WO1990001479A1 - 4,5-dihydro-3(2h)-pyridazinones, leur procede de fabrication et leur utilisation - Google Patents

4,5-dihydro-3(2h)-pyridazinones, leur procede de fabrication et leur utilisation Download PDF

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Publication number
WO1990001479A1
WO1990001479A1 PCT/EP1989/000859 EP8900859W WO9001479A1 WO 1990001479 A1 WO1990001479 A1 WO 1990001479A1 EP 8900859 W EP8900859 W EP 8900859W WO 9001479 A1 WO9001479 A1 WO 9001479A1
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Prior art keywords
carbon atoms
alkyl
imidazolyl
radical
alkyl part
Prior art date
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PCT/EP1989/000859
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German (de)
English (en)
Inventor
Gerhard Zoller
Rudi Beyerle
Melitta Just
Helmut Bohn
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Cassella Aktiengesellschaft
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Publication date
Application filed by Cassella Aktiengesellschaft filed Critical Cassella Aktiengesellschaft
Priority to KR1019900700710A priority Critical patent/KR900701777A/ko
Publication of WO1990001479A1 publication Critical patent/WO1990001479A1/fr

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    • 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
    • C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • 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
    • 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
    • C07D417/14—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 three or more hetero rings

Definitions

  • the present invention relates to 4,5-dihydro-3 (2H) pyridazinones of the general formula I.
  • R is hydrogen, alkyl having 1 to 3 carbon atoms or
  • R 1 is a phenyl radical of the formula
  • R 2 pyridyl, thiazolyl, imidazolyl, which has an oxygen, nitrogen or sulfur atom or a sulfinyl or sulfonyl group with the phenyl or
  • Indolylrest are linked, or imidazolyl, the thiazolyl and imidazolyl radicals optionally by alkyl having 1 to 3 carbon atoms, halogen, nitro, amino, alkylcarbonylamino having 1 to 3 carbon atoms in the
  • Alkyl part, mono- or dialkylamino with 1 to 3 carbon atoms per alkyl part or alkoxycarbonylamino with 1 to 3 carbon atoms in the alkyl part may be substituted
  • R 3 is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, hydroxy or
  • Halogen and R 4 is hydrogen, alkyl having 1 to 5 carbon atoms, alkylcarbonyl having 1 to 4 carbon atoms in the alkyl part, phenylcarbonyl, alkoxycarbonyl having 1 to 4 carbon atoms in the alkyl part or phenalkoxycarbonyl having 1 to 4 carbon atoms in the alkyl part
  • R 1 is a phenyl radical
  • R 2 cannot be a pyridyl or imidazolyl radical linked via a nitrogen atom.
  • the invention also relates to processes for the preparation of the compounds of the general formula I and their use as pharmacological active ingredients.
  • R is preferably hydrogen, methyl or hydroxymethyl.
  • the pyridyl, thiazolyl and imidazolyl radicals mentioned in the definition of R 2 can be linked via all ring carbon atoms, imidazolyl radicals also via a ring nitrogen atom.
  • Thiazolyl residues are preferably linked via the 2-position, imidazolyl residues via the 1- or 2-position.
  • the thiazolyl and imidazolyl radicals are preferably unsubstituted or substituted by methyl or nitro.
  • radicals R are 2-pyridyl mercapto or 3-pyridyloxy, 4-pyridylamino, 2-thiazolylmercapto, 5-nitro-thiazol-2-yl-amino, imidazol-1-yl, 1- Methyl-imidazol-2-yl-mercapto, the 1-methyl-imidazol-2-yl-sulfinyl and the 1-methyl-imidazol-2-yl-sulfonyl radical, the 4-pyridylamino radical not being attached to one of R 1 standing phenyl radical can be bound.
  • the R 2 radicals can be linked to all ring carbon atoms of a phenyl radical representing R 1 .
  • R 2 is bound to the 4-position of the phenyl radical.
  • the R 2 radicals on an indolyl radical representing R 1 can be linked to all carbon atoms of the six-membered ring. A linkage at the 5 position is preferred.
  • An indolyl radical representing R 1 can be connected to the pyridazinone via the 2- or the 3-position.
  • the 3-position is preferred.
  • Halogen R 3 preferably denotes fluorine, chlorine or bromine.
  • R 3 and R 4 are preferably hydrogen.
  • the compounds of general formula I are analogous to the preparation of other 4,5-dihydro-3 (2H) -pyridazinones by reacting a carboxylic acid or a carboxylic acid derivative of general formula II
  • R and R 1 have the meanings given above and
  • X represents -COOH, -COCl, -CO-O-CO-R 5 , -COOR 5 or -CN, where R 5 denotes an organic radical
  • the organic radical representing R 5 is preferably a
  • R 4 particularly preferably denotes methyl or ethyl.
  • the hydrazine can also be used in the form of the hydrate or a salt in the presence of a base.
  • reaction is advantageously carried out in the liquid phase, for which the presence of an inert solvent or diluent is generally necessary.
  • Suitable solvents or diluents are e.g. Alcohols, especially those with 1 to 6 carbon atoms, e.g. Methanol, ethanol, i- and n-propanol, i-, sec- and tert-butanol, n-, i-, sec-, tert-pentanol, n-hexanol, cyclopentanol, cyclohexanol; Ethers, especially those with 2 to 8 carbon atoms in the molecule, such as e.g. Diethyl ether, methyl ethyl ether, di-n-propyl ether, di-isopropyl ether,
  • Alcohols especially those with 1 to 6 carbon atoms, e.g. Methanol, ethanol, i- and n-propanol, i-, sec- and tert-butanol, n-, i-, sec-, tert-pentanol
  • (-OCH 2 CH 2 ) p where p is a number, for example from 4 to 10, it being possible for one or more benzene rings to be fused onto the ring; Aza and thia crown ethers (coronand amines and coronand sulfides); Glycols and partially etherified glycols, such as, for example, ethylene glycol, propylene glycol, trimethylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether; aliphatic hydrocarbons, such as gasolines, low and high boiling petroleum ethers; aromatic hydrocarbons such as benzene, toluene, o-, m- and p-xylene, pyridine; halogenated aliphatic or aromatic hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, ethylene chloride, chlorobenzene, dichlorobenzene; Ni
  • reaction of the compounds of general formula II with hydrazine is advantageously carried out at temperatures between room temperature and the boiling point of the solvent or diluent used.
  • the compounds of the general formula II can be prepared by various processes known per se, for example by acylating the compounds R 1 -H with
  • R 1 -CO-CH (R) -CH 2 -COOH can be obtained. This sequence of reactions is described, for example, in J.Org. Chem. 38, 4044 ff., (1973).
  • DE-OS 33 28 286 produce, initially creating compounds of the formula R 1 -CO-CH (R) -CH 2 -Cl, in which the
  • Chlorine e.g. exchanged with NaCN or KCN for CN.
  • R 5 has the meaning given above and R 6 for
  • Alkyl preferably methyl
  • the compounds of the general formula III can easily be prepared from the activated carboxylic acid or the carboxylic acid chloride with secondary amines by methods known from the literature.
  • compounds of the general formula I according to the invention can also be obtained by reacting hydroxy-, amino- or mercapto-substituted phenylpyridazinones with heterocycles which have a leaving group in a nucleophilic substitution reaction.
  • Such heterocycles are, for example, 2-bromopyridine or 5-nitro-2-bromothiazole.
  • the compounds of the general formula I contain basic radicals, they form acid addition salts with acids. Inorganic and organic acids are suitable for the formation of such acid addition salts. Suitable
  • Acids are, for example: hydrogen chloride, hydrogen bromide, naphthalenedisulfonic acids, in particular 1,5-naphthalenedisulfonic acid, phosphoric, nitric, sulfuric, oxalic, milk, wine, vinegar, salicylic, benzoic, ant, propionic, Pivaline, diethyl vinegar, malone, amber, pimeline, fumaric, maleic, apple, sulfamine, phenylpropione, gluconic, ascorbic, isonicotine, methane sulfonic, p-toluenesulfonic, lemon or Adipic acid.
  • Pharmacologically acceptable acid addition salts are preferred.
  • the acid addition salts can be prepared as usual by combining the components, advantageously in a suitable solvent or diluent.
  • the compound of the general formula I is expediently dissolved in an organic solvent and mixed with a solution of the desired acid.
  • the hydrochlorides of the pyridazinones of the general formula I according to the invention can be obtained by dissolving the free compound in alcohol and the alcoholic solution with an equivalent amount of a solution of hydrogen chloride in
  • the 4, 5-dihydro-3 (2H) -pyridazinones of the general formula I and their pharmaceutically acceptable acid addition salts according to the invention can therefore be administered to humans as a remedy on their own, in mixtures with one another or in the form of pharmaceutical preparations which are enteral or parenteral Application allowed ten and as an active ingredient contain an effective dose of at least one compound of general formula I or an acid addition salt thereof, in addition to the usual pharmaceutically acceptable carriers and additives.
  • the remedies can be administered orally, e.g. in the form of pills, tablets, coated tablets, dragees, hard and soft gelatin capsules, granules, solutions, syrups, elixirs, emulsions or suspensions or aerosol mixtures.
  • administration can also be rectal, e.g. in the form of suppositories, or parenterally, e.g. in the form of solutions for injection, or percutaneously, e.g. in the form of ointments or tinctures.
  • the pharmaceutical preparations are made in a manner known per se, e.g. by stretching the active ingredients with pharmaceutically acceptable inorganic and / or organic carriers and / or solvents.
  • the pharmaceutical preparations can also contain two or more compounds of the general formula I or their pharmacologically acceptable acid addition salts.
  • the pharmaceutical preparations normally contain the therapeutically active compounds or the mixture of therapeutically active compounds in a concentration of approximately 0.5 to 90% by weight of the total mixture.
  • the carrier materials can be, for example, natural stone powder, such as talc, clay, kaolin, chalk, synthetic stone powder, such as silicates, silica, sugar, such as invert or grape , Milk, malt, fruit or cane sugar, starch or starch derivatives such as corn starch, potato starch, gelatin.
  • natural stone powder such as talc, clay, kaolin, chalk
  • synthetic stone powder such as silicates, silica
  • sugar such as invert or grape
  • milk, malt, fruit or cane sugar starch or starch derivatives such as corn starch, potato starch, gelatin.
  • carriers for soft gelatin capsules and suppositories are, for example
  • Fats, waxes, paraffins, e.g. Petroleum fractions, natural oils, e.g. Peanut or sesame oil, hardened oils, semi-solid and liquid polyols etc. are suitable.
  • Suitable carriers for the production of solutions and syrups are e.g. Water, alcohols, sucrose, invert sugar, glucose, polyols etc.
  • suitable carriers for the production of injection solutions are Water, alcohols, glycols, glycerin, polyols, vegetable oils etc.
  • the pharmaceutical preparations can also contain additives, such as e.g. Fillers, stretchers, explosives, binders, lubricants, wetting agents, stabilizers, emulsifiers, dispersants, preservatives.
  • additives such as e.g. Fillers, stretchers, explosives, binders, lubricants, wetting agents, stabilizers, emulsifiers, dispersants, preservatives.
  • the daily dosage can be within wide limits, e.g. vary from 0.01 mg / kg body weight to 20 mg / kg body weight and must be adapted to the individual circumstances in each individual case.
  • one more dose is selected in the lower part of the specified dosage range.
  • daily amounts of about 0.01 to 1 mg / kg, preferably about 0.05 to 0.5 mg / kg of body weight, are achieved with intravenous administration deliver effective results.
  • the daily dosage is generally about 0.1 to 5 mg / kg, preferably 0.1 to 2 mg / kg of body weight. It may be necessary to deviate from the quantities mentioned. When administering larger quantities, it is advisable to divide the daily dose into several, for example two or three, partial administrations distributed over the course of the day.
  • the pharmaceutical preparations can also contain one or more other pharmaceutically active substances, for example agents which promote blood circulation, such as dihydroergocristine, nicergoline, buphenine, nicotinic acid and its esters, pyridylcarbinol, bencyclane, cinnarizine, naftidrofuryl, raubasine and vincamine; positively inotropic compounds such as digoxin, acetyldigoxin, metildigoxin and lanato glycosides; Coronary dilators such as carbocromes, dipyridamoles, nifedipines and perhexilines; antianginal compounds such as isosorbide dinitrate, isosorbide mononitrate, glycerol trinitrate, molsidomine and verapamil;
  • agents which promote blood circulation such as dihydroergocristine, nicergoline, buphenine, nicotinic acid and its esters,
  • Metoprolol and Penbutolol and oogen metabolic agents such as Pirilinol contain.
  • Active ingredient (finely ground) 50 mg
  • the 4,5-dihydro-3 (2H) -pyridazinone derivatives according to the invention show a therapeutically particularly valuable combination of antithrombotic, cardiotonic and antianginal effects with low blood pressure reduction even in low doses.
  • Tables 1 to 3 below show the activity data of compounds according to the invention obtained in various in vivo and in vitro tests.
  • the values of the venous thrombosis protection given in Table 1 were determined on the vena cava of the rat according to the method of Kumada et al, (Thrombosis Res. 18, 189-203 (1980)), that of the arterial thrombosis protection on the carotid artery of rabbits a modification (Just, 23rd Angiological Symposium, Kitzbühel, 1988, in press) of Harbauer's method ("Attempts to develop a standardized venous thrombosis model in rabbits", 17th Angiological Symposium in Kitzbühel, 1982).
  • the values of the inhibition of platelet aggregation given in Table 2 were determined on human platelets in vitro according to the method of Born (J. Physiol. 162, 67 P (1962)) using arachidonic acid, thrombin, collagen, PAF (platelet activating factor) and of
  • ADP Adenosine diphosphate
  • Systolic and diastolic blood pressure were measured peripherally in the femoral artery using a Statham pressure transducer.
  • LVEDP left ventricular end-diastolic pressure
  • HF heart rate
  • Ventricle determined as a measure of the contractility of the heart. The results obtained are shown in Table 3.
  • ⁇ Bd change in systolic and diastolic
  • ⁇ LVEDP change in left ventricular end-diastolic pressure

Abstract

Des 4,5-dihydro-3(2H)-pyridazinones de formule générale (I) où R est hydrogène, alkyle avec 1 à 3 atomes de carbone ou hydroxyméthyl et R1 représente un résidu phényle de formule (II), ou bien un résidu indolyle de formule (III), R2 étant pyridyle, thyazolyle, imidazolyle, lié via un atome d'oxygène, d'azote ou de soufre ou bien via un groupe sulfinyle ou sulfonyle avec le résidu phényle ou indolyle, ou imidazolyle, les résidus thiazolyle et imidazolyle pouvant éventuellement être subtitués par un alkyle avec 1 à 3 atomes de carbone, un halogène, nitro, amino, alkylcarbonylamino, avec 1 à 3 atomes de carbone dans la partie alkyl, mono- ou dialkylamino avec 1 à 3 atomes de carbone par partie alkyle ou encore alkoxycarbonylamino avec 1 à 3 atomes de carbone dans la partie alkyle, R3 étant hydrogène, alkyle avec 1 à 4 atomes de carbone, alkoxy avec 1 à 4 atomes de carbone, hydroxy ou halogène, et R4 étant hydrogène, alkyle avec 1 à 5 atomes de carbone, alkylcarbonyle avec 1 à 4 atomes de carbone dans la partie alkyle, phénylcarbonyle, alkoxycarbonyle avec 1 à 4 atomes de carbone dans la partie alkyle ou bien phénalkoxycarbonyle avec 1 à 4 atomes de carbone dans la partie alkyle, ainsi que leurs sels d'addition d'acide productibles et convenant à l'usage pharmaceutique, dans lesquels lorsque R1 est un résidu phényl, R2 ne peut être un résidu pyridyle ou imidazolyle lié via un atome d'azote, sont des principes actifs pharmacologiques très utiles.
PCT/EP1989/000859 1988-08-06 1989-07-21 4,5-dihydro-3(2h)-pyridazinones, leur procede de fabrication et leur utilisation WO1990001479A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1019900700710A KR900701777A (ko) 1988-08-06 1989-07-21 4,5-디히드로-3(2h)-피리다지논, 이의 제법 및 이의 용도

Applications Claiming Priority (2)

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DEP3826855.8 1988-08-06
DE3826855A DE3826855A1 (de) 1988-08-06 1988-08-06 4,5-dihydro-3(2h)-pyridazinone, verfahren zu ihrer herstellung und ihre verwendung

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KR (1) KR900701777A (fr)
DE (1) DE3826855A1 (fr)
ES (1) ES2017032A6 (fr)
WO (1) WO1990001479A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8207168B2 (en) 2006-07-25 2012-06-26 Cephalon, Inc. Pyridazinone derivatives
CN105324376A (zh) * 2013-06-27 2016-02-10 辉瑞大药厂 杂芳族化合物及其作为多巴胺d1配体的用途

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110117257B (zh) * 2018-02-05 2022-12-06 安徽省新星药物开发有限责任公司 一种含胍基的p2y12受体拮抗剂、制备方法及其用途

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EP0075436A1 (fr) * 1981-09-17 1983-03-30 Warner-Lambert Company 4,5-Dihydro-6-phenyl substitué-3(2H) pyridazinones substituées et 6-Phenylsubstitué-3(2H)-pyridazinones
EP0090978A2 (fr) * 1982-04-02 1983-10-12 A. Nattermann & Cie. GmbH Imidazolylphényl-tétrahydropyridazines, procédé de leur préparation et compositions pharmaceutiques les contenant
EP0201988A2 (fr) * 1985-03-12 1986-11-20 Smith Kline & French Laboratories Limited Dérivés de dihydropyridazinone
EP0223937A1 (fr) * 1985-09-05 1987-06-03 Roche Diagnostics GmbH Indoles substituées par des hétérocycles, leurs intermédiaires, leur procédé de préparation et médicaments
US4717730A (en) * 1982-12-03 1988-01-05 Warner-Lambert Company 4,5-dihydro-6-(substituted)phenyl-5-methyl-3-(2H)-pyridazinones and pharmaceutical compositions containing the compounds as active components
EP0145019B1 (fr) * 1983-12-14 1990-11-07 Mitsubishi Kasei Corporation Dérivés de pyridazinone et leurs sels

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0075436A1 (fr) * 1981-09-17 1983-03-30 Warner-Lambert Company 4,5-Dihydro-6-phenyl substitué-3(2H) pyridazinones substituées et 6-Phenylsubstitué-3(2H)-pyridazinones
EP0090978A2 (fr) * 1982-04-02 1983-10-12 A. Nattermann & Cie. GmbH Imidazolylphényl-tétrahydropyridazines, procédé de leur préparation et compositions pharmaceutiques les contenant
US4717730A (en) * 1982-12-03 1988-01-05 Warner-Lambert Company 4,5-dihydro-6-(substituted)phenyl-5-methyl-3-(2H)-pyridazinones and pharmaceutical compositions containing the compounds as active components
EP0145019B1 (fr) * 1983-12-14 1990-11-07 Mitsubishi Kasei Corporation Dérivés de pyridazinone et leurs sels
EP0201988A2 (fr) * 1985-03-12 1986-11-20 Smith Kline & French Laboratories Limited Dérivés de dihydropyridazinone
EP0223937A1 (fr) * 1985-09-05 1987-06-03 Roche Diagnostics GmbH Indoles substituées par des hétérocycles, leurs intermédiaires, leur procédé de préparation et médicaments

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8207168B2 (en) 2006-07-25 2012-06-26 Cephalon, Inc. Pyridazinone derivatives
US8247414B2 (en) 2006-07-25 2012-08-21 Cephalon, Inc. Pyridizinone derivatives and the use thereof as H3 inhibitors
US8586588B2 (en) 2006-07-25 2013-11-19 Cephalon, Inc. Aryl pyridazinone derivatives and their use as H3 receptor ligands
US8673916B2 (en) 2006-07-25 2014-03-18 Cephalon, Inc. Methods of treating disorders mediated by histamine H3 receptors using pyridazinone derivatives
CN105324376A (zh) * 2013-06-27 2016-02-10 辉瑞大药厂 杂芳族化合物及其作为多巴胺d1配体的用途

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DE3826855A1 (de) 1990-02-15
ES2017032A6 (es) 1990-12-16

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