EP1435958A1 - Verwendung von phosphodiesterase iv - inhibitoren - Google Patents

Verwendung von phosphodiesterase iv - inhibitoren

Info

Publication number
EP1435958A1
EP1435958A1 EP02777150A EP02777150A EP1435958A1 EP 1435958 A1 EP1435958 A1 EP 1435958A1 EP 02777150 A EP02777150 A EP 02777150A EP 02777150 A EP02777150 A EP 02777150A EP 1435958 A1 EP1435958 A1 EP 1435958A1
Authority
EP
European Patent Office
Prior art keywords
ethyl
dihydro
benzyl
methoxyphenyl
dimethoxyphenyl
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Withdrawn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
EP02777150A
Other languages
German (de)
English (en)
French (fr)
Inventor
Hans-Michael Eggenweiler
Michael Wolf
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=7702358&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP1435958(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of EP1435958A1 publication Critical patent/EP1435958A1/de
Withdrawn legal-status Critical Current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
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • 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
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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
    • 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

  • the invention relates to the use of compounds of the formula I, disclosed in EP 0 738 715 A2,
  • R 1 and R 2 each independently of one another H or A
  • R 3 and R 4 each independently of one another -OH, -OR 10 , -SR 10 ,
  • R 5 is an unsubstituted or mono- or disubstituted by R 6 and / or R 7 substituted phenyl radical
  • Q is absent or alkylene with 1-6 C atoms
  • R 6 and R 7 each independently of one another -NH 2 , -NR 8 R 9 , -NHR 10 ,
  • R 8 and R 9 each independently of one another H, acyl with 1-8 C atoms, which is replaced by 1-5 F and / or Cl atoms can be substituted, -COOA, -SO-A, -S0 2 A, -CONH 2l -CONHA, -CONA 2 , -CO-COOH, -CO-COOA, -CO-CONH 2 , - CO-CONHA or -CO-CONA 2 , A alkyl with 1 to 6 carbon atoms, which by 1-5 F and / or
  • Cl atoms can be substituted, R 10 and R 11 each independently of one another A, cycloalkyl with 3-7 C atoms, methylene cycloalkyl with 4-8 C atoms or alkenyl with 2-8 C atoms and Hal F, Cl, Br or I mean
  • R 1 and R 2 are each independently H or A
  • R 3 and R 4 each independently of one another -OH, -OR 10 , -SR 10 ,
  • R 5 is an unsubstituted or mono- or disubstituted phenyl radical R 6 and / or R 7 , Q is absent or alkylene with 1 -6 C atoms,
  • R 6 and R 7 each independently of one another -NH 2) -NR 8 R 9 , -NHR 10 , -NR 10 R 11 , -N0 2 , shark, -CN, -OA, -COOH or -COOA, R 8 and R 9 each independently of one another H, acyl with 1 -8 C-
  • Atoms which can be substituted by 1-5 F and / or Cl atoms, -COOA, -SO-A, -S0 2 A, -CONH 2) -CONHA, -CONA 2 , -CO-COOH, -CO -COOA, -CO-CONH 2l -CO-CONHA or -CO-CONA 2 ,
  • a alkyl with 1 to 6 carbon atoms which is represented by 1 -5 F and / or
  • Cl atoms can be substituted, R 10 and R 1 each independently of one another A, cycloalkyl with 3-7 C atoms, methylene cycloalkyl with 4-8 C atoms or alkenyl with 2-8 C atoms and
  • B is an aromatic heterocycle with 1 to 4 N, O and / or S atoms, bonded via N or C, which may be unsubstituted or substituted once, twice or three times by shark, A and / or OA, and can also be fused to a benzene or pyridine ring,
  • Q is absent or alkylene with 1 -6 C atoms
  • R 1 and R 2 are each independently H or A
  • R 3 and R 4 each independently of one another -OH, OR 5 , -SR 5 , -SO-R 5 , -S0 2 -R 5 , shark, methylenedioxy, -N0 2l -NH 2 , -NHR 5 or -NR 5 R 6 ,
  • R 5 and R 6 each independently of one another A, cycloalkyl with 3-7 C atoms, methylene cycloalkyl with 4-8 C atoms or alkenyl with 2-8 C atoms,
  • a alkyl having 1 to 10 carbon atoms, which can be substituted by 1 to 5 F and / or Cl atoms and Hal F, Cl, Broder I mean
  • R 1 and R 2 each independently of one another H or A, R 3 H, OA or O-C m H 2m + 1-n X n ,
  • A is alkyl with 1-6 C atoms, m is 1, 2, 3, 4, 5 or 6 and n is 1,2,3,4,5,6,7,8,9, 10, 11, 12 or 13 .
  • R 1 and R 2 are each independently H or A, R 3 and R 4 each independently of one another OH, OA, SA, SOA, S0 2 A, shark, methylenedioxy, cycloalkyloxy with 3-7 C atoms or 0-C m H 2m + 1-k F k ,
  • R 6 and R 7 each independently of one another H or A, Q alkylene with 1 -6 C atoms,
  • R 1 and R 2 are each independently H or A
  • R 3 and R 4 each independently of one another -OH, OA, -SA,
  • Atoms that are substituted by 1 to 5 F and / or Cl atoms can be tuiert, cycloalkyl with 3-7 C-atoms or methylene cycloalkyl with 4-8 C-atoms,
  • Q is absent or alkylene with 1 -4 C atoms
  • Y is absent or alkylene with 1 -10 C atoms
  • NHA NHA
  • NAA an unsubstituted or simply substituted by A or OH saturated 3-8-membered heterocycle with at least one N atom, in which further CH 2 groups have been replaced by NH, NA, S or O.
  • the object of the invention was to find new uses of the compounds of the formulas I, in particular those which can lead to the production of medicaments.
  • 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 compounds also show an inhibitory effect on the formation of TNF (tumor necrosis factor) and are therefore suitable for the 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. described in EP 779 291.
  • the anti-inflammatory effect of the substances according to the invention and their effectiveness for the treatment of, for example, 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 invention furthermore relates to the use of the compounds of the formulas I and their physiologically acceptable salts and / or solvates for the production of a medicament for inhibiting the growth of neoplastic cells.
  • Neoplastic cells are understood to mean cancer cells.
  • the invention relates in particular to the use of the compounds of the formulas I and their physiologically acceptable salts and / or solvates for the production of a medicament for the treatment and / or prophylaxis of cancer.
  • the invention furthermore relates to the use of the compounds of the formulas I and their physiologically acceptable salts and / or solvates for the production of a medicament for the treatment of neoplastic damage.
  • the invention furthermore relates to the use of the compounds of the formulas I and their physiologically acceptable salts and / or solvates for the production of a medicament for the treatment of precancerogenic damage.
  • Precancerogenic damage means, for example, benign growths in the intestine that can lead to colon cancer.
  • Precancerogenic damage includes in particular those in US
  • Irregularities in apoptosis play a role in the formation of precancerogenic damage. Regulation of apoptosis is also known to play an important role in diseases associated with abnormal cell growth, such as e.g. benign prostatic hyperplasia, neurodegenerative diseases, e.g. Parkinson's, autoimmune diseases including multiple sclerosis and rheumatoid arthritis or infectious diseases such as AIDS.
  • diseases associated with abnormal cell growth such as e.g. benign prostatic hyperplasia, neurodegenerative diseases, e.g. Parkinson's, autoimmune diseases including multiple sclerosis and rheumatoid arthritis or infectious diseases such as AIDS.
  • the compounds of the formula I modulate apoptosis and are used in the treatment or prophylaxis of cancer.
  • the invention thus relates to the use of the compounds of the formulas I and their physiologically acceptable salts and / or solvates for the production of a medicament for regulating apoptosis in human cells.
  • the compounds of the formulas I can be used as active pharmaceutical ingredients in human and veterinary medicine. They can also be used as intermediates for the production of further active pharmaceutical ingredients.
  • the compounds of the formulas 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-
  • parenteral or topical application and do not react with the new compounds, e.g. 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 in particular for oral use, suppositories for rectal use, solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants for which topical application 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, eg one or more vitamins.
  • the compounds of the formulas I and their physiologically acceptable salts can be used in combating diseases in which an increase in the cAMP (cyclo-adenosine monophosphate) level leads to inhibition or prevention of inflammation and muscle relaxation.
  • cAMP cyclo-adenosine monophosphate
  • Particular use can be made of the invention
  • the substances according to the invention are generally preferably used in doses between about 1 and 500 mg, in particular between see 5 and 100 mg administered 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 the 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.
  • the invention relates in particular to the use of a) compounds, disclosed in EP 0 738 715 A2, selected from the
EP02777150A 2001-10-12 2002-09-19 Verwendung von phosphodiesterase iv - inhibitoren Withdrawn EP1435958A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10150517A DE10150517A1 (de) 2001-10-12 2001-10-12 Verwendung von Phosphodiesterase IV-Inhibitoren
DE10150517 2001-10-12
PCT/EP2002/010507 WO2003032993A1 (de) 2001-10-12 2002-09-19 Verwendung von phosphodiesterase iv - inhibitoren

Publications (1)

Publication Number Publication Date
EP1435958A1 true EP1435958A1 (de) 2004-07-14

Family

ID=7702358

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02777150A Withdrawn EP1435958A1 (de) 2001-10-12 2002-09-19 Verwendung von phosphodiesterase iv - inhibitoren

Country Status (15)

Country Link
US (1) US20040235845A1 (no)
EP (1) EP1435958A1 (no)
JP (1) JP2005505604A (no)
KR (1) KR20050028900A (no)
CN (1) CN1564687A (no)
AR (1) AR037741A1 (no)
AU (1) AU2002338734B2 (no)
CA (1) CA2460135C (no)
CZ (1) CZ2004457A3 (no)
DE (1) DE10150517A1 (no)
HU (1) HUP0401641A3 (no)
MX (1) MXPA04002639A (no)
NO (1) NO20041938L (no)
SK (1) SK1652004A3 (no)
WO (1) WO2003032993A1 (no)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007504201A (ja) * 2003-09-05 2007-03-01 アルタナ　ファルマ　アクチエンゲゼルシャフト 真性糖尿病の治療のためのｐｄｅ４阻害剤の使用
EP1716123A1 (en) * 2004-02-04 2006-11-02 Altana Pharma AG Pyridazinone derivatives and their use as pde4 inhibitors
AU2005210042B2 (en) 2004-02-04 2011-04-21 Takeda Gmbh 2-(piperidin-4-yl) -4, 5-dihydro-2H-pyridazin-3-one derivatives as PDE4 inhibitors
US8017633B2 (en) 2005-03-08 2011-09-13 Nycomed Gmbh Roflumilast for the treatment of diabetes mellitus
DE102005055355A1 (de) * 2005-11-21 2007-10-31 Merck Patent Gmbh 3,6-Dihydro-2-oxo-6H-[1,3,4]thiadiazinderivate
DE102005055354A1 (de) * 2005-11-21 2007-10-31 Merck Patent Gmbh Substituierte 5-Phenyl-3,6-dihydro-2-oxo-6H-[1,3,4]thiadiazine
MX2009002282A (es) * 2006-09-07 2009-03-20 Nycomed Gmbh Tratamiento de combinacion para diabetes mellitius.
AP2015008663A0 (en) 2013-02-19 2015-08-31 Pfizer Azabenzimidazole compounds as inhibitors of PDE4 isozymes for the treatment of cns and other disorders
JP6713982B2 (ja) 2014-07-24 2020-06-24 ファイザー・インク ピラゾロピリミジン化合物
CU20170007A7 (es) 2014-08-06 2017-06-05 Pfizer Compuestos de imidazopiridazina
RU2626677C1 (ru) * 2016-03-09 2017-07-31 Федеральное государственное автономное образовательное учреждение высшего образования "Уральский федеральный университет имени первого Президента России Б.Н. Ельцина" Применение фармацевтической композиции 2-морфолино-5-фенил-6н-1,3,4-тиадиазина с аскорбиновой кислотой в качестве средства коррекции аллоксанового сахарного диабета

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4134893A1 (de) * 1991-10-23 1993-04-29 Merck Patent Gmbh Thiadiazinone
DE4310699A1 (de) * 1993-04-01 1994-10-06 Merck Patent Gmbh Thiadiazinone
US5786354A (en) * 1994-06-21 1998-07-28 Celltech Therapeutics, Limited Tri-substituted phenyl derivatives and processes for their preparation
DE19502699A1 (de) * 1995-01-28 1996-08-01 Merck Patent Gmbh Arylalkyl-thiadiazinone
DE19514568A1 (de) * 1995-04-20 1996-10-24 Merck Patent Gmbh Arylalkyl-pyridazinone
DE19533975A1 (de) * 1995-09-14 1997-03-20 Merck Patent Gmbh Arylalkyl-diazinone
GB9525262D0 (en) * 1995-12-11 1996-02-07 Bayer Ag Heterocyclylcarbonyl substituted benzofuranyl-ureas
DE19604388A1 (de) * 1996-02-07 1997-08-14 Merck Patent Gmbh Arylalkyl-diazinone
US5948911A (en) * 1998-11-20 1999-09-07 Cell Pathways, Inc. Method for inhibiting neoplastic cells and related conditions by exposure to thienopyrimidine derivatives

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03032993A1 *

Also Published As

Publication number Publication date
NO20041938L (no) 2004-05-11
CZ2004457A3 (cs) 2005-04-13
HUP0401641A2 (hu) 2004-11-29
SK1652004A3 (sk) 2005-05-05
CN1564687A (zh) 2005-01-12
CA2460135C (en) 2010-08-24
CA2460135A1 (en) 2003-04-24
MXPA04002639A (es) 2004-06-07
HUP0401641A3 (en) 2007-02-28
JP2005505604A (ja) 2005-02-24
AR037741A1 (es) 2004-12-01
KR20050028900A (ko) 2005-03-23
US20040235845A1 (en) 2004-11-25
DE10150517A1 (de) 2003-04-17
WO2003032993A1 (de) 2003-04-24
AU2002338734B2 (en) 2007-11-08

Similar Documents

Publication Publication Date Title
EP0763534B1 (de) Arylalkyl-diazinone als Phosphodiesterase IV-Hemmer
DE60005504T2 (de) Chinolinderivate als mek enzym-inhibitoren
DE60006099T2 (de) Chinolinderivate als mek enzym-inhibitoren
EP0922036B1 (de) Arylalkanoylpyridazine
EP0360077B1 (de) Verwendung von Serotonin-Antagonisten bei der Behandlung von Apoplexia cerebri
EP1435958A1 (de) Verwendung von phosphodiesterase iv - inhibitoren
DE60215139T2 (de) Malonyl coa-decarboxylase inhibitoren als stoffwechselmodulatoren
DE19826841A1 (de) Arylalkanoylpyridazine
EP1124809B1 (de) Benzoylpyridazine
EP0738715A2 (de) Arylalkyl-pyridazinone
WO2005060955A1 (de) Pharmazeutische zusammensetzung aus einem beta-3-adrenozeptor-agonisten und einem in den prostaglandinstoffwechsel eingreifendem wirkstoff
DE10155076A1 (de) Verwendung von Endothelin-Rezeptor-Antagonisten zur Behandlung von Tumorerkrankungen
EP0723962B1 (de) Arylalkyl-thiadiazinone
DE19915365A1 (de) Tetrahydropyridazin-Derivate
EP0539806B1 (de) Thiadiazinone und sie enthaltende Arzneimittel, insbesondere mit Positiv-Inotroper und vasodilatierender Wirksamkeit
DD287491A5 (de) Verfahren zur herstellung von substituierten styrolderivaten
DE3031703C2 (no)
JPS6351328A (ja) 脳細胞保護作用を有する医薬組成物
EP1143944A3 (de) Verwendung von arylalkanoylpyridazinen
DD275241A5 (de) Verfahren zur herstellung von neuen 1-aryloxy-3-amimo-2-propanolen
DE3444135C2 (no)
DE10156229A1 (de) Triazinderivate
DE10156230A1 (de) Tyrosinhydrazide
DE19944332A1 (de) Antikonvulsiv und anxiolytisch wirkende 4-Amino-1-aryl-1,5-dihydro-pyrrol-2-one und Verfahren zu deren Herstellung
DE1817346A1 (de) Herzwirksame Praeparate auf der Basis von Methylanthinen

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20040316

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

17Q First examination report despatched

Effective date: 20040702

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Effective date: 20050718