JP2005538140A - Ｐｄｅ４インヒビターとしてのピペリジン−ピリダゾン及びフタラゾン - Google Patents
Ｐｄｅ４インヒビターとしてのピペリジン−ピリダゾン及びフタラゾン Download PDFInfo
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- JP2005538140A JP2005538140A JP2004530096A JP2004530096A JP2005538140A JP 2005538140 A JP2005538140 A JP 2005538140A JP 2004530096 A JP2004530096 A JP 2004530096A JP 2004530096 A JP2004530096 A JP 2004530096A JP 2005538140 A JP2005538140 A JP 2005538140A
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- alkoxy
- hydrogen
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- aryl
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- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 title claims abstract description 10
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title claims abstract description 10
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 title description 3
- KHSHUCGBOGKFDA-UHFFFAOYSA-N piperidine;1h-pyridazin-6-one Chemical compound C1CCNCC1.O=C1C=CC=NN1 KHSHUCGBOGKFDA-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- -1 pteridinyl Benzoxazolyl Chemical group 0.000 claims description 204
- 229910052739 hydrogen Inorganic materials 0.000 claims description 123
- 239000001257 hydrogen Substances 0.000 claims description 123
- 125000003118 aryl group Chemical group 0.000 claims description 98
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 56
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 56
- 125000002971 oxazolyl group Chemical group 0.000 claims description 56
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 56
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 56
- 150000002431 hydrogen Chemical group 0.000 claims description 54
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 52
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims description 48
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 48
- 125000001544 thienyl group Chemical group 0.000 claims description 48
- 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
- 229910052731 fluorine Inorganic materials 0.000 claims description 39
- 239000011737 fluorine Substances 0.000 claims description 39
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 36
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 36
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 30
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=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
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 30
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 30
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 28
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 25
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 20
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 14
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- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 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
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 10
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 7
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 7
- 150000002430 hydrocarbons Chemical group 0.000 claims description 7
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 5
- 125000003003 spiro group Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 3
- HALXACJSIHOJCA-LEWJYISDSA-N (4as,8ar)-2-[1-[3-(2-aminoethylsulfonyl)propanoyl]piperidin-4-yl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)CCS(=O)(=O)CCN)CC1 HALXACJSIHOJCA-LEWJYISDSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 230000001668 ameliorated effect Effects 0.000 claims description 2
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- IBVWOCYYNDUFJP-LEWJYISDSA-N (4as,8ar)-2-[1-[3-(2-aminoethylsulfanyl)propanoyl]piperidin-4-yl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C([C@H]1CC=CC[C@H]1C1=O)=NN1C1CCN(C(=O)CCSCCN)CC1 IBVWOCYYNDUFJP-LEWJYISDSA-N 0.000 claims 1
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims 1
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- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
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- 239000012876 carrier material Substances 0.000 claims 1
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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- 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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- 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
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- 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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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02017977 | 2002-08-10 | ||
| PCT/EP2003/008724 WO2004017974A1 (en) | 2002-08-10 | 2003-08-06 | Piperidine-pyridazones and phthalazones as pde4 inhibitors |
Publications (1)
| Publication Number | Publication Date |
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| JP2005538140A true JP2005538140A (ja) | 2005-12-15 |
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| JP2004530096A Pending JP2005538140A (ja) | 2002-08-10 | 2003-08-06 | Ｐｄｅ４インヒビターとしてのピペリジン−ピリダゾン及びフタラゾン |
| JP2004530086A Expired - Fee Related JP4555684B2 (ja) | 2002-08-10 | 2003-08-06 | Ｐｄｅ４阻害剤としての、ピロリジンジオンにより置換されたピペリジン−フタラゾン |
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| JP2004530086A Expired - Fee Related JP4555684B2 (ja) | 2002-08-10 | 2003-08-06 | Ｐｄｅ４阻害剤としての、ピロリジンジオンにより置換されたピペリジン−フタラゾン |
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| JP (2) | JP2005538140A (enExample) |
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| AU (2) | AU2003258576B2 (enExample) |
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| RS (1) | RS51445B (enExample) |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010526852A (ja) * | 2007-05-16 | 2010-08-05 | 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 | Ｐｄｅ４インヒビターとしてのピラゾロン誘導体 |
| JP2012508720A (ja) * | 2008-11-14 | 2012-04-12 | 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 | 新規のピラゾロン誘導体及び該誘導体をｐｄｅ４インヒビターとして用いる使用 |
| JP2014517021A (ja) * | 2011-06-17 | 2014-07-17 | タケダ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規のフタラジノン−ピロロピリミジンカルボキサミド誘導体 |
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| EA200300836A1 (ru) | 2001-02-15 | 2004-02-26 | Алтана Фарма Аг | Производные фталазинон-пиперидина в качестве ингибиторов pde4 |
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| 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 |
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| PE20080361A1 (es) | 2006-04-21 | 2008-06-03 | Novartis Ag | Compuestos derivados de purina como activadores del receptor de adenosina a2a |
| AU2007302263A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as P13K lipid kinase inhibitors |
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| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
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| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| ES2558457T3 (es) | 2011-09-16 | 2016-02-04 | Novartis Ag | Compuestos heterocíclicos para el tratamiento de fibrosis quística |
| EP2755652B1 (en) | 2011-09-16 | 2021-06-02 | Novartis AG | N-substituted heterocyclyl carboxamides |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU8722991A (en) * | 1990-10-16 | 1992-05-20 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Arylpyridazinones |
| ATE183745T1 (de) | 1991-10-09 | 1999-09-15 | Syntex Inc | Pyrido pyridazinon und pyridazinthionverbindungen mit pde iv inhibierender wirkung |
| US5716954A (en) * | 1991-10-09 | 1998-02-10 | Syntex U.S.A. Inc. | Benzopyridazinone and pyridopyridazinone compounds |
| CA2400368A1 (en) | 1992-12-02 | 1994-06-09 | Allen J. Duplantier | Catechol diethers as selective pde iv inhibitors |
| 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 |
| HUP0001541A3 (en) * | 1997-01-15 | 2001-11-28 | Altana Pharma Ag | Phthalazinone derivatives and pharmaceutical compositions containing them |
| US6380196B1 (en) * | 1997-12-15 | 2002-04-30 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Dihydrobenzofurans |
| WO1999031071A1 (en) | 1997-12-15 | 1999-06-24 | Byk Gulden Lomberg Chemische Fabrik Gmbh | New phthalazinones |
| US6255303B1 (en) * | 1998-03-14 | 2001-07-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinone PDE III/IV inhibitors |
| AU7654200A (en) | 1999-09-14 | 2001-04-17 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinone derivatives as pd3/4 inhibitors |
| EP1244654A1 (en) | 1999-10-25 | 2002-10-02 | ALTANA Pharma AG | Tetrahydrothiopy ranphthalazinone derivatives as pde4 inhibitors |
| CA2388121A1 (en) | 1999-10-25 | 2001-05-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinone derivatives as pde 4 inhibitors |
| NZ522882A (en) * | 2000-06-05 | 2004-07-30 | Altana Pharma Bv | Pyridazinone compounds effective as beta-2-adrenoreceptor agonists as well as PDE4-inhibitors |
| EA200300836A1 (ru) * | 2001-02-15 | 2004-02-26 | Алтана Фарма Аг | Производные фталазинон-пиперидина в качестве ингибиторов pde4 |
| DE10112864A1 (de) * | 2001-03-16 | 2002-09-19 | Alstom Switzerland Ltd | Verfahren zum Zünden einer thermischen Turbomaschine |
| PL363312A1 (en) * | 2001-04-25 | 2004-11-15 | Altana Pharma Ag | Novel phthalazinones |
| SK14352003A3 (sk) * | 2001-04-25 | 2004-04-06 | Altana Pharma Ag | Piperazino-deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
-
2003
- 2003-08-06 KR KR1020057001920A patent/KR101131684B1/ko not_active Expired - Fee Related
- 2003-08-06 WO PCT/EP2003/008724 patent/WO2004017974A1/en not_active Ceased
- 2003-08-06 JP JP2004530096A patent/JP2005538140A/ja active Pending
- 2003-08-06 EP EP03792267A patent/EP1556049A1/en not_active Withdrawn
- 2003-08-06 BR BR0313330-3A patent/BR0313330A/pt not_active Application Discontinuation
- 2003-08-06 CA CA002494634A patent/CA2494634A1/en not_active Abandoned
- 2003-08-06 MX MXPA05001354A patent/MXPA05001354A/es active IP Right Grant
- 2003-08-06 AT AT03792257T patent/ATE360627T1/de active
- 2003-08-06 JP JP2004530086A patent/JP4555684B2/ja not_active Expired - Fee Related
- 2003-08-06 PL PL03372926A patent/PL372926A1/xx not_active Application Discontinuation
- 2003-08-06 PL PL373645A patent/PL214701B1/pl unknown
- 2003-08-06 EP EP03792257A patent/EP1537100B1/en not_active Expired - Lifetime
- 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 HR HR20050198A patent/HRP20050198A2/hr not_active Application Discontinuation
- 2003-08-06 WO PCT/EP2003/008675 patent/WO2004018457A1/en not_active Ceased
- 2003-08-06 US US10/523,111 patent/US20060094710A1/en not_active Abandoned
- 2003-08-06 US US10/523,412 patent/US7220746B2/en not_active Expired - Fee Related
- 2003-08-06 CA CA2494613A patent/CA2494613C/en not_active Expired - Fee Related
- 2003-08-06 ES ES03792257T patent/ES2286491T3/es not_active Expired - Lifetime
- 2003-08-06 CN CNA038185202A patent/CN1671695A/zh active Pending
- 2003-08-06 RS YUP-2005/0112A patent/RS51445B/sr unknown
- 2003-08-06 DE DE60313472T patent/DE60313472T2/de not_active Expired - Lifetime
-
2005
- 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 IS IS7721A patent/IS7721A/is unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010526852A (ja) * | 2007-05-16 | 2010-08-05 | 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 | Ｐｄｅ４インヒビターとしてのピラゾロン誘導体 |
| JP2014159452A (ja) * | 2007-05-16 | 2014-09-04 | Takeda Gmbh | Ｐｄｅ４インヒビターとしてのピラゾロン誘導体 |
| JP2012508720A (ja) * | 2008-11-14 | 2012-04-12 | 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 | 新規のピラゾロン誘導体及び該誘導体をｐｄｅ４インヒビターとして用いる使用 |
| JP2014517021A (ja) * | 2011-06-17 | 2014-07-17 | タケダ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規のフタラジノン−ピロロピリミジンカルボキサミド誘導体 |
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