HRP20050198A2 - Piperidin-piridazoni i ftalazoni kao inhibitori pde4 - Google Patents
Piperidin-piridazoni i ftalazoni kao inhibitori pde4Info
- Publication number
- HRP20050198A2 HRP20050198A2 HR20050198A HRP20050198A HRP20050198A2 HR P20050198 A2 HRP20050198 A2 HR P20050198A2 HR 20050198 A HR20050198 A HR 20050198A HR P20050198 A HRP20050198 A HR P20050198A HR P20050198 A2 HRP20050198 A2 HR P20050198A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkoxy
- hydrogen
- alkyl
- integer
- formula
- Prior art date
Links
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title claims abstract description 11
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title claims abstract description 11
- KHSHUCGBOGKFDA-UHFFFAOYSA-N piperidine;1h-pyridazin-6-one Chemical class C1CCNCC1.O=C1C=CC=NN1 KHSHUCGBOGKFDA-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 157
- -1 cinolinyl Chemical group 0.000 claims description 229
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 123
- 229910052739 hydrogen Inorganic materials 0.000 claims description 123
- 239000001257 hydrogen Substances 0.000 claims description 123
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 62
- 150000002431 hydrogen Chemical group 0.000 claims description 57
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 56
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 56
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 56
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 56
- 125000002971 oxazolyl group Chemical group 0.000 claims description 56
- 125000001544 thienyl group Chemical group 0.000 claims description 56
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 55
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 55
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 51
- 125000001153 fluoro group Chemical group F* 0.000 claims description 50
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 50
- 229910052731 fluorine Inorganic materials 0.000 claims description 49
- 239000011737 fluorine Substances 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000002541 furyl group Chemical group 0.000 claims description 42
- 125000002883 imidazolyl group Chemical group 0.000 claims description 42
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 42
- 125000001041 indolyl group Chemical group 0.000 claims description 42
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 42
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 42
- 125000005493 quinolyl group Chemical group 0.000 claims description 42
- 125000000335 thiazolyl group Chemical group 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 30
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 30
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 30
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 30
- 125000001624 naphthyl group Chemical group 0.000 claims description 30
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 28
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 28
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 18
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- 238000000034 method Methods 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 14
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 12
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- 239000001301 oxygen Substances 0.000 claims description 12
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 11
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
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- SYGWYBOJXOGMRU-UHFFFAOYSA-N chembl233051 Chemical group C1=CC=C2C3=CC(C(N(CCN(C)C)C4=O)=O)=C5C4=CC=CC5=C3SC2=C1 SYGWYBOJXOGMRU-UHFFFAOYSA-N 0.000 claims 5
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
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- A61P31/04—Antibacterial agents
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- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
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- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- 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
- A61P37/08—Antiallergic agents
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- 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
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- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- 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
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
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- Rheumatology (AREA)
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- Virology (AREA)
- Communicable Diseases (AREA)
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- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
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- Ophthalmology & Optometry (AREA)
- Toxicology (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
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- Endocrinology (AREA)
- Reproductive Health (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02017977 | 2002-08-10 | ||
| PCT/EP2003/008724 WO2004017974A1 (fr) | 2002-08-10 | 2003-08-06 | Piperidine-pyridazones et phthalazones en tant qu'inhibiteurs de pde4 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20050198A2 true HRP20050198A2 (hr) | 2006-04-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20050198A HRP20050198A2 (hr) | 2002-08-10 | 2005-03-01 | Piperidin-piridazoni i ftalazoni kao inhibitori pde4 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20060094710A1 (fr) |
| EP (2) | EP1537100B1 (fr) |
| JP (2) | JP4555684B2 (fr) |
| KR (1) | KR101131684B1 (fr) |
| CN (1) | CN1671695A (fr) |
| AT (1) | ATE360627T1 (fr) |
| AU (2) | AU2003258576B2 (fr) |
| BR (1) | BR0313330A (fr) |
| CA (2) | CA2494634A1 (fr) |
| DE (1) | DE60313472T2 (fr) |
| ES (1) | ES2286491T3 (fr) |
| HR (1) | HRP20050198A2 (fr) |
| IL (1) | IL166271A (fr) |
| IS (2) | IS2416B (fr) |
| MX (1) | MXPA05001354A (fr) |
| PL (2) | PL214701B1 (fr) |
| RS (1) | RS51445B (fr) |
| WO (2) | WO2004018457A1 (fr) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA03007310A (es) | 2001-02-15 | 2003-12-04 | Altana Pharma Ag | Derivados de ftalazinona piperidino como inhibidores pde4. |
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| KR101179012B1 (ko) | 2003-03-10 | 2012-09-03 | 니코메드 게엠베하 | 로플루미라스트 신규한 제조 방법 |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| US20080227790A1 (en) * | 2004-02-04 | 2008-09-18 | Altana Pharma Ag | Pyridazinone Derivatives and their Use as Pde4 Inhibitors |
| US7494990B2 (en) | 2004-02-04 | 2009-02-24 | Nycomed Gmbh | 2-(piperidin-4-yl)-4,5-dihydro-2H-pyridazin-3-one derivatives as PDE4 inhibitors |
| JP2007536350A (ja) * | 2004-05-10 | 2007-12-13 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 肺気腫の予防又は治療のためのロフルミラストの使用 |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| EP1861074B1 (fr) | 2005-03-16 | 2013-04-24 | Takeda GmbH | Forme de dosage cachant le goût comprenant du roflumilaste |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| RU2421464C2 (ru) | 2005-10-21 | 2011-06-20 | Новартис Аг | Человеческие антитела к il-13 и их терапевтическое применение |
| GB0526244D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| NZ571429A (en) | 2006-04-21 | 2011-09-30 | Novartis Ag | Purine derivatives for use as adenosine A2A receptor agonists |
| RU2009115954A (ru) | 2006-09-29 | 2010-11-10 | Новартис АГ (CH) | Пиразолопиримидины в качестве ингибиторов липидной киназы р13к |
| WO2008052734A1 (fr) | 2006-10-30 | 2008-05-08 | Novartis Ag | Composés hétérocycliques en tant qu'agents anti-inflammatoires |
| JP2010515729A (ja) | 2007-01-10 | 2010-05-13 | アイアールエム・リミテッド・ライアビリティ・カンパニー | チャネル活性化プロテアーゼ阻害剤としての化合物および組成物 |
| WO2008127898A1 (fr) * | 2007-04-11 | 2008-10-23 | Martinez Rodolfo A | Synthons précurseurs contenant un seul carbone |
| PL2155721T3 (pl) | 2007-05-07 | 2011-07-29 | Novartis Ag | Związki organiczne |
| RS52074B (en) * | 2007-05-16 | 2012-06-30 | Nycomed Gmbh | PIRAZOLONE DERIVATED AS PDE4 INHIBITORS |
| WO2009074575A2 (fr) | 2007-12-10 | 2009-06-18 | Novartis Ag | Composés organiques |
| JP5584138B2 (ja) | 2008-01-11 | 2014-09-03 | ノバルティス アーゲー | キナーゼ阻害剤としてのピリミジン類 |
| JP2011522860A (ja) | 2008-06-10 | 2011-08-04 | ノバルティス アーゲー | 上皮性ナトリウムチャネルブロッカーとしてのピラジン誘導体 |
| AR074318A1 (es) | 2008-11-14 | 2011-01-05 | Nycomed Gmbh | Derivados heterociclicos de pirazolona, composiciones farmaceuticas que los contienen y uso de los mismos para el tratamiento de enfermedades de las vias respiratorias. |
| SI2391366T1 (sl) | 2009-01-29 | 2013-01-31 | Novartis Ag | Substituirani benzimidazoli za zdravljenje astrocitomov |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| AU2010283806A1 (en) | 2009-08-12 | 2012-03-01 | Novartis Ag | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
| GEP201706639B (en) | 2009-08-17 | 2017-03-27 | Intellikine Llc | Heterocyclic compounds and uses thereof |
| BR112012008061A2 (pt) | 2009-08-20 | 2016-03-01 | Novartis Ag | compostos de oxima heterocíclica |
| MX2012004792A (es) | 2009-10-22 | 2013-02-01 | Vertex Pharma | Composiciones para el tratamiento de fibrosis quistica y otras enfermedades cronicas. |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| WO2012034095A1 (fr) | 2010-09-09 | 2012-03-15 | Irm Llc | Composés et compositions comme inhibiteurs de trk |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン， エルエルシー | 複素環化合物およびその使用 |
| AU2012220572A1 (en) | 2011-02-25 | 2013-08-29 | Irm Llc | Compounds and compositions as trk inhibitors |
| AR086915A1 (es) * | 2011-06-17 | 2014-01-29 | Nycomed Gmbh | Derivados de ftalazinona-pirrolopirimidinacarboxamida y composiciones farmaceuticas que los contiene |
| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| US9062045B2 (en) | 2011-09-15 | 2015-06-23 | Novartis Ag | Triazolopyridine compounds |
| WO2013038373A1 (fr) | 2011-09-16 | 2013-03-21 | Novartis Ag | Dérivés pyrimidinamides |
| JP6165733B2 (ja) | 2011-09-16 | 2017-07-19 | ノバルティス アーゲー | Ｎ−置換ヘテロシクリルカルボキサミド類 |
| WO2013038378A1 (fr) | 2011-09-16 | 2013-03-21 | Novartis Ag | Dérivés pyridinamides |
| WO2013038381A1 (fr) | 2011-09-16 | 2013-03-21 | Novartis Ag | Dérivés d'amide pyridine/pyrazine |
| US9034879B2 (en) | 2011-09-16 | 2015-05-19 | Novartis Ag | Heterocyclic compounds for the treatment of CF |
| JP6130391B2 (ja) | 2011-11-23 | 2017-05-17 | インテリカイン， エルエルシー | Ｍｔｏｒ阻害剤を使用する強化された治療レジメン |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| CN110507654A (zh) | 2012-04-03 | 2019-11-29 | 诺华有限公司 | 有酪氨酸激酶抑制剂的组合产品和其应用 |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| EP2968340A4 (fr) | 2013-03-15 | 2016-08-10 | Intellikine Llc | Combinaison d'inhibiteurs de kinase et ses utilisations |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| BR112016023967A2 (pt) | 2014-04-24 | 2017-08-15 | Novartis Ag | derivados de pirazina como inibidores de fosfatidilinositol 3-cinase |
| EP3134397A1 (fr) | 2014-04-24 | 2017-03-01 | Novartis AG | Dérivés aminés de pyrazine utilisables en tant qu'inhibiteurs de la phosphatidylinositol 3-kinase |
| EP3134396B1 (fr) | 2014-04-24 | 2019-09-18 | Novartis AG | Dérivés aminés de pyridine utilisables en tant qu'inhibiteurs de la phosphatidylinositol 3-kinase |
| WO2016011658A1 (fr) | 2014-07-25 | 2016-01-28 | Novartis Ag | Polythérapie |
| CA2954862A1 (fr) | 2014-07-31 | 2016-02-04 | Novartis Ag | Polytherapie |
| BR112021024668A2 (pt) | 2019-06-10 | 2022-05-31 | Novartis Ag | Derivado de piridina e pirazina para o tratamento de fc, dpoc e bronquiectasia |
| CN110330465B (zh) * | 2019-06-28 | 2021-05-11 | 深圳市三启药物开发有限公司 | 腙酰胺类衍生物及其在制备防治脱发药物中的应用 |
| WO2021038426A1 (fr) | 2019-08-28 | 2021-03-04 | Novartis Ag | Dérivés de 1,3-phényl hétéroaryle substitués et leur utilisation dans le traitement d'une maladie |
Family Cites Families (18)
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| JPH06501941A (ja) * | 1990-10-16 | 1994-03-03 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | アリールピリダジノン |
| US5716954A (en) * | 1991-10-09 | 1998-02-10 | Syntex U.S.A. Inc. | Benzopyridazinone and pyridopyridazinone compounds |
| WO1993007146A1 (fr) | 1991-10-09 | 1993-04-15 | Syntex (U.S.A.) Inc. | Composes benzo et pyrido pyridazinones et pyridazinthiones a activite inhibant la phosphodiesterase iv |
| CA2150812C (fr) | 1992-12-02 | 2002-12-24 | Allen J. Duplantier | Diethers de catechol utilises comme inhibiteurs selectifs de la phosphodiesterase de type iv |
| DE19533975A1 (de) | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| US5658940A (en) * | 1995-10-06 | 1997-08-19 | Celgene Corporation | Succinimide and maleimide cytokine inhibitors |
| ES2193508T3 (es) * | 1997-01-15 | 2003-11-01 | Altana Pharma Ag | Ftalizinonas. |
| WO1999031071A1 (fr) | 1997-12-15 | 1999-06-24 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Nouveaux phtalazinones |
| ATE258930T1 (de) | 1997-12-15 | 2004-02-15 | Altana Pharma Ag | Dihydrobenzifurane |
| ATE270278T1 (de) | 1998-03-14 | 2004-07-15 | Altana Pharma Ag | Phthalazinone pde iii/iv hemmer |
| WO2001019818A1 (fr) | 1999-09-14 | 2001-03-22 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Derives de phthalazinone utilises comme inhibiteurs de pd3/4 |
| PL354979A1 (en) | 1999-10-25 | 2004-03-22 | Altana Pharma Ag | Tetrahydrothiopy ranphthalazinone derivatives as pde4 inhibitors |
| CA2388121A1 (fr) * | 1999-10-25 | 2001-05-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Derives de phthalazinone, utilises comme inhibiteurs de pde4 |
| AU6233201A (en) * | 2000-06-05 | 2001-12-17 | Byk Gulden Lomberg Chem Fab | Compounds effective as beta-2-adrenoreceptor agonists as well as pde4-inhibitors |
| MXPA03007310A (es) * | 2001-02-15 | 2003-12-04 | Altana Pharma Ag | Derivados de ftalazinona piperidino como inhibidores pde4. |
| DE10112864A1 (de) * | 2001-03-16 | 2002-09-19 | Alstom Switzerland Ltd | Verfahren zum Zünden einer thermischen Turbomaschine |
| MXPA03009583A (es) * | 2001-04-25 | 2004-02-12 | Altana Pharma Ag | Ftalazinonas novedosas. |
| KR20030089723A (ko) | 2001-04-25 | 2003-11-22 | 알타나 파마 아게 | 피페라지노-유도체 및 이것의 ｐｄｅ4 억제제로서의 용도 |
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2003
- 2003-08-06 JP JP2004530086A patent/JP4555684B2/ja not_active Expired - Fee Related
- 2003-08-06 DE DE60313472T patent/DE60313472T2/de not_active Expired - Lifetime
- 2003-08-06 CN CNA038185202A patent/CN1671695A/zh active Pending
- 2003-08-06 CA CA002494634A patent/CA2494634A1/fr not_active Abandoned
- 2003-08-06 US US10/523,111 patent/US20060094710A1/en not_active Abandoned
- 2003-08-06 WO PCT/EP2003/008675 patent/WO2004018457A1/fr active IP Right Grant
- 2003-08-06 US US10/523,412 patent/US7220746B2/en not_active Expired - Fee Related
- 2003-08-06 AU AU2003258576A patent/AU2003258576B2/en not_active Ceased
- 2003-08-06 AU AU2003260376A patent/AU2003260376A1/en not_active Abandoned
- 2003-08-06 EP EP03792257A patent/EP1537100B1/fr not_active Expired - Lifetime
- 2003-08-06 WO PCT/EP2003/008724 patent/WO2004017974A1/fr not_active Application Discontinuation
- 2003-08-06 CA CA2494613A patent/CA2494613C/fr not_active Expired - Fee Related
- 2003-08-06 BR BR0313330-3A patent/BR0313330A/pt not_active Application Discontinuation
- 2003-08-06 AT AT03792257T patent/ATE360627T1/de active
- 2003-08-06 RS YUP-2005/0112A patent/RS51445B/en unknown
- 2003-08-06 PL PL373645A patent/PL214701B1/pl unknown
- 2003-08-06 ES ES03792257T patent/ES2286491T3/es not_active Expired - Lifetime
- 2003-08-06 EP EP03792267A patent/EP1556049A1/fr not_active Withdrawn
- 2003-08-06 PL PL03372926A patent/PL372926A1/xx not_active Application Discontinuation
- 2003-08-06 KR KR1020057001920A patent/KR101131684B1/ko not_active IP Right Cessation
- 2003-08-06 JP JP2004530096A patent/JP2005538140A/ja active Pending
- 2003-08-06 MX MXPA05001354A patent/MXPA05001354A/es active IP Right Grant
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- 2005-01-13 IL IL166271A patent/IL166271A/en not_active IP Right Cessation
- 2005-02-28 IS IS7718A patent/IS2416B/is unknown
- 2005-03-01 HR HR20050198A patent/HRP20050198A2/hr not_active Application Discontinuation
- 2005-03-01 IS IS7721A patent/IS7721A/is unknown
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