DE602004009407T2 - Thienopyridazinon-derivate als modulatoren von autoimmunkrankheiten - Google Patents
Thienopyridazinon-derivate als modulatoren von autoimmunkrankheiten Download PDFInfo
- Publication number
- DE602004009407T2 DE602004009407T2 DE602004009407T DE602004009407T DE602004009407T2 DE 602004009407 T2 DE602004009407 T2 DE 602004009407T2 DE 602004009407 T DE602004009407 T DE 602004009407T DE 602004009407 T DE602004009407 T DE 602004009407T DE 602004009407 T2 DE602004009407 T2 DE 602004009407T2
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- formula
- carbonyl
- dimethyl
- hydroxy
- 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.)
- Expired - Lifetime
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- 208000023275 Autoimmune disease Diseases 0.000 title abstract description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 76
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 48
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000001301 oxygen Substances 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 10
- 125000005843 halogen group Chemical group 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
- 239000012453 solvate Substances 0.000 claims abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 160
- -1 cyano, hydroxymethyl Chemical group 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 27
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- VOIKXRQSXFJVMT-UHFFFAOYSA-N 5h-thieno[2,3-d]pyridazin-4-one Chemical compound O=C1NN=CC2=C1C=CS2 VOIKXRQSXFJVMT-UHFFFAOYSA-N 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
- 229910052717 sulfur Chemical group 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
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- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 3
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- 238000004519 manufacturing process Methods 0.000 claims description 3
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- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- XXTOWQJOBJZSEY-VWLOTQADSA-N 2-[(3,5-dimethyl-1-pyrimidin-2-ylpyrazol-4-yl)methyl]-3-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-5-methyl-7-propan-2-ylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NN(C=2N=CC=CN=2)C(C)=C1CC=1SC=2C(C(C)C)=NN(C)C(=O)C=2C=1C(=O)N1C[C@](C)(O)CO1 XXTOWQJOBJZSEY-VWLOTQADSA-N 0.000 claims description 2
- ZIHOSOLLBUYLKY-LBPRGKRZSA-N 2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-5-methyl-7-propan-2-ylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC=1SC=2C(C(C)C)=NN(C)C(=O)C=2C=1C(=O)N1C[C@H](O)CO1 ZIHOSOLLBUYLKY-LBPRGKRZSA-N 0.000 claims description 2
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 206010062016 Immunosuppression Diseases 0.000 claims description 2
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- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 230000001506 immunosuppresive effect Effects 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
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- 239000000243 solution Substances 0.000 description 51
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- 235000019439 ethyl acetate Nutrition 0.000 description 34
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 30
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
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- YNLMJEPXHLXGRQ-ZDUSSCGKSA-N methyl 2-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C(=O)N1OC[C@@](C)(O)C1 YNLMJEPXHLXGRQ-ZDUSSCGKSA-N 0.000 description 1
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- HAWUPFPGLDIOFA-UHFFFAOYSA-N n-methoxy-n,2-dimethylpropanamide Chemical compound CON(C)C(=O)C(C)C HAWUPFPGLDIOFA-UHFFFAOYSA-N 0.000 description 1
- IQYRPZAMBNATNQ-UHFFFAOYSA-N n-methoxy-n-methylcyclopropanecarboxamide Chemical compound CON(C)C(=O)C1CC1 IQYRPZAMBNATNQ-UHFFFAOYSA-N 0.000 description 1
- YKVJZSZZQKQJMO-UHFFFAOYSA-N n-methoxy-n-methylpropanamide Chemical compound CCC(=O)N(C)OC YKVJZSZZQKQJMO-UHFFFAOYSA-N 0.000 description 1
- 230000025020 negative regulation of T cell proliferation Effects 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
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- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
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- RUUOPSRRIKJHNH-UHFFFAOYSA-N pyridazine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=N1 RUUOPSRRIKJHNH-UHFFFAOYSA-N 0.000 description 1
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- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 1
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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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 1
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Classifications
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Landscapes
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Applications Claiming Priority (3)
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| SE0300120 | 2003-01-17 | ||
| SE0300120A SE0300120D0 (sv) | 2003-01-17 | 2003-01-17 | Novel compounds |
| PCT/SE2004/000051 WO2004065393A1 (en) | 2003-01-17 | 2004-01-15 | Novel compounds |
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| DE602004009407D1 DE602004009407D1 (de) | 2007-11-22 |
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| GB0118479D0 (en) | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
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| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| RU2332420C2 (ru) * | 2003-01-17 | 2008-08-27 | Астразенека Аб | Тиенопиримидиндионы и их применение в модулировании аутоиммунного заболевания |
| CA2550361C (en) | 2003-12-19 | 2014-04-29 | Prabha Ibrahim | Compounds and methods for development of ret modulators |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| AU2006272951A1 (en) | 2005-05-17 | 2007-02-01 | Plexxikon, Inc. | Pyrrol (2,3-b) pyridine derivatives protein kinase inhibitors |
| CN102206216B (zh) | 2005-06-22 | 2014-11-12 | 普莱希科公司 | 作为蛋白质激酶抑制剂的吡咯并[2,3-b]吡啶衍生物 |
| CN101528752A (zh) * | 2006-10-16 | 2009-09-09 | 辉瑞产品公司 | 治疗性吡唑基噻吩并吡啶 |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| AU2007336811A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2008079909A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| PE20081581A1 (es) | 2006-12-21 | 2008-11-12 | Plexxikon Inc | COMPUESTOS PIRROLO[2,3-b]PIRIDINAS COMO MODULADORES DE QUINASA |
| JP2010533729A (ja) | 2007-07-17 | 2010-10-28 | プレキシコン，インコーポレーテッド | キナーゼ調節のための化合物と方法、及びそのための適応 |
| KR101739994B1 (ko) | 2009-04-03 | 2017-05-25 | 에프. 호프만-라 로슈 아게 | 프로판-１-술폰산 ｛３-［５-（４-클로로-페닐）-１Ｈ-피롤로［２，３-ｂ］피리딘-３-카르보닐］-２，４-디플루오로-페닐｝-아미드 조성물 및 그의 용도 |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| NZ599866A (en) | 2009-11-06 | 2014-09-26 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| KR101911972B1 (ko) | 2011-02-07 | 2018-10-25 | 플렉시콘 인코퍼레이티드 | 키나제 조절을 위한 화합물 및 방법, 및 그에 대한 적응증 |
| TWI558702B (zh) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | 醫藥活性物質的固態形式 |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| US9200005B2 (en) | 2013-03-13 | 2015-12-01 | AbbVie Deutschland GmbH & Co. KG | Inhibitor compounds of phosphodiesterase type 10A |
| MY184561A (en) * | 2013-10-21 | 2021-04-03 | Genosco | Substituted pyrimidine compounds and their use as syk inhibitors |
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|---|---|---|---|---|
| DE3620860A1 (de) * | 1986-06-21 | 1987-12-23 | Basf Ag | Substituierte acrylsaeureester und fungizide, die diese verbindungen enthalten |
| US6469014B1 (en) * | 1997-05-28 | 2002-10-22 | Astrazeneca Ab | Thieno[2,3-d] pyrimidinediones, their preparation and use in therapy |
| SE9702001D0 (sv) * | 1997-05-28 | 1997-05-28 | Astra Pharma Prod | Novel compounds |
| IL136499A0 (en) * | 1997-12-05 | 2001-06-14 | Astrazeneca Uk Ltd Astrazeneca | Pyrrolo-, thieno-, furano- and pyrazolo-[3,4,d] pypyrrolo-, thieno-, furano- and pyrazolo-[3,4,d] pyridazinone compounds, process for their preparatioridaziones compounds, process for their preparation, pharmaceutical compositions containing them, a n, pharmaceutical compositions containing them, a process for prepating the pharmaceutical compositiprocess for preparing the pharmaceutical compositions, and use thereof ons, and use thereof |
| US6232320B1 (en) * | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| ATE253580T1 (de) | 1998-08-28 | 2003-11-15 | Astrazeneca Ab | Neue thieno(2,3-d)pyrimidindione, verfahren für ihre herstellung und ihre verwendung in der therapie |
| GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| SE0300119D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| RU2332420C2 (ru) * | 2003-01-17 | 2008-08-27 | Астразенека Аб | Тиенопиримидиндионы и их применение в модулировании аутоиммунного заболевания |
-
2003
- 2003-01-17 SE SE0300120A patent/SE0300120D0/xx unknown
-
2004
- 2004-01-15 ES ES04702471T patent/ES2293208T3/es not_active Expired - Lifetime
- 2004-01-15 US US10/542,194 patent/US7064126B2/en not_active Expired - Fee Related
- 2004-01-15 WO PCT/SE2004/000051 patent/WO2004065393A1/en not_active Ceased
- 2004-01-15 PL PL378223A patent/PL378223A1/pl unknown
- 2004-01-15 UA UAA200506375A patent/UA80175C2/uk unknown
- 2004-01-15 AU AU2004205617A patent/AU2004205617B2/en not_active Ceased
- 2004-01-15 CN CNB2004800071016A patent/CN100358900C/zh not_active Expired - Fee Related
- 2004-01-15 EP EP04702471A patent/EP1587809B1/en not_active Expired - Lifetime
- 2004-01-15 DE DE602004009407T patent/DE602004009407T2/de not_active Expired - Lifetime
- 2004-01-15 KR KR1020057013124A patent/KR20050092759A/ko not_active Abandoned
- 2004-01-15 AT AT04702471T patent/ATE375352T1/de not_active IP Right Cessation
- 2004-01-15 CA CA002512736A patent/CA2512736A1/en not_active Abandoned
- 2004-01-15 RU RU2005121493/04A patent/RU2331646C2/ru not_active IP Right Cessation
- 2004-01-15 NZ NZ541216A patent/NZ541216A/en not_active IP Right Cessation
- 2004-01-15 BR BR0406780-0A patent/BRPI0406780A/pt not_active IP Right Cessation
- 2004-01-15 JP JP2006500749A patent/JP4589298B2/ja not_active Expired - Fee Related
- 2004-01-15 MX MXPA05007494A patent/MXPA05007494A/es active IP Right Grant
-
2005
- 2005-06-23 IL IL169363A patent/IL169363A/en not_active IP Right Cessation
- 2005-06-29 ZA ZA200505273A patent/ZA200505273B/xx unknown
- 2005-08-15 NO NO20053827A patent/NO20053827L/no not_active Application Discontinuation
- 2005-08-15 IS IS7982A patent/IS2503B/is unknown
-
2006
- 2006-06-06 US US11/447,343 patent/US20060223809A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| IS2503B (is) | 2009-04-15 |
| JP4589298B2 (ja) | 2010-12-01 |
| ZA200505273B (en) | 2006-04-26 |
| ES2293208T3 (es) | 2008-03-16 |
| EP1587809B1 (en) | 2007-10-10 |
| CN1761670A (zh) | 2006-04-19 |
| SE0300120D0 (sv) | 2003-01-17 |
| IS7982A (is) | 2005-08-15 |
| HK1081958A1 (en) | 2006-05-26 |
| RU2005121493A (ru) | 2006-02-20 |
| EP1587809A1 (en) | 2005-10-26 |
| US7064126B2 (en) | 2006-06-20 |
| CA2512736A1 (en) | 2004-08-05 |
| NO20053827D0 (no) | 2005-08-15 |
| AU2004205617A1 (en) | 2004-08-05 |
| PL378223A1 (pl) | 2006-03-20 |
| ATE375352T1 (de) | 2007-10-15 |
| KR20050092759A (ko) | 2005-09-22 |
| RU2331646C2 (ru) | 2008-08-20 |
| MXPA05007494A (es) | 2005-09-21 |
| IL169363A0 (en) | 2007-07-04 |
| CN100358900C (zh) | 2008-01-02 |
| NZ541216A (en) | 2008-05-30 |
| JP2006515373A (ja) | 2006-05-25 |
| IL169363A (en) | 2011-02-28 |
| US20060052380A1 (en) | 2006-03-09 |
| UA80175C2 (en) | 2007-08-27 |
| NO20053827L (no) | 2005-10-17 |
| DE602004009407D1 (de) | 2007-11-22 |
| US20060223809A1 (en) | 2006-10-05 |
| WO2004065393A1 (en) | 2004-08-05 |
| AU2004205617B2 (en) | 2007-03-08 |
| BRPI0406780A (pt) | 2006-01-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8381 | Inventor (new situation) |
Inventor name: COOPER, MARTIN E., HORSHOLM, DK Inventor name: INGALL, ANTHONY H., LOUGHBOROUGH, LEICS. LE11 , GB Inventor name: GUILE, SIMON D., LOUGHBOROUGH, LEICS. LE11 5RH, GB Inventor name: RASUL, RUKHSANA T., LOUGHBOROUGH, LEICS. LE11 , GB |
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| 8364 | No opposition during term of opposition |