EP0808311A2 - Nouveaux derives de pyridylpiperazine ou de pyridazinylpiperazine, leur procede de production, et medicaments contenant ces composes - Google Patents

Nouveaux derives de pyridylpiperazine ou de pyridazinylpiperazine, leur procede de production, et medicaments contenant ces composes

Info

Publication number
EP0808311A2
EP0808311A2 EP96901794A EP96901794A EP0808311A2 EP 0808311 A2 EP0808311 A2 EP 0808311A2 EP 96901794 A EP96901794 A EP 96901794A EP 96901794 A EP96901794 A EP 96901794A EP 0808311 A2 EP0808311 A2 EP 0808311A2
Authority
EP
European Patent Office
Prior art keywords
group
compounds
general formula
formula
lower alkyl
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.)
Withdrawn
Application number
EP96901794A
Other languages
German (de)
English (en)
Inventor
Christos Tsaklakidis
Alfred Mertens
Gerd Zimmermann
Wolfgang Schäfer
Liesel Dörge
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.)
Roche Diagnostics GmbH
Original Assignee
Roche Diagnostics GmbH
Boehringer Mannheim GmbH
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 Roche Diagnostics GmbH, Boehringer Mannheim GmbH filed Critical Roche Diagnostics GmbH
Publication of EP0808311A2 publication Critical patent/EP0808311A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Definitions

  • the present invention relates to new pyridyl or pyridazinyl piperazine derivatives, processes for their preparation and medicaments which contain these substances.
  • pyridine or pyridazine derivatives which still have a carboxylic acid function effectively inhibit the aggregation of the platelets and can therefore be used for the treatment of diseases which are attributable to thromboembolic events, such as stroke, myocardial infarction or arterial occlusive diseases, as well as inflammation, osteoporosis or tumor diseases
  • the present invention relates to compounds of general formula 1
  • R ' is hydrogen, lower alkylene, lower alkenyl, cycloalkyl, cycloalkylene, an optionally substituted mono- or bicyclic aryl. an optionally substituted hetaryl. an optionally substituted arylalkyl or one of the groups
  • W means nitrogen or ⁇ CR 5 .
  • X. Z independently of one another are nitrogen or ⁇ CH, and in the event that W is a nitrogen atom.
  • X must be the group ⁇ , CH.
  • ⁇ means a valence stitch or the carbonyl group.
  • B is a valence stitch or a C 1 -C 4 alkylene chain which is mono- or polysubstituted or substituted by lower alkyl or an i 0 OR 2 group
  • D represents a valence sting, and for the case that X is a nitrogen atom. can also be the carbonyl group, where A_ B and D must not simultaneously denote the valence stitch.
  • R 2 is hydrogen, lower alkylene or aromatic alkylene.
  • R ⁇ R independently of one another are hydrogen or lower alkyl, or together with the nitrogen atom to which they are attached form a five- to six-membered heterocyclic ring,
  • R ⁇ is hydrogen or a group -OR 2 .
  • lower alkyl is said to be a straight-chain or branched C 1 -C 6 -alkyl group such as, for example, methylene.
  • Ethnic Propyl Isopropyl. Butvl. Isobutvl. Pentyl or hexyl, especially Methvl Ethvl. Represent propyl, isobutvl and pentvl
  • Lower Alkenvl means unsaturated residues with 3-6 carbon atoms such as allyl, but-2-enyl, hexa-2.4-d ⁇ envl. especially allyl
  • Cvcloalkvl means an optionally substituted 3-7-ghed ⁇ gen ring, such as the
  • Cvclopropyl-, Cyclobutvl-. Cyclopentvl-, Cyclohexvl- or the Cycloheptyl ⁇ ng, in particular the Cvclopropvl. Cvclopentvl- and Cyclohexvl ⁇ ng These cycloalkyl residues can be mono- or disubstituted by a C ⁇ -C (j-alkyl group, preferably the Methvl-, ethyl or isopropyl group.
  • Cycloalkenyl means an optionally substituted cyclopentenyl, cyclohexenyl or cycloheptenyl ring. These rings can be mono- or disubstituted by a C 1 -C 4 -alkylene group, preferably the methyl, ethyl or isopropyl group, and also chlorine. Bromine or hvdroxy, methoxy. Benzyloxy, Armno, Methylamino, Dimethylamino or Benzvlamino distr be substituted
  • radicals R- 5 and R together with the nitrogen atom to which they are bound form a heterocvc's ring, it is a saturated or unsaturated 5-6-membered ring, such as the pyrrolidine, pipeline, morphohn, pyrrole -, Pipe ⁇ din-. Morpholinnng
  • the carbocyclic and heterocyclic rings can optionally be one or two by C i -Co alkylene groups. preferably the methyl. Ethyl or isopropyl group, and by chlorine. Bromine or hydroxyl, methoxy, benzyloxy, armno, methylamino, dimethlamino or benzvlamino groups can be substituted
  • Arvl usually means the optionally mono- or polysubstituted phenyl radical.
  • Hetarvi usually means a mono- or polysubstituted Pv ⁇ din-. Py ⁇ dazin-, Pvrrol-. Thiophene. Furan or imidazole
  • Bicvc's Arvl usually means an indane or naphtha radical which may be substituted one or more times. preferably the naphthalene radical aryl. Bicychic aryl and hetaryl radicals can optionally be substituted one or more times by C ⁇ -Co-alkyl groups, preferably the Methvl-. Ethyl or isopropyl group. as well as by chlorine, bromine, fluorine, or hydroxy. Alkoxy such as methoxy, benzyloxy. Acetvloxy, carboxy, ethoxy carbonvl. Aminocarbonyl. Methvlaminocarbonyl-.
  • ⁇ rvlalkvl usually means an unsubstituted or mono- or polysubstituted Benzvl-.
  • Phenethvl- or Phenylpentvlrest come as substituents Ci-Cg-Alkvlrestrest. preferably methyl, ethyl or isopropyl, and chlorine. Bromine.
  • Fluorine or hydroxy, methoxy, benzyloxy, acetyloxy, carboxy, ethoxycarbonyl, aminocarbonyl, methamine laminocarbonyl, dimethylaminocarbonyl, cyano, amino, methylamino, dimethylamino, benzvlamino, acetylamino -, Benzoylamino and amidino groups in question
  • Preferred compounds are compounds of the formula I in which the group ABD represents a group (CH2) ⁇ _3 or CO- (CH2) i-3- and Z, X, W and R 1 have the meaning given - -
  • ring -X W represents a 1 4-Cvclohexvl ⁇ denvl- or 1 4-p ⁇ pe ⁇ d ⁇ nvl-R ⁇ ng and Z.
  • A-B-D- and R ' have the meaning given
  • ABD represents the group ethylene or carbon-vinyl and the ring -X ⁇ ⁇ W- is a 1,4-cyclohexvi ⁇ denyl ring and Z and R 'have the meaning given
  • R 1, A, B, D, W X. and Z have the meanings given above and R ⁇ is a Methvl-, ethyl, tert-Butvl- or benzyl radical, prepared
  • R 1 and R 6 have the meanings given above and L is a leaving group such as, for example, shark or O-SO2-R 7 , where shark is chloride. Bromide or iodide and R 7 methyl. Phenyl, p-methylphenyl or p-nitrophenyl should be implemented.
  • R ', R 6 , XZA B and D have the meanings given above, optionally with an alkylating agent of the general formula VIII.
  • R * - and L have the meanings given above, alkylated.
  • B has the meaning given above and Y and Q independently of one another are hydrogen, the group OR 2 in which R 2 has the meanings indicated above, or a halogen such as chlorine or bromine, with an amine of the general formula XII.
  • A_ B. and L have the meanings given and P denotes a protective group for amines such as acetyl, tert-butyloxycarbonyl, Benzvl or benzyloxycarbonyl, and then the protective group P is removed from the product formed
  • R ⁇ and R 6 have the meanings given above and Ar is an aryl in the sense of the definition given above for aryl, or the ketone of the formula V of a Horner-Em ons reaction with a phosphonoacetic ester of the general formula XX.
  • R 1 and R 6 have the meanings given above, are catalytically hydrogenated and
  • Alcohols of the general formula XVTI are commercially available
  • T ⁇ arvlphosphine of formula XXVI T ⁇ arvlphosphine of formula XXVI.
  • Trialkyl phosphites of the formula XXVII and 4-P ⁇ pe ⁇ don of the formula XXVIII are commercially available
  • hydrolysis of an ester of the general formula II or the formula XXXIII to the corresponding carboxylic acid of the general formula I or XXX is carried out by customary processes, in which a carboxylic acid ester of the general formula II in water or in a mixture of water. Tetrahydrofuran. Dioxane. Methanol or ethanol preferably in a water / tetrahydrofuran mixture with a hydroxide such as sodium. Potassium or lithium hydroxide, preferably sodium or lithium hydroxide, or with an acid such as hydrochloric acid, sulfuric acid or trifluoroacetic acid. preferably trifluoroacetic acid and at temperatures between room temperature and 80 ° C. preferably treated at room temperature
  • Diethyl ether or dimethylformamide preferably dimethylformamide or tetrahydrofuran using a base such as potassium hydride. Sodium hydride. Potassium carbonate or sodium hydrogen carbonate, preferably sodium hydride or potassium carbonate and at temperatures between room temperatures and 180 ° C, preferably at 120 ° C
  • the reaction of a ketone of the general formula V with an ester of the general formula VI or the reaction between 4-piperidone and an ester of the formula VI takes place under the conditions of the aldol reaction. in a solvent such as methanol, ethanol, toluene. Tetrahvdrofuran. Diethyl ether or dimethylformamide.
  • tetrahydrofuran or dimethylformamide using a base such as sodium or potassium methylate or ethylate.
  • a base such as sodium or potassium methylate or ethylate.
  • Potassium hexamethyl disilazide. preferably sodium hydride or lithium diisopropylamide and at temperatures between -78 ° C. and 90 ° C. but preferably at -78 ° C. and room temperature.
  • the protective group P can, if necessary, be removed from compounds which carry the protective group P and which are described or included in this patent specification by a compound carrying the protective group P having aqueous mineral acids or bases. treated as hydrochloric acid, sulfuric acid or trifluoroacetic acid or sodium or potassium hydroxide solution or this catalytic hydrogenation, such as. B. with palladium / carbon hydrogen
  • halogenation of a compound of the general formula VI or the formula XVIII, or of the formula XXIII, or of the formula XXIV, or of the formula XXIX, or of the formula XXX is carried out by reaction with molecular halogen (chlorine, bromine, iodine), preferably bromine without solvent or in an inert solvent such as methylene chloride.
  • molecular halogen chlorine, bromine, iodine
  • compounds of the general formula VI can be halogenated by being treated in an aprotic solvent. solvents such as tetrahydrofuran and at a low temperature, preferably at -78 ° C., with a lithium amide such as lithium diisopropylamide and then the ⁇ -position metalated compounds of the general formula XVI with bromine. Iodine. Carbon tetrachloride or carbon tetrabromide (M Hesse. Helv Chim Acta 72, 847 (1989) RT. Arnold, J Org Chem 43, 3687 (1978)) or with N-chloro- or N-bromosuccinimide (W Oppolzer, Tetrahedron Leu 26. 5037 (1985)
  • Conversion of the hydroxyl group of a compound of general formula XV. XVII, XVIII. XXIII. or XXIX in a sulfonic acid ester is carried out by customary methods, such as, for example, by condensation with a sulfonic acid chloride. like methane. Benzene, p-toluene or p-nitrobenzenesulfonic acid chloride. preferably methane or p-toluenesulfonic acid chloride. in an inert solvent such as methylene chloride. Tetrahydrofuran or diethyl ether. preferably methylene chloride using an auxiliary base such as T ⁇ methvl- or T ⁇ ethytamin or pyridine, preferably Triethvlamin and at a temperature between 0 ° C and room temperature
  • the Wittig reaction between a ketone of the general formula V and a phosphorane of the general formula XIX. or a ketone of formula XXVIII and a phosphorane of formula XIX. or a ketone of the formula XXXV with a phosphorane of the formula XXXVI is carried out according to known processes by refluxing the reactants in an aprotic solvent such as benzene. Toluene or xylene, preferably toluene
  • the Horner-Emmons reaction between a ketone of the general formula V and a phosphonoacetic ester of the general formula XX. or a ketone of the formula XXVIII and a phosphonoacetic ester of the formula XX are usually carried out in a solvent such as dimethylformamide, tetrahydrofuran. Diethyl ether or 1,4-dioxane, preferably dimethylformamide or tetrahydrofuran using a base such as sodium hydride. Butyllithium. Lithiumdiisopropylamid or Nat ⁇ umhexamethyldisilazid. in front- preferably sodium hydride or lithium diisopropylamide and preferably at -78 ° C or 100 ° C at -78 ° C or room temperature.
  • the oxidation of a compound of general formula VI to a compound of general formula XV is generally carried out in a solvent such as tetrahydrofuran by adding a base such as lithium diisopropylamide or lithium N-isopropyl-N-cyclohexvlamide using an oxidizing agent such as an oxaziridine derivative.
  • a base such as lithium diisopropylamide or lithium N-isopropyl-N-cyclohexvlamide
  • an oxidizing agent such as an oxaziridine derivative.
  • reaction between a compound of general formula IV and a compound of general formula XXVII generally takes place without solvent at temperatures between room temperature and 150 ° C., preferably at 130 ° C. with a reaction time between 30 minutes and 30 hours, preferably 18 hours.
  • the reduction of a carboxylic acid of the general formula XXTV or XXX to an .Alcohol of the formula XXIII or XXIX is generally carried out in a solvent such as tetrahydrofuran or diethyl ether with a reducing agent such as lithium aluminum hydride and at a reaction temperature between 0 ° C. and the reflux temperature of the solvent used, preferably carried out at 40 ° C.
  • acylation of an A in the general formula XII or formula XIII. or the formula XXXI with a carboxylic acid derivative of the formula XI, or the formula XXV. or the formula XXXII. or the formula XIV is usually carried out in a solvent like Methvlenchlo ⁇ d. Dimethvlformamid or Pv ⁇ dm preferably Methvlenchlo ⁇ d or Pv ⁇ din with the addition of an auxiliary base such as T ⁇ ethvlamin or 4-D ⁇ methvlam ⁇ nopy ⁇ d ⁇ n and preferably at a temperature between - 10 ° C and 50 ° C at room temperature
  • a ketone of the general formula V is usually carried out in a solvent such as methanoi. Ethanol. Tetrahydrofuran or diethyl ether preferably methanol with a reducing agent such as Nat ⁇ umborhvd ⁇ d, Lithiumborhvd ⁇ d, or Lithiumaluminiumhvd ⁇ d. preferably Nat ⁇ umborhvd ⁇ d and at a temperature between - 10 ° C and - ⁇ -30 ° C, preferably at room temperature
  • a solvent such as methanoi. Ethanol. Tetrahydrofuran or diethyl ether preferably methanol with a reducing agent such as Nat ⁇ umborhvd ⁇ d, Lithiumborhvd ⁇ d, or Lithiumaluminiumhvd ⁇ d. preferably Nat ⁇ umborhvd ⁇ d and at a temperature between - 10 ° C and - ⁇ -30 ° C, preferably at room temperature
  • Alkaline salts are the main pharmacologically acceptable salts.
  • Caustic soda. Potash lye, water ammonia or nurse such as T ⁇ methvl- or T ⁇ ethvlamin.
  • T ⁇ fluoroacetic acid or hydrochloric acid produces The salts are usually cleaned by falling over from water / acetone
  • novel substances of the formula I according to the invention and their salts can be administered enterally or parenterally in liquid or solid form. All customary forms of application are possible here, for example tablets, capsules. Dragees, syrups, solutions, suspensions, etc. Water is preferably used as the injection medium, which contains the additives, such as stabilizers, which are customary for injection solutions. Solution broker and buffer included
  • Such additives are eg tartrate and citrate buffers.
  • Ethanol complexing agents (such as ethylenediaminetetraacetic acid and its non-toxic salts), high-molecular polymers (such as liquid polyethylene oxide) for regulating the viscosity.
  • Liquid carrier substances for injection solutions must be rigid and are preferably filled into ampoules. Solid carrier substances are, for example, strong, lactose. Manrut. Methyl cellulose. Talc, highly disperse silicas, high molecular weight fatty acids (such as stearic acid). Gelatin, agar. Calcium phosphate.
  • Magnesium stearate and vegetable fats, solid high-molecular polymers (ie polyethylene glycols), preparations suitable for oral administration can, if desired, contain flavorings and sweeteners
  • the dosage can depend on various factors, such as the mode of administration. Species. Depend on age and / or individual condition.
  • the daily doses to be administered are about 10-1000 mg / person, preferably 100-500 mg / person and can be taken in one or more times distributed
  • Vacuum off. acidifies the aqueous solution with 1 N hydrochloric acid and extracts it three times with 50 ml of methylene chloride. After drying the combined extracts over sodium sulfate and stripping off the solvent, 13 g of (1,4-dioxa-sp ⁇ ro- [4,5] dec-8-yl) acetic acid FAB are obtained. 200
  • the mixture was dissolved and the solution was mixed with 0 9 g of 10% palladium / carbon.
  • the mixture was then hydrogenated at normal pressure and room temperature for 4 h, and then the
  • the catalyst is evaporated, the filtrate is evaporated to dryness, the residue is taken up in 70 ml of a 1 M hydrofluoric acid / acetonitrile mixture and the reaction solution is stirred for 12 hours at room temperature. The solvent is then evaporated off in vacuo, the residue with 10 ml of saturated sodium Solution added and the aqueous solution thus obtained extracted three times with 10 ml of methylene chloride
  • Microtiter plates are coated overnight with 2 ⁇ g / ml isolated activated GpIIb / IIIa receptor. After removing the unbound receptor by washing several times, the surface of the plates is blocked with 1% casein and washed again. The test substance is added in the required concentrations, and the plates are incubated for 10 minutes under rubble. The natural ligand of the gpIIb / IIIa receptor , Fibrinogen is added.
  • the unbound fibrinogen is removed by washing several times, and the bound fibrinogen is determined by a peroxidase-conjugated, antifibrinogenic monoclonal antibody by measuring the optical density at 405 n in an ELISA device Inhibition of fibrinogen-GpIIb / IIIa interaction results in low optical density.
  • An IC 5 is calculated based on a concentration-response curve
  • the GpIIb / IIIa finbrinogen Elisa is a modification of assays that is described in the following literature

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

Abstract

L'invention concerne des composés de la formule (I), dans laquelle R<1> représente hydrogène, alkyle inférieur, alcényle inférieur, cycloalkyle, cycloalcényle, un aryle monocyclique ou bicyclique éventuellement substitué, un hétaryle éventuellement substitué, un arylalkyle éventuellement substitué ou l'un des groupes -OR<2>, -NR<3>R<4>, W représente azote ou -CR<5>, X, Z représentent, indépendamment l'un de l'autre, azote ou -CH, et lorsque W représente un atome d'azote, X doit représenter le groupe -CH, A représente une liaison de valence ou le groupe carbonyle, B représente une liaison de valence ou une chaîne alkyle C1-C6 éventuellement substituée une fois ou plusieurs fois par alkyle inférieur ou un groupe OR<2>, D représente une liaison de valence, et, lorsque X représente un atome d'azote, peut également être le groupe carbonyle, A, B et D ne pouvant pas représenter simultanément la liaison de valence, R<2> représente hydrogène, alkyle inférieur ou arylalkyle, R<3> et R<4> représentent, indépendamment l'un de l'autre, hydrogène ou alkyle inférieur, ou bien forment un noyau hétérocyclique à cinq ou six chaînons avec l'atome d'azote auquel ils sont liés, R<5> représente hydrogène ou un groupe OR<2>. L'invention concerne également un procédé de production de ces composés, ainsi que des médicaments les contenant, destinés au traitement de maladies imputables à des états thromboemboliques.
EP96901794A 1995-02-10 1996-02-08 Nouveaux derives de pyridylpiperazine ou de pyridazinylpiperazine, leur procede de production, et medicaments contenant ces composes Withdrawn EP0808311A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19504329A DE19504329A1 (de) 1995-02-10 1995-02-10 Neue Pyridyl- bzw. Pyridazinyl-Piperazinderivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
DE19504329 1995-02-10
PCT/EP1996/000524 WO1996024581A2 (fr) 1995-02-10 1996-02-08 Derives de pyridylpiperazine ou de pyridazinylpiperazine, leur procede de production, et medicaments contenant ces composes

Publications (1)

Publication Number Publication Date
EP0808311A2 true EP0808311A2 (fr) 1997-11-26

Family

ID=7753583

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96901794A Withdrawn EP0808311A2 (fr) 1995-02-10 1996-02-08 Nouveaux derives de pyridylpiperazine ou de pyridazinylpiperazine, leur procede de production, et medicaments contenant ces composes

Country Status (9)

Country Link
EP (1) EP0808311A2 (fr)
JP (1) JPH10513465A (fr)
AU (1) AU4622996A (fr)
CA (1) CA2212227A1 (fr)
DE (1) DE19504329A1 (fr)
IL (1) IL117082A (fr)
TW (1) TW408121B (fr)
WO (1) WO1996024581A2 (fr)
ZA (1) ZA961045B (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2155307A1 (fr) * 1993-03-29 1994-10-13 Michael Garth Wayne Composes heterocycliques, inhibiteurs de l'agregation des plaquettes
US5700801A (en) * 1994-12-23 1997-12-23 Karl Thomae, Gmbh Piperazine derivatives, pharmaceutical compositions containing these compounds, their use and processes for preparing them

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9624581A2 *

Also Published As

Publication number Publication date
WO1996024581A2 (fr) 1996-08-15
JPH10513465A (ja) 1998-12-22
CA2212227A1 (fr) 1996-08-15
IL117082A0 (en) 1996-06-18
WO1996024581A3 (fr) 1996-11-28
AU4622996A (en) 1996-08-27
ZA961045B (en) 1997-08-11
DE19504329A1 (de) 1996-08-14
TW408121B (en) 2000-10-11
IL117082A (en) 2000-12-06

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