CA2470813A1 - 1,4-dihydro-1,4-diphenylpyridine derivatives - Google Patents
1,4-dihydro-1,4-diphenylpyridine derivatives Download PDFInfo
- Publication number
- CA2470813A1 CA2470813A1 CA002470813A CA2470813A CA2470813A1 CA 2470813 A1 CA2470813 A1 CA 2470813A1 CA 002470813 A CA002470813 A CA 002470813A CA 2470813 A CA2470813 A CA 2470813A CA 2470813 A1 CA2470813 A1 CA 2470813A1
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- CA
- Canada
- Prior art keywords
- compounds
- general formula
- amino
- methyl
- mmol
- 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.)
- Abandoned
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- RLTOXDSOOSYULO-UHFFFAOYSA-N 1,4-diphenyl-4h-pyridine Chemical class C1=CN(C=2C=CC=CC=2)C=CC1C1=CC=CC=C1 RLTOXDSOOSYULO-UHFFFAOYSA-N 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 21
- 230000008569 process Effects 0.000 claims abstract description 19
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 80
- -1 trifluoromethoxy, amino Chemical group 0.000 claims description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 8
- 108010028275 Leukocyte Elastase Proteins 0.000 claims description 7
- 102000016799 Leukocyte elastase Human genes 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical group C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 230000008578 acute process Effects 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000002849 elastaseinhibitory effect Effects 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 33
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 239000003480 eluent Substances 0.000 description 23
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 22
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- 238000010992 reflux Methods 0.000 description 18
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
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- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 102000016387 Pancreatic elastase Human genes 0.000 description 8
- 108010067372 Pancreatic elastase Proteins 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000000758 substrate Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
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- 230000000694 effects Effects 0.000 description 5
- 229920002549 elastin Polymers 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 206010014561 Emphysema Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
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- 239000012131 assay buffer Substances 0.000 description 4
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- 201000010251 cutis laxa Diseases 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 102100033174 Neutrophil elastase Human genes 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
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- VGVXOXSRINSIFO-UHFFFAOYSA-N 3-(diethylaminomethyl)aniline Chemical compound CCN(CC)CC1=CC=CC(N)=C1 VGVXOXSRINSIFO-UHFFFAOYSA-N 0.000 description 2
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 2
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- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0130553A GB2383326A (en) | 2001-12-20 | 2001-12-20 | Antiinflammatory dihydropyridines |
| GB0130553.1 | 2001-12-20 | ||
| GB0216664.3 | 2002-07-17 | ||
| GB0216664A GB2390849A (en) | 2002-07-17 | 2002-07-17 | 3-Acyl-1,4-dihydro-1,4-di(phenyl/azinyl/diazinyl)pyridine derivatives for use as human neutrophil elastase inhibitors |
| PCT/EP2002/013931 WO2003053930A1 (en) | 2001-12-20 | 2002-12-09 | 1,4-dihydro-1,4-diphenylpyridine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2470813A1 true CA2470813A1 (en) | 2003-07-03 |
Family
ID=26246892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002470813A Abandoned CA2470813A1 (en) | 2001-12-20 | 2002-12-09 | 1,4-dihydro-1,4-diphenylpyridine derivatives |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7199136B2 (enExample) |
| EP (1) | EP1458682B1 (enExample) |
| JP (1) | JP4486817B2 (enExample) |
| AU (1) | AU2002361992A1 (enExample) |
| CA (1) | CA2470813A1 (enExample) |
| DE (1) | DE60214428T2 (enExample) |
| ES (1) | ES2271365T3 (enExample) |
| WO (1) | WO2003053930A1 (enExample) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0219896D0 (en) | 2002-08-27 | 2002-10-02 | Bayer Ag | Dihydropyridine derivatives |
| AU2003255492A1 (en) * | 2002-09-10 | 2004-04-30 | Bayer Healthcare Ag | Heterocyclic derivatives |
| SE0302487D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
| CA2556463C (en) * | 2004-02-19 | 2012-08-14 | Bayer Healthcare Ag | Dihydropyridinone derivatives |
| JP4825194B2 (ja) * | 2004-02-26 | 2011-11-30 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | １，４−ジアリール−ジヒドロピリミジン−２−オン化合物およびヒト好中球エラスターゼ阻害剤としてのそれらの使用 |
| EP1730121B1 (en) | 2004-02-26 | 2013-08-07 | Bayer Intellectual Property GmbH | 1,4-diaryl-dihydropyrimidin-2-ones and their use as human neutrophil elastase inhibitors |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| US7994211B2 (en) | 2005-08-08 | 2011-08-09 | Argenta Discovery Limited | Bicyclo[2.2.1]hept-7-ylamine derivatives and their uses |
| DE102007019690A1 (de) | 2007-04-26 | 2008-10-30 | Bayer Healthcare Ag | Verwendung von cyclisch substituierten Furopyrimidin-Derivaten zur Behandlung der pulmonalen arteriellen Hypertonie |
| DE102007019691A1 (de) | 2007-04-26 | 2008-10-30 | Bayer Healthcare Ag | Verwendung von acyclisch substituierten Furopyrimidin-Derivaten zur Behandlung der pulmonalen arteriellen Hypertonie |
| DE102007027800A1 (de) | 2007-06-16 | 2008-12-18 | Bayer Healthcare Ag | Substituierte bicyclische Heteroaryl-Verbindungen und ihre Verwendung |
| DE102007027799A1 (de) | 2007-06-16 | 2008-12-18 | Bayer Healthcare Ag | Substituierte Furopyrimidine und ihre Verwendung |
| DE102007051762A1 (de) | 2007-10-30 | 2009-05-07 | Bayer Healthcare Ag | Substituierte Pyrrolotriazine und ihre Verwendung |
| DE102007054786A1 (de) | 2007-11-16 | 2009-05-20 | Bayer Healthcare Ag | Trisubstituierte Furopyrimidine und ihre Verwendung |
| PT2229358E (pt) | 2007-12-14 | 2011-06-29 | Pulmagen Therapeutics Asthma Ltd | Indoles e sua utilização terapêutica |
| DE102008007400A1 (de) | 2008-02-04 | 2009-08-06 | Bayer Healthcare Ag | Substituierte Furane und ihre Verwendung |
| DE102009004197A1 (de) * | 2009-01-09 | 2010-07-15 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclisch anellierte Diaryldihydropyrimidin-Derivate und ihre Verwendung |
| AU2010215261A1 (en) | 2009-02-17 | 2011-09-08 | Chiesi Farmaceutici S.P.A. | Triazolopyridine derivatives as p38 MAP kinase inhibitors |
| GB0902648D0 (en) | 2009-02-17 | 2009-04-01 | Argenta Discovery Ltd | Pharmaceutical compounds and compositions |
| GB0918922D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
| GB0918924D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Azaindole derivatives |
| GB0918923D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminothiazole derivatives |
| GB201009731D0 (en) | 2010-06-10 | 2010-07-21 | Pulmagen Therapeutics Inflamma | Kinase inhibitors |
| CN103974953B (zh) | 2011-12-09 | 2016-06-29 | 奇斯药制品公司 | 激酶抑制剂 |
| CN103987708B (zh) | 2011-12-09 | 2016-06-22 | 奇斯药制品公司 | 4-羟基-1,2,3,4-四氢萘-1-基脲的衍生物及其在呼吸道疾病治疗中的用途 |
| CN105968110B (zh) | 2011-12-09 | 2018-04-27 | 奇斯药制品公司 | 激酶抑制剂 |
| US20140221335A1 (en) | 2013-02-06 | 2014-08-07 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9115093B2 (en) | 2013-03-04 | 2015-08-25 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| WO2014195402A1 (en) | 2013-06-06 | 2014-12-11 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| US9440930B2 (en) | 2014-07-31 | 2016-09-13 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9657015B2 (en) | 2014-07-31 | 2017-05-23 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9290457B2 (en) * | 2014-07-31 | 2016-03-22 | Boehringer Ingelheim International Gmbh | Substituted dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9475779B2 (en) | 2014-07-31 | 2016-10-25 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9458113B2 (en) | 2014-07-31 | 2016-10-04 | Boehringer Ingelheim International Gmbh | Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity |
| US9958484B2 (en) * | 2015-07-08 | 2018-05-01 | Qualcomm Incorporated | Apparatus and method for measuring load current by applying compensated gain to voltage derived from drain-to-source voltage of power gating device |
| TW201720828A (zh) | 2015-11-23 | 2017-06-16 | 赫孚孟拉羅股份公司 | 治療性化合物及組合物以及其使用方法 |
| EP3394058B1 (en) | 2015-12-23 | 2020-10-14 | Chiesi Farmaceutici S.p.A. | N-[3-(3-{4-[[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl} -ureido)-phenyl]-methanesulfonamide derivatives and their use as p38 mapk inhibitors |
| EP3394060A1 (en) | 2015-12-23 | 2018-10-31 | Chiesi Farmaceutici S.p.A. | 1-(3-tert-butyl-2h-pyrazol-5-yl or 5-tert-butyl-isoxaol-3-yl)-3-(4-([1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalenyl) urea derivatives and their use as p38 mapk inhibitors |
| EP3394059B1 (en) | 2015-12-23 | 2020-11-25 | Chiesi Farmaceutici S.p.A. | 1-(3-tert-butyl-phenyl)-3-(4-([1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro- naphthalen-1-yl)-urea derivatives and their use as p38 mapk inhibitors |
| WO2017191098A1 (en) | 2016-05-05 | 2017-11-09 | F. Hoffmann-La Roche Ag | Pyrazole derivatives, compositions and therapeutic use thereof |
| CN109890817B (zh) | 2016-09-06 | 2022-06-17 | 豪夫迈·罗氏有限公司 | 8-(氮杂环丁烷-1-基)-[1,2,4]三唑并[1,5-a]吡啶基化合物、其组合物和应用方法 |
| CN110114343B (zh) | 2016-12-29 | 2022-09-06 | 豪夫迈·罗氏有限公司 | 吡唑并嘧啶化合物及其使用方法 |
| WO2018166993A2 (en) | 2017-03-14 | 2018-09-20 | F. Hoffmann-La Roche Ag | Pyrazolochlorophenyl compounds, compositions and methods of use thereof |
| CN110678467B (zh) | 2017-05-22 | 2023-06-13 | 豪夫迈·罗氏有限公司 | 治疗化合物和组合物及其使用方法 |
| BR112019024322A2 (pt) | 2017-05-22 | 2020-06-16 | F. Hoffmann-La Roche Ag | Compostos e composições terapêuticos e métodos de uso dos mesmos |
| US10364245B2 (en) | 2017-06-07 | 2019-07-30 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| CN111587250A (zh) | 2018-01-15 | 2020-08-25 | 豪夫迈·罗氏有限公司 | 作为jak抑制剂的吡唑并嘧啶化合物 |
| JP2020015705A (ja) * | 2018-07-27 | 2020-01-30 | 住友化学株式会社 | アニリン化合物の製造方法 |
| MA56518A (fr) | 2019-06-18 | 2022-04-27 | Hoffmann La Roche | Inhibiteurs de sulfone pyrazolopyrimidine de jak kinases et leurs utilisations |
| TW202115069A (zh) | 2019-06-18 | 2021-04-16 | 瑞士商赫孚孟拉羅股份公司 | Ｊａｋ激酶之經四唑取代之吡唑并嘧啶抑制劑及其用途 |
| JP7716993B2 (ja) | 2019-06-18 | 2025-08-01 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | Ｊａｋキナーゼのピラゾロピリミジンアリールエーテル阻害剤及びその使用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2753946A1 (de) * | 1977-12-03 | 1979-06-13 | Bayer Ag | 1-n-aryl-1,4-dihydropyridine und ihre verwendung als arzneimittel |
| DE3222367A1 (de) | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Verwendung von 1,4-dihydropyridinen in antiarteriosklerotika und deren herstellung |
| DE4011695A1 (de) * | 1990-04-11 | 1991-10-17 | Bayer Ag | Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsaeureestern als arzneimittel, neue verbindungen und verfahren zu ihrer herstellung |
| DE4328884A1 (de) | 1993-08-27 | 1995-03-02 | Bayer Ag | Verwendung von N-alkylierten 1,4-Dihydropyridincarbonsäureestern als Arzneimittel |
| JP3337829B2 (ja) * | 1994-07-29 | 2002-10-28 | 日研化学株式会社 | １，４−ジヒドロピリジン化合物 |
-
2002
- 2002-12-09 AU AU2002361992A patent/AU2002361992A1/en not_active Abandoned
- 2002-12-09 WO PCT/EP2002/013931 patent/WO2003053930A1/en not_active Ceased
- 2002-12-09 DE DE60214428T patent/DE60214428T2/de not_active Expired - Lifetime
- 2002-12-09 ES ES02796589T patent/ES2271365T3/es not_active Expired - Lifetime
- 2002-12-09 EP EP02796589A patent/EP1458682B1/en not_active Expired - Lifetime
- 2002-12-09 US US10/498,967 patent/US7199136B2/en not_active Expired - Fee Related
- 2002-12-09 CA CA002470813A patent/CA2470813A1/en not_active Abandoned
- 2002-12-09 JP JP2003554646A patent/JP4486817B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60214428T2 (de) | 2007-09-20 |
| US7199136B2 (en) | 2007-04-03 |
| ES2271365T3 (es) | 2007-04-16 |
| JP2005517666A (ja) | 2005-06-16 |
| AU2002361992A1 (en) | 2003-07-09 |
| EP1458682A1 (en) | 2004-09-22 |
| US20050165014A1 (en) | 2005-07-28 |
| DE60214428D1 (de) | 2006-10-12 |
| JP4486817B2 (ja) | 2010-06-23 |
| WO2003053930A1 (en) | 2003-07-03 |
| EP1458682B1 (en) | 2006-08-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |