EP1143944A2 - Utilisation d'arylalcanoylpyridazines - Google Patents

Utilisation d'arylalcanoylpyridazines

Info

Publication number
EP1143944A2
EP1143944A2 EP00916949A EP00916949A EP1143944A2 EP 1143944 A2 EP1143944 A2 EP 1143944A2 EP 00916949 A EP00916949 A EP 00916949A EP 00916949 A EP00916949 A EP 00916949A EP 1143944 A2 EP1143944 A2 EP 1143944A2
Authority
EP
European Patent Office
Prior art keywords
benzoyl
tetrahydro
pyridazine
methoxyphenyl
carbonylamino
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Withdrawn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
EP00916949A
Other languages
German (de)
English (en)
Other versions
EP1143944A3 (fr
Inventor
Jonas Rochus
Michael Wolf
Norbert Beier
Franz-Werner Kluxen
Claus Fittschen
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.)
Merck Patent GmbH
Original Assignee
Merck Patent 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 Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of EP1143944A2 publication Critical patent/EP1143944A2/fr
Publication of EP1143944A3 publication Critical patent/EP1143944A3/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • he invention relates to the use of compounds of the formula I.
  • a and / or OA can be,
  • Q is absent or alkylene with 1-6 C atoms
  • RR 2 each independently of one another -OH, OR 5 , -SR 5 ,
  • R 1 and R 2 together also -0-CH 2 -0-,
  • R and R are each independently A, cycloalkyl with 3-7
  • the invention was based on the task of finding new uses of the compounds of the formula I, in particular those which can lead to the production of medicaments.
  • PDE IV inhibition can e.g. analogous to C.W. Davis in Biochim. biophys. Acta 797, 354-362 (1984).
  • the compounds according to the invention can be used for the treatment of asthmatic diseases.
  • the anti-asthmatic effect of the PDE IV inhibitors is e.g. by T.J. Torphy et al. in Thorax, 46, 512-523 (1991) and can e.g. B. by the method of T. Olson, Acta allergologica 26, 438-447 (1971) can be determined.
  • the inventive compounds can used to treat osteoporosis.
  • the compounds also have an inhibitory effect on the formation of TNF (tumor necrosis factor) and are therefore suitable for the treatment of treatment of allergic and inflammatory diseases, autoimmune diseases and graft rejection reactions.
  • TNF tumor necrosis factor
  • PDE IV inhibitors in the treatment of asthma, inflammatory diseases, diabetes mellitus, atopic dermatitis, psoriasis, AIDS, tumor growth or tumor metastases is e.g. in EP 77
  • the anti-inflammatory effect of the substances according to the invention and their effectiveness for the treatment of e.g. Autoimmune diseases, multiple sclerosis or rheumatoid arthritis can be analogous to the methods of N. Sommer et al., Nature Medicine, 1, 244-248 (1995) or L. Sekut et al., Clin. Exp. Immunol., 100, 126-132 (1995).
  • the compounds of formula I can be used as active pharmaceutical ingredients in human and veterinary medicine. Furthermore, they can be used as intermediates for the production of further active pharmaceutical ingredients.
  • the compounds of formula I can have a chiral center and can therefore occur in several stereoisomeric forms. All of these forms (e.g. R and S forms) and their mixtures (e.g. the R, S forms) are included in Formula I.
  • a and A ' is preferably alkyl, more preferably alkyl substituted by 1 to 5 fluorine and / or chlorine atoms.
  • Alkyl is preferably unbranched and has 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, preferably 1, 2, 3, 4 or 5 carbon atoms and is preferably methyl, ethyl, trifluoromethyl , Pentafluoroethyl or propyl, further preferably isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, but also n-pentyl, neopentyl or isopentyl.
  • Cycloalkyl preferably has 3-7 C atoms and is preferably cyclopropyl and cyclobutyl, further preferably cyclopentyl or cyclohexyl, and also cycloheptyl.
  • Methylene cycloalkyl preferably has 4-8 C atoms and preferably represents methylene cyclopropyl and methylene cyclobutyl, further preferably methylene cyclopentyl and methylene cyclohexyl, and also methylene cycloheptyl.
  • Alkenyl is preferably vinyl, 1- or 2-propenyl, 1-butenyl, isobutenyl, sec-butenyl, further preferred is 1-pentenyl, isopentyl or 1-hexenyl.
  • Alkylene is preferably unbranched and is preferably methylene or ethylene, more preferably propylene or butylene.
  • Shark preferably means F, CI or Br, but also l.
  • the radicals R and R can be the same or different and are in the 3- or 4-position of the phenyl ring. They mean, for example, independently of one another hydroxy, -S-CH 3 , -SO-CH 3 , -S0 2 CH 3 , F, CI, Br or I or together methylenedioxy. However, they are particularly preferably each methoxy, ethoxy, propoxy, cyclopentoxy, or else fluorine, difluoro, trifluoromethoxy, 1-fluorine, 2-fluorine, 1, 2-difluoro, 2,2-difluoro, 1, 2.2-
  • the radical B is preferably 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or
  • the radical B is preferably also methyl, ethyl, propyl, n-butyl, methoxy, ethoxy, propoxy, N-methylamino, N, N-dimethylamino, N-ethylamino or N, N-diethylamino.
  • the invention relates in particular to the use of those compounds of the formula I in which at least one of the radicals mentioned has one of the preferred meanings indicated above.
  • Some preferred groups of compounds can be expressed by the following sub-formulas la to le, which correspond to the formula I and in which the radicals not specified have the meaning given for the formula I, but in which
  • R 1 and R 2 each independently of one another OA, Q methylene and B is pyridinyl, pyrazinyl, pyrimidinyl, thiazo.yl, imidazolyl or isoxazolyl;
  • Ic R 1 and R 2 together are -0-CH 2 -0-, Q is absent or are alkylene with 1-6 C atoms and B are pyridinyl, pyrazinyl, pyrimidinyl, thiazolyl, imidazolyl or isoxazolyl;
  • R 1 and R 2 are each independently OA
  • Q is missing or alkylene with 1-6 C atoms
  • B is A or OA
  • R 1 and R 2 are each independently of one another OA, Q missing or alkylene with 1-6 C atoms,
  • Isoxazolyl, A, OA or NH 2 mean.
  • R 1 , R 2 and Q have the meanings indicated, in particular the preferred meanings indicated.
  • Q is preferably methylene or ethylene, more preferably propylene or butylene.
  • B has the preferred meanings given in the compounds of the formulas III and V, while L means CI, Br, OH or a reactive esterified OH group.
  • L is a reactive esterified OH group, this is preferably alkylsulfonyloxy with 1-6 C atoms (preferably methylsulfonyloxy) or arylsulfonyloxy with 6-10 C atoms (preferably phenyl or p-tolylsulfonyloxy, further also 2- Naphthalenesulfonyloxy).
  • the starting materials can also be formed in situ, so that they are not isolated from the reaction mixture, but instead are immediately reacted further to give the compounds of the formula I.
  • the compounds of the formula I can preferably be obtained by reacting compounds of the formula II with compounds of the formula III.
  • the compounds of the formula II are reacted with the compounds of the formula III in the presence or absence of an inert solvent at temperatures between about -20 and about 150 °, preferably between 20 and 100 °.
  • Suitable inert solvents are, for example, hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons such as trichlorethylene, 1, 2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; Alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; Glycol ethers such as ethylene glycol mono- methyl or monoethyl ether (methyl glycol or ethyl glycol), ethylene glycol dimethyl ether (diglyme); Ketones such as aceto ⁇ or butanone; Amides such as acetamide, dimethylacetamide or dimethylformamide (DM
  • Nitromethane or nitrobenzene Esters such as ethyl acetate or mixtures of the solvents mentioned.
  • Compounds of the formula I can furthermore be obtained by reacting compounds of the formula IV with compounds of the formula V.
  • the starting compounds of the formulas IV and V are generally known. If they are not known, they can be produced by methods known per se.
  • the radical -CO-L is a preactivated carboxylic acid, preferably a carboxylic acid halide.
  • Formula V is carried out under the same conditions, with regard to the reaction time, temperature and solvent, as described for the reaction of the compounds of the formula II with compounds of the formula III.
  • a base of the formula I can be converted into the associated acid addition salt using an acid, for example by reacting equivalent amounts of the base and the acid in an inert solvent such as ethanol and subsequent evaporation.
  • acids that provide physiologically acceptable salts are suitable for this implementation.
  • inorganic acids can be used, for example sulfuric acid, nitric acid, hydrohalic acids such as hydrochloric acid or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulfamic acid, furthermore organic acids, in particular aliphatic, alicyclic, araliphatic, aromatic or heterocyclic mono- or poly-based carbon, sulfonic or Sulfuric acids, e.g.
  • sensic acid acetic acid, propionic acid, pivaiic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methane or ethanesulfonic acid, 2-ethanesulfonic acid, ethanedisulfonic acid, ethanedisulfonic acid, ethanediol sulfonic acid, ethanedisulfonic acid, 2-ethanesulfonic acid, ethanediol sulfonic acid, ethanediol sulfonic acid, 2-ethanesulfonic acid, ethanediol sulfonic acid, 2-ethanesulfonic acid, ethanediol sulfonic acid
  • the free bases of formula I can be liberated from their salts with bases (e.g. sodium or potassium hydroxide or carbonate).
  • Suitable carriers are organic or inorganic substances which are suitable for enteral (e.g. oral), parenteral or topical application and do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate,
  • Gelatin carbohydrates such as lactose or starch, magnesium stearate, talc, petroleum jelly. Tablets, pills, dragees, capsules, powders, granules, syrups, juices or drops are used for oral use, suppositories for rectal use, solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants for topical use for parenteral use Ointments, creams or powder.
  • the new compounds can also be lyophilized and the resulting lyophilisates e.g. can be used for the production of injectables.
  • the specified preparations can be sterilized and / or contain auxiliaries such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, coloring, flavoring and / or one or more further active ingredients, e.g. one or more vitamins.
  • auxiliaries such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, coloring, flavoring and / or one or more further active ingredients, e.g. one or more vitamins.
  • Salts can be used to combat diseases in which an increase cAMP (cyclo-adenosine monophosphate) levels can be used to inhibit or prevent inflammation and to relax muscles.
  • the compounds according to the invention can be used particularly in the treatment of osteoporosis, tumors, asthma, chronic bronchitis, atopic dermatitis, psoriasis and other skin diseases and autoimmune diseases.
  • the substances according to the invention are generally preferably administered in doses between about 1 and 500 mg, in particular between 5 and 100 mg, per dosage unit.
  • the daily dosage is preferably between about 0.02 and 10 mg / kg body weight.
  • the specific dose for each patient depends on a wide variety of factors, for example on the effectiveness of the particular compound used, on the age, body weight, general health, sex, on the diet, on the time and route of administration, on the rate of excretion and on the combination of drugs and severity of the respective disease to which the therapy applies. Oral application is preferred.
  • Compounds of formula I can contain one or more centers of asymmetry. In this case, they are usually in racemic form. Racemates obtained can be separated into their enantiomers mechanically or chemically by methods known per se. Diastereomers are preferably formed from the racemic mixture by reaction with an optically active release agent.
  • optically active compounds of the formula I by the methods described above by using starting materials which are already optically active.
  • Formula I encompasses all stereoisomers and their mixtures, e.g. the racemate.
  • customary work-up means: if necessary, water is added, if necessary, depending on the constitution of the End product to pH values between 2 and 10, extracted with ethyl acetate or dichloromethane, separated, dried, the organic phase over sodium sulfate, evaporated and purified by chromatography on silica gel and / or by crystallization.
  • a suspension of 4.70 g of 3- (3,4-dimethoxyphenyl) -1, 4,5,6-tetrahydropyridazine ("A") in 150 ml of THF is mixed with 2.24 g of potassium tert-butoxide and stirred for 30 minutes.
  • 7.3 g of 4-nicotinoylaminobenzoyl chloride are added and the mixture is stirred at room temperature for 10 hours. The solvent is removed and worked up as usual.
  • Example A Injection glasses
  • a solution of 100 g of an active ingredient of the formula I and 5 g of disodium hydrogenphosphate is adjusted to pH 6.5 in 3 l of double-distilled water with 2N hydrochloric acid, sterile filtered, filled into injection glasses, lyophilized under sterile conditions and sealed sterile. Each injection gias contains 5 mg of active ingredient.
  • each suppository contains 20 mg of active ingredient.
  • a solution of 1 g of an active ingredient is prepared of the formula I, 9.38 g of NaH 2 P0 4 • 2 H 2 0, 28.48 g Na 2 HP0 4 • 12 H 2 0 and 0.1 g of benzalkonium chloride in 940 ml of double distilled water. It is adjusted to pH 6.8, made up to 1 I and sterilized by irradiation. This solution can be used in the form of eye drops.
  • Example D ointment
  • 500 mg of an active ingredient of the formula I are mixed with 99.5 g of petroleum jelly under aseptic conditions.
  • a mixture of 1 kg of active ingredient of the formula I, 4 kg of lactose, 1, 2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed into tablets in a conventional manner such that each tablet contains 10 mg of active ingredient.
  • Example F coated tablets
  • Example E tablets are pressed, which are then coated in a conventional manner with a coating of sucrose, potato starch, talc, tragacanth and colorant.
  • Example G capsules
  • each capsule contains 20 mg of the active ingredient.
  • a solution of 1 kg of active ingredient of the formula I in 60 l of double-distilled water is sterile filtered, filled into ampoules, lyophilized under sterile conditions and sealed sterile. Each ampoule contains 10 mg of active ingredient.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Virology (AREA)
  • Emergency Medicine (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • AIDS & HIV (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Cette invention concerne l'utilisation de composés de formule (I) dans laquelle R<1>, R<2>, Q et B ont les significations données dans la revendication 1, et/ou leurs sels physiologiquement admissibles, pour la fabrication d'un produit pharmaceutique permettant de traiter l'ostéoporose, les tumeurs, l'athérosclérose, l'arthrite rhumatoïde, la sclérose en plaques, le diabète sucré, la colite ulcéreuse et le SIDA.
EP00916949A 1999-04-06 2000-03-15 Utilisation d'arylalcanoylpyridazines Withdrawn EP1143944A3 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19915364 1999-04-06
DE19915364A DE19915364A1 (de) 1999-04-06 1999-04-06 Verwendung von Arylalkanoylpyridazinen
PCT/EP2000/002280 WO2000059484A2 (fr) 1999-04-06 2000-03-15 Utilisation d'arylalcanoylpyridazines

Publications (2)

Publication Number Publication Date
EP1143944A2 true EP1143944A2 (fr) 2001-10-17
EP1143944A3 EP1143944A3 (fr) 2002-09-11

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EP00916949A Withdrawn EP1143944A3 (fr) 1999-04-06 2000-03-15 Utilisation d'arylalcanoylpyridazines

Country Status (18)

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EP (1) EP1143944A3 (fr)
JP (1) JP2002541095A (fr)
KR (1) KR20020000550A (fr)
CN (1) CN1355702A (fr)
AR (1) AR023261A1 (fr)
AU (1) AU3811600A (fr)
BR (1) BR0009549A (fr)
CA (1) CA2367051A1 (fr)
CZ (1) CZ20013598A3 (fr)
DE (1) DE19915364A1 (fr)
HU (1) HUP0200311A3 (fr)
ID (1) ID30381A (fr)
MX (1) MXPA01010034A (fr)
NO (1) NO20014845D0 (fr)
PL (1) PL350963A1 (fr)
RU (1) RU2001129703A (fr)
WO (1) WO2000059484A2 (fr)
ZA (1) ZA200109120B (fr)

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Publication number Priority date Publication date Assignee Title
US20050096322A1 (en) * 2002-03-01 2005-05-05 Susumu Igarashi Nitrogen-containing heterocyclic compound
DE10224888A1 (de) * 2002-06-05 2003-12-24 Merck Patent Gmbh Pyridazinderivate
DE10225574A1 (de) * 2002-06-10 2003-12-18 Merck Patent Gmbh Aryloxime
CA2529558A1 (fr) * 2003-07-01 2005-01-13 Astellas Pharma Inc. Agent d'induction de croissance dans la masse osseuse
AR067354A1 (es) 2007-06-29 2009-10-07 Sunesis Pharmaceuticals Inc Compuestos utiles como inhibidores de la raf quinasa

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Publication number Priority date Publication date Assignee Title
DE19632549A1 (de) * 1996-08-13 1998-02-19 Merck Patent Gmbh Arylalkanoylpyridazine
DE19826841A1 (de) * 1998-06-16 1999-12-23 Merck Patent Gmbh Arylalkanoylpyridazine
DE19850701A1 (de) * 1998-11-04 2000-05-11 Merck Patent Gmbh Benzoylpyridazine
DE19915365A1 (de) * 1999-04-06 2000-10-12 Merck Patent Gmbh Tetrahydropyridazin-Derivate

Non-Patent Citations (1)

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Title
See references of WO0059484A2 *

Also Published As

Publication number Publication date
DE19915364A1 (de) 2000-10-12
NO20014845L (no) 2001-10-05
JP2002541095A (ja) 2002-12-03
ZA200109120B (en) 2003-11-13
CA2367051A1 (fr) 2000-10-12
NO20014845D0 (no) 2001-10-05
WO2000059484A2 (fr) 2000-10-12
HUP0200311A2 (hu) 2002-11-28
AU3811600A (en) 2000-10-23
ID30381A (id) 2001-11-29
EP1143944A3 (fr) 2002-09-11
PL350963A1 (en) 2003-02-24
HUP0200311A3 (en) 2002-12-28
BR0009549A (pt) 2002-03-26
KR20020000550A (ko) 2002-01-05
AR023261A1 (es) 2002-09-04
MXPA01010034A (es) 2002-04-24
CN1355702A (zh) 2002-06-26
WO2000059484A3 (fr) 2001-08-23
RU2001129703A (ru) 2004-02-20
CZ20013598A3 (cs) 2002-01-16

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