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WO1991009030A1 - 4,5-diphenyle-imidazoles substituees en position 2 - Google Patents

4,5-diphenyle-imidazoles substituees en position 2

Info

Publication number
WO1991009030A1
WO1991009030A1 PCT/EP1990/002147 EP9002147W WO9109030A1 WO 1991009030 A1 WO1991009030 A1 WO 1991009030A1 EP 9002147 W EP9002147 W EP 9002147W WO 9109030 A1 WO9109030 A1 WO 9109030A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
formula
symbols
atom
carbon atoms
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/EP1990/002147
Other languages
English (en)
Inventor
Andrew William Bridge
Neil Victor Harris
David John Lythgoe
Christopher Smith
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.)
Rhone Poulenc Sante SA
Original Assignee
Rhone Poulenc Sante SA
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
Priority claimed from GB898928028A external-priority patent/GB8928028D0/en
Priority claimed from GB909000698A external-priority patent/GB9000698D0/en
Priority claimed from GB909000697A external-priority patent/GB9000697D0/en
Application filed by Rhone Poulenc Sante SA filed Critical Rhone Poulenc Sante SA
Priority to JP91502395A priority Critical patent/JPH05502235A/ja
Publication of WO1991009030A1 publication Critical patent/WO1991009030A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D233/84—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D413/10—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 aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention relates to therapeutically useful imidazole derivatives, to processes for their
  • the present invention provides compounds of the general formula:-
  • R and R 1 are the same or different and each represents a hydrogen or halogen atom or a straight- or branched-chain alkyl group containing from 1 to about 5 carbon atoms
  • W represents a methylene group or a straight alkylene chain containing from 2 to about 5 carbon atoms and is optionally substituted with one or more straight- or branched-chain alkyl groups containing from 1 to about 4 carbon atoms
  • Y represents a group of formula (II),
  • R 4 represents a hydrogen atom or a straight- or branched- chain alkyl group containing from 1 to about 4 carbon atoms
  • the symbols R 4 each represent a hydrogen atom or else together the two symbols R 4 and the carbon atom to which they are both joined form a carbonyl group
  • R 5 represents a hydrogen atom or a hydroxy group
  • Z represents an oxygen or sulphur atom or a group of formula [C(R 3 ) 2 ] q or NR 3
  • m represents zero or an integer from 1 to about 5
  • n represents zero or an integer from 1 to about 5
  • ACAT acyl coenzyme-A:- cholesterol-O-acyl transferase
  • the invention also provides a method for the treatment of a human or animal patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of acyl coenzyme-A:- cholesterol-O-acyl transferase, such as
  • Atherosclerosis hyperlipidaemia
  • cholesterol ester storage disease or atheroma in vein grafts, which comprises administering to the patient an effective amount of a compound of formula (I), or a
  • the invention also provides a compound of formula (I), or a pharmaceutically acceptable acid addition salt thereof, as hereinbefore defined, for use in a new method of treatment, of the human or animal body, by therapy, of conditions which can be
  • acyl coenzyme-A:cholesterol-O-acyl transferase such as atherosclerosis, hyperlipidaemia, cholesterol ester storage disease or atheroma in vein grafts.
  • the present invention also provides
  • the present invention also provides new
  • R and R 1 are the same or different and each represents a hydrogen or halogen atom or a
  • W represents a methylene group or a straight alkylene chain containing from 2 to 4 carbon atoms
  • Y represents a group of formula (V), as
  • R 3 are the same or different and each represents a hydrogen atom or a straight- or branched-chain alkyl group containing from
  • R 4 represent hydrogen atoms and Z represents an oxygen atom or a group of formula [C(R 3 ) 2 ] q , wherein q
  • compositions could be useful as inhibitors of acyl coenzyme-A: cholesterol-O-acyl transferase or in the treatment of conditions such as atherosclerosis, hyperlipidaemia, cholesterol ester storage disease and atherrma in vein grafts.
  • acyl coenzyme-A cholesterol-O-acyl transferase
  • R represents a hydrogen or chlorine atom or a methyl group
  • R 1 represents a hydrogen or chlorine atom or a methyl group
  • W represents a methylene group or an alkylene chain of 2, 3 or 4 carbon atoms
  • Y represents a phthalimido group or an optionally substituted maleimido, pyrrolidinyl, piperidyl, perhydroazepinyl, piperazinyl, or morpholino group;
  • R 3 represents a hydrogen atom or a methyl or ethyl group
  • Important compounds according to the present invention include:
  • the codes 1A to 4B are allocated to compounds for easy reference later in the specification.
  • microsomes prepared from the livers of rats fed a diet
  • radiolabelled oleoyl-CoA in the presence of compounds according to the invention at a concentration of 0.5, 1 or 10 ⁇ g/ml.
  • concentration of 0.5, 1 or 10 ⁇ g/ml The degree of ACAT inhibition produced is shown in Table I.
  • the compounds according to the invention inhibited increases in plasma cholesterol concentrations, measured after 3 days, relative to control animals fed on the cholesterol supplemented diet without the drug, by amounts as shown, for example, in Table II.
  • [DPIM] is as hereinbefore defined and M is an alkali metal, preferably a sodium or potassium, atom, with a compound of the general formula:-
  • X is a group displaceable by a thiolate salt, such as a halogen, e.g. a chlorine, atom or an alkyl- or aryl-sulphonyloxy group (e.g. methanesulphonyloxy or 4-toluene- sulphonyloxy) and W and Y are as hereinbefore defined.
  • a thiolate salt such as a halogen, e.g. a chlorine, atom or an alkyl- or aryl-sulphonyloxy group (e.g. methanesulphonyloxy or 4-toluene- sulphonyloxy) and W and Y are as hereinbefore defined.
  • a thiolate salt such as a halogen, e.g. a chlorine, atom or an alkyl- or aryl-sulphonyloxy group (e.g. methanesulphonyloxy or 4-toluene-
  • a proton acceptor which may be organic, such as an amine (e.g. triethylamine), or inorganic, such as a carbonate of an alkali metal (e.g. potassium carbonate).
  • a proton acceptor such as organic, such as an amine (e.g. triethylamine), or inorganic, such as a carbonate of an alkali metal (e.g. potassium carbonate).
  • reaction is generally carried out in an inert organic solvent, for example xylene, and optionally in the presence of an acidic catalyst, such as 4-toluenesulphonic acid, at the reflux temperature, with azeotropic removal of water.
  • an inert organic solvent for example xylene
  • an acidic catalyst such as 4-toluenesulphonic acid
  • the starting materials and intermediates can be prepared by the application or adaptation of known methods.
  • compounds of formula (VII) can be prepared by the reaction of a base such as sodium hydride with compounds of the general formula:-
  • Compounds of formula (IX) can also be prepared by the reaction of compounds of formula (I), wherein Y represents a phthalimido group, with hydrazine, in a solvent such as ethanol at temperatures up to reflux.
  • salts as used in this specification is meant acid addition salts the anions of which are relatively innocuous to the animal organism when used in
  • pharmaceuticals may be selected from salts derived from inorganic acids, for example hydrochlorides,
  • hydrobromides hydrobromides, phosphates, sulphates and nitrates, and organic acids, for example oxalates, lactates,
  • acid addition salts of compounds of formula (I) are prepared by reaction of the parent compounds of formula (I) with the appropriate acid, by the application or adaptation of known methods.
  • salts of compounds of formula (I) are useful for the purposes of purification of the parent
  • the parent compounds of formula (I) can be regenerated from their salts by the application or adaptation of known methods.
  • parent compounds of general formula (I) can be regenerated from their acid addition salts by treatment with an alkali, e.g. aqueous sodium bicarbonate solution or aqueous ammonia solution.
  • alkali e.g. aqueous sodium bicarbonate solution or aqueous ammonia solution.
  • reference to compounds of formula (I) is intended to include reference to their pharmaceutically acceptable acid addition salts, where the context so permits.
  • Acetyl chloride (20ml) was added dropwise to cold (10oC) ethanol (90ml) with stirring, maintaining the temperature below 30°C. After stirring for 0.5hr, a solution of N-[2-(4,5-diphenylimidazol-2-ylthio)- ethyl]morpholine (1.5g, 4.1mmol) in ethanol (10ml) was added and stirring continued for 0.5hr. The mixture was then evaporated and the residue recrystallised from ethanol to give N-[2-(4,5-diphenylimidazol-2-ylthio)- ethyl]morpholine dihydrochloride (1.46g), as a
  • Acetyl chloride 25ml was added dropwise to cold ( ⁇ 10oC) ethanol (70ml) with stirring, maintaining the temperature below 10°C.
  • a solution of N-[3-(4,5-diphenylimidazol-2-ylthio)- propyl]piperidine (3.98g) in ethanol (10ml) was added and stirring continued for 0.5hr.
  • the mixture was then evaporated and the residue crystallised from ethanol / ether to give N-[3-(4,5-diphenylimidazol-2-ylthio)- propyl]piperidine dihydrochloride (2.62g), as a
  • N-[2-(4,5-diphenylimidazol-2-ylthio)ethyl]phthalimide (5.05g), as a very pale cream solid, m.p. 165-166oC;
  • Diglycolic anhydride (8.34g, 32.3mmol) was added to boiling xylene (500ml) with stirring.
  • the iodomethyllactam starting materials were prepared by the method of S. Knapp et al,
  • N-[4-(4,5-Diphenylimidazol-2-ylthio)butyl]- phthalimide (10.2g, 22.5mmol) [prepared as in Example 1(iii)] was heated under reflux in a mixture of ethanol (250ml) and hydrazine hydrate (1.25g, 25mmol) for 22hr. An aqueous solution of hydrochloric acid (2N; 50ml) was then added and boiling continued for 0.5hr. The mixture was then chilled (10°C) and the solid filtered and discarded. The filtrate was evaporated and the residue dissolved in water (250ml) and filtered.
  • Example 2 but using a mixture of cis- and trans-N-(4-chlorobutanoyl)-2,6-dimethylmorpholine as a starting material, there was prepared a nixture of cis- and trans-2,6-dimethyl-N-[4-(4,5-diphenylimidazol-2-yl- thio)butan-1-oyl]morpholine, m.p.147-149°C.
  • compounds of the present invention may be administered parenterally, rectally or orally.
  • Solid compositions for oral administration include compressed tablets, pills, powders and
  • one or more of the active compounds is, or are, admixed with at least one inert diluent such as starch, sucrose or lactose.
  • the compositions may also comprise, as is normal practice, additional substances other than inert diluents, e.g. lubricating agents, such as magnesium stearate.
  • Liquid compositions for oral administration include pharmaceutically acceptable emulsions,
  • compositions according to the invention for oral administration also include capsules of absorbable material such as gelatin, containing one or more of the active
  • compositions according to the invention for parenteral administration include sterile aqueous, aqueous-organic, and organic solutions, suspensions and emulsions.
  • organic solvents or suspending media are propylene glycol, polyethylene glycol, vegetable oils such as olive oil and injectable organic esters such as ethyl oleate.
  • the compositions may also contain adjuvants such as stabilising, preserving, wetting, emulsifying and dispersing agents. They may be sterilised, for example, by filtration through a bacteria-retaining filter, by incorporation in the compositions of sterilising agents, by irradiation or by heating. They may also be manufactured in the form of sterile solid compositions, which can be dissolved in sterile water or some other sterile injectable medium immediately before use.
  • Solid compositions for rectal administration include suppositories formulated in accordance with known methods and containing at least one compound of formula (I).
  • compositions of the invention may be varied, it being necessary that it should constitute a proportion such that a suitable dosage shall be obtained. Obviously, several unit dosage forms may be administered at about the same time. The dose employed will be determined by the physician, and depends upon the desired
  • the doses are generally from about 0.5 to about 70, preferably about 1 to about 10, mg/kg body weight per day by oral administration.
  • compositions according to the present invention illustrate pharmaceutical compositions according to the present invention.
  • No. 2 size gelatin capsules each containing:- N-[2-(4,5-diphenylimidazol-2-ylthio)ethyl]- morpholine 20 mg lactose 100 mg starch 60 mg dextrin 40 mg magnesium stearate 1 mg were prepared in accordance with the usual procedure.
  • No. 2 size gelatin capsules each containing:- 3,5-dimethyl-N-[3-(4,5-diphenylimidazol-2-ylthio)propyl]piperidine-2,6-dione 20 mg lactose 100 mg starch 60 mg dextrin 40 mg magnesium stearate 1 mg were prepared in accordance with the usual procedure.
  • No. 2 size gelatin capsules each containing:- [3-R,S]-3-[(4,5-diphenylimidazol-2-ylthio)- methyl]-1-methylpiperidine 20 mg lactose 100 mg starch 60 mg dextrin 40 mg magnesium stearate 1 mg were prepared in accordance with the usual procedure.

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

Abstract

Dérivés d'imidazole répondant à la formule (I), dans laquelle [DPIM] représente un groupe de formule (DPIM), où R et R1 représentent hydrogène, halogène ou alkyle, W représente alkylène rectiligne en C¿1-6? éventuellement substitué par alkyle, Y représente un groupe de formule (II), (III), (IV), (V), (VI), et leurs sels, inhibent le coenzyme-A acylique: cholestérol-O-acyl- transférase utile au traitement des troubles tels que l'athérosclérose, l'hyperlipidémie, la polycorie cholestérolique et l'athérome des greffes veineuses.
PCT/EP1990/002147 1989-12-12 1990-12-11 4,5-diphenyle-imidazoles substituees en position 2 Ceased WO1991009030A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP91502395A JPH05502235A (ja) 1989-12-12 1990-12-11 イミダゾール類

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB8928028.3 1989-12-12
GB898928028A GB8928028D0 (en) 1989-12-12 1989-12-12 New use
GB909000698A GB9000698D0 (en) 1990-01-12 1990-01-12 New compositions of matter
GB9000698.2 1990-01-12
GB9000697.4 1990-01-12
GB909000697A GB9000697D0 (en) 1990-01-12 1990-01-12 New compositions of matter

Publications (1)

Publication Number Publication Date
WO1991009030A1 true WO1991009030A1 (fr) 1991-06-27

Family

ID=27264841

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1990/002147 Ceased WO1991009030A1 (fr) 1989-12-12 1990-12-11 4,5-diphenyle-imidazoles substituees en position 2

Country Status (4)

Country Link
EP (1) EP0505481A1 (fr)
JP (1) JPH05502235A (fr)
CA (1) CA2071497A1 (fr)
WO (1) WO1991009030A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992015562A3 (fr) * 1991-03-04 1992-10-29 Eastman Kodak Co Preparation d'alcanamide omega-substitue
WO1993023392A1 (fr) * 1992-05-11 1993-11-25 The Du Pont Merck Pharmaceutical Company Imidazoles lies a des groupes heterocycliques bicycliques et utilises pour le traitement de l'atherosclerose
US5310748A (en) * 1992-05-11 1994-05-10 The Du Pont Merck Pharmaceutical Company Imidazoles for the treatment of atherosclerosis
WO1995014673A1 (fr) * 1993-11-22 1995-06-01 Pharmacia S.P.A. Derives de 4,5-diphenylimidazole, leur preparation et leur utilisation en tant qu'inhibiteur de l'acyl-coenzyme-a: cholesterol-o-acyl-transferase (acat)
FR2751647A1 (fr) * 1996-07-25 1998-01-30 Synthelabo Derives de benzimidazole, leurs preparations et leurs applications en therapeutique
EP0862435A4 (fr) * 1995-11-22 1999-02-03 Merck & Co Inc Inhibiteurs de la farnesyl-proteine transferase

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2933739B2 (ja) * 1990-04-09 1999-08-16 明治製菓株式会社 チアゾールまたはイミダゾール誘導体および抗潰瘍剤

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3323870A1 (de) * 1983-07-02 1985-01-03 A. Nattermann & Cie GmbH, 5000 Köln Neue imidazol-2-ylthioalkansaeuren und ihre derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate
EP0240015A2 (fr) * 1986-04-02 1987-10-07 Otsuka Pharmaceutical Co., Ltd. Dérivés de carbostyrile, procédé pour leur préparation, compositions pharmaceutiques les contenant et leur utilisation
JPS6440467A (en) * 1987-08-04 1989-02-10 Hisamitsu Pharmaceutical Co Novel substituted diphenylimidazole derivative
EP0359197A1 (fr) * 1988-09-14 1990-03-21 The Du Pont Merck Pharmaceutical Company Thioimidazoles diaryl-4,5 substitués 2-antihypercholestérolémiques

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3323870A1 (de) * 1983-07-02 1985-01-03 A. Nattermann & Cie GmbH, 5000 Köln Neue imidazol-2-ylthioalkansaeuren und ihre derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate
EP0240015A2 (fr) * 1986-04-02 1987-10-07 Otsuka Pharmaceutical Co., Ltd. Dérivés de carbostyrile, procédé pour leur préparation, compositions pharmaceutiques les contenant et leur utilisation
JPS6440467A (en) * 1987-08-04 1989-02-10 Hisamitsu Pharmaceutical Co Novel substituted diphenylimidazole derivative
EP0359197A1 (fr) * 1988-09-14 1990-03-21 The Du Pont Merck Pharmaceutical Company Thioimidazoles diaryl-4,5 substitués 2-antihypercholestérolémiques

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts, vol. 111, 1989, (Columbus Ohio, US), M. Tsuji et al: "Preparation of (heterocyclylthio- or -sulfinyl)-diphenylimidazoles as antiulcer and antiinflammatory agents", abstract 97243c ; & JP-A-01-040 467 (AISAMITSU PHARMACEUTICAL CO INC) *
Patent Abstracts of Japan, vol. 12, no. 40, abstract of JP-A-62-187 469 (A), 5 February 1988,(TAISHO PHARMACUT CO LTD) *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992015562A3 (fr) * 1991-03-04 1992-10-29 Eastman Kodak Co Preparation d'alcanamide omega-substitue
WO1993023392A1 (fr) * 1992-05-11 1993-11-25 The Du Pont Merck Pharmaceutical Company Imidazoles lies a des groupes heterocycliques bicycliques et utilises pour le traitement de l'atherosclerose
US5310748A (en) * 1992-05-11 1994-05-10 The Du Pont Merck Pharmaceutical Company Imidazoles for the treatment of atherosclerosis
US5364875A (en) * 1992-05-11 1994-11-15 The Du Pont Merck Pharmaceutical Company Imidazoles linked to bicyclic heterocyclic groups for the treatment of atherosclerosis
WO1995014673A1 (fr) * 1993-11-22 1995-06-01 Pharmacia S.P.A. Derives de 4,5-diphenylimidazole, leur preparation et leur utilisation en tant qu'inhibiteur de l'acyl-coenzyme-a: cholesterol-o-acyl-transferase (acat)
EP0862435A4 (fr) * 1995-11-22 1999-02-03 Merck & Co Inc Inhibiteurs de la farnesyl-proteine transferase
FR2751647A1 (fr) * 1996-07-25 1998-01-30 Synthelabo Derives de benzimidazole, leurs preparations et leurs applications en therapeutique
WO1998004546A1 (fr) * 1996-07-25 1998-02-05 Synthelabo Derives de benzimidazole, leurs preparations et leurs applications en therapeutique

Also Published As

Publication number Publication date
CA2071497A1 (fr) 1991-06-13
EP0505481A1 (fr) 1992-09-30
JPH05502235A (ja) 1993-04-22

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