1989002890A1 (fr) 1989-04-06

Family

ID=26504234

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1988/000979 Ceased WO1989002890A1 (fr) 1987-09-29 1988-09-27 Composes de thiohydantoine

Country Status (2)

Country Link
JP (1) JPH01156965A (fr)
WO (1) WO1989002890A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0718290A1 (fr) * 1994-12-20 1996-06-26 Nippon Zoki Pharmaceutical Co., Ltd. Dérivés carboxyalcoyle hétérocycliques
US5681843A (en) * 1994-12-20 1997-10-28 Nippon Zoki Pharmaceutical Co., Ltd. Parabanic acid derivatives
US6040326A (en) * 1996-12-27 2000-03-21 Nippon Zoki Pharmaceuticals Co., Ltd. 3-deoxyglucosone production inhibitor
US6197806B1 (en) 1995-12-20 2001-03-06 Nippon Zoki Pharmaceutical Co., Ltd. Eliminating agent for activated oxygen and free radicals
US6251929B1 (en) 1998-11-16 2001-06-26 Nippon Zoki Pharmaceuticals Co., Ltd. Therapeutic agent for intractable vasculitis
US6451831B1 (en) 2001-02-13 2002-09-17 Nippon Zoki Pharmaceutical Co., Ltd. Agent for hypoalbuminaemia
WO2011075784A1 (fr) * 2009-12-23 2011-06-30 Peter Maccallum Cancer Institute Composés, leurs préparations et leurs utilisations

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2835545B2 (ja) * 1990-11-27 1998-12-14 株式会社大塚製薬工場 白内障予防及び治療剤
JP2835547B2 (ja) * 1991-12-25 1998-12-14 株式会社大塚製薬工場 糖尿病治療剤

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0102026A2 (fr) * 1982-08-20 1984-03-07 Hoechst Uk Limited Dérivés du thiazole

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0102026A2 (fr) * 1982-08-20 1984-03-07 Hoechst Uk Limited Dérivés du thiazole

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0718290A1 (fr) * 1994-12-20 1996-06-26 Nippon Zoki Pharmaceutical Co., Ltd. Dérivés carboxyalcoyle hétérocycliques
US5681843A (en) * 1994-12-20 1997-10-28 Nippon Zoki Pharmaceutical Co., Ltd. Parabanic acid derivatives
US5912261A (en) * 1994-12-20 1999-06-15 Nippon Zoki Pharmaceutical Co., Ltd. Carboxyalkyl heterocyclic derivatives
US6197806B1 (en) 1995-12-20 2001-03-06 Nippon Zoki Pharmaceutical Co., Ltd. Eliminating agent for activated oxygen and free radicals
US6040326A (en) * 1996-12-27 2000-03-21 Nippon Zoki Pharmaceuticals Co., Ltd. 3-deoxyglucosone production inhibitor
US6251929B1 (en) 1998-11-16 2001-06-26 Nippon Zoki Pharmaceuticals Co., Ltd. Therapeutic agent for intractable vasculitis
US6451831B1 (en) 2001-02-13 2002-09-17 Nippon Zoki Pharmaceutical Co., Ltd. Agent for hypoalbuminaemia
WO2011075784A1 (fr) * 2009-12-23 2011-06-30 Peter Maccallum Cancer Institute Composés, leurs préparations et leurs utilisations

Also Published As

Publication number Publication date
JPH01156965A (ja) 1989-06-20

Similar Documents

Publication Publication Date Title
KR950011120B1 (ko) 리폭시게나제 억제 화합물 및 이를 함유하는 약제학적 조성물
JP2004359676A (ja) 置換チアゾリジンジオン誘導体
EP0028833A2 (fr) Dérivés de l'imidazole, leur préparation et leur utilisation
JP3053490B2 (ja) チアゾリジン−２，４−ジオン誘導体とその塩及び製造法
EP0030861A2 (fr) Acides isoquinoléine acétiques et compositions pharmaceutiques les contenant
WO1989002890A1 (fr) Composes de thiohydantoine
DK158460B (da) Analogifremgangsmaade til fremstilling af substituerede oxocarboxylsyrer
CA1117944A (fr) Procedes de preparation de nouvelles piperazines disubstituees
FR2610932A1 (fr) Nouvel acide piperazinecarboxylique, sa preparation et son utilisation comme medicament
US5681843A (en) Parabanic acid derivatives
JPS58198467A (ja) 新規プロスタグランデイン誘導体類
US5912261A (en) Carboxyalkyl heterocyclic derivatives
CH633541A5 (en) Pharmacologically active substituted 1,2,4-triazines and medicaments containing these triazines
JPS6399057A (ja) グリシン誘導体
JPS61275274A (ja) １，３−ジチオ−ル−２−イリデン誘導体及びその用途
EP0005091B1 (fr) Nouvelles pipérazines monosubstituées, leurs procédés de préparation et les compositions pharmaceutiques les renfermant
JPH07309852A (ja) 新規チアゾリジンジオン化合物
JP3195455B2 (ja) キノリン−３−酢酸誘導体、その製造法と用途
FR2605008A1 (fr) Derives d'imidazo (4,5-b)pyridinone-2, leur preparation et leur application en therapeutique
JPH04270273A (ja) チアゾリジン−２，４−ジオン誘導体とその塩及びその製造法
JPH062748B2 (ja) 新規ヒダントイン誘導体及び該化合物を有効成分として含有する医薬組成物
NO153572B (no) Analogifremgangsmaate ved fremstilling av terapeutisk aktive 5-(2-(2,3-dihydro-1,4-benzodioxan-2-ylmethyl)-amino)-1-hydroxyethyl)-2-hydroxybenzoesyre-derivater.
US4228166A (en) 2-Keto-4,5-dihydro-3 (2H)-pyridazinones, and their use in treating muscle tension
JPH072776A (ja) アンジオテンシンｉｉ拮抗性ピリジン誘導体
JPH0455191B2 (fr)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU KR US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE

WA Withdrawal of international application
122 Ep: pct application non-entry in european phase