CN102171211A - 用作jak3抑制剂的哌啶衍生物 - Google Patents
用作jak3抑制剂的哌啶衍生物 Download PDFInfo
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- CN102171211A CN102171211A CN2009801396041A CN200980139604A CN102171211A CN 102171211 A CN102171211 A CN 102171211A CN 2009801396041 A CN2009801396041 A CN 2009801396041A CN 200980139604 A CN200980139604 A CN 200980139604A CN 102171211 A CN102171211 A CN 102171211A
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- Prior art keywords
- compound
- aryl
- heteroaryl
- formula
- alkyl group
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 34
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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Applications Claiming Priority (5)
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| US8570508P | 2008-08-01 | 2008-08-01 | |
| US61/085705 | 2008-08-01 | ||
| US9856208P | 2008-09-19 | 2008-09-19 | |
| US61/098562 | 2008-09-19 | ||
| PCT/US2009/052449 WO2010014930A2 (en) | 2008-08-01 | 2009-07-31 | Therapeutic agents |
Publications (1)
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|---|---|
| CN102171211A true CN102171211A (zh) | 2011-08-31 |
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Family Applications (1)
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| CN2009801396041A Pending CN102171211A (zh) | 2008-08-01 | 2009-07-31 | 用作jak3抑制剂的哌啶衍生物 |
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| US (1) | US20110165183A1 (https=) |
| EP (1) | EP2324020A2 (https=) |
| JP (1) | JP2011529918A (https=) |
| KR (1) | KR20110050654A (https=) |
| CN (1) | CN102171211A (https=) |
| AU (1) | AU2009276420A1 (https=) |
| BR (1) | BRPI0916931A2 (https=) |
| CA (1) | CA2732628A1 (https=) |
| IL (1) | IL210990A0 (https=) |
| MX (1) | MX2011001259A (https=) |
| NZ (1) | NZ590922A (https=) |
| RU (1) | RU2011105768A (https=) |
| WO (1) | WO2010014930A2 (https=) |
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| CN104059016A (zh) * | 2014-06-20 | 2014-09-24 | 湖南天地恒一制药有限公司 | 制备托法替布的中间体及所述中间体的制备方法 |
| CN105622616A (zh) * | 2016-02-25 | 2016-06-01 | 上海雅本化学有限公司 | 一种4-氯吡咯并嘧啶的制备方法 |
| CN105732637A (zh) * | 2014-12-30 | 2016-07-06 | 广东东阳光药业有限公司 | 杂芳化合物及其在药物中的应用 |
| CN107108630A (zh) * | 2014-08-29 | 2017-08-29 | 阳智化学（株） | 作为janus激酶抑制剂的被取代的n‑(吡咯烷‑3‑基)‑7h‑吡咯并[2,3‑d]嘧啶‑4‑胺 |
| CN109970745A (zh) * | 2018-04-16 | 2019-07-05 | 深圳市塔吉瑞生物医药有限公司 | 取代的吡咯并三嗪类化合物及其药物组合物及其用途 |
| RU2719477C2 (ru) * | 2015-06-22 | 2020-04-17 | Оно Фармасьютикал Ко., Лтд. | Соединение, ингибирующее brk |
| CN116768908A (zh) * | 2022-03-10 | 2023-09-19 | 石家庄迪斯凯威医药科技有限公司 | 一种含n多环化合物及其制备方法与用途 |
| CN117164519A (zh) * | 2023-08-18 | 2023-12-05 | 杭州小蓓医药科技有限公司 | 一种l-肌肽的合成方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2012107101A (ru) | 2009-07-31 | 2013-09-10 | Байокрист Фармасьютикалз, Инк. | Производные пирроло[1,2-в] пиридазина как ингибиторы янус-киназы |
| AU2011258005A1 (en) * | 2010-05-28 | 2013-01-17 | Biocryst Pharmaceuticals, Inc. | Heterocyclic compounds as Janus kinase inhibitors |
| CA2836417A1 (en) | 2011-05-17 | 2012-11-22 | Principia Biopharma Inc. | Azaindole derivatives as tyrosine kinase inhibitors |
| WO2013135671A1 (en) | 2012-03-13 | 2013-09-19 | Basf Se | Fungicidal pyrimidine compounds |
| ME03455B (me) | 2012-09-10 | 2020-01-20 | Principia Biopharma Inc | Jedinjenja pirazolopirimidina kao inhibitori kinaze |
| US9550785B2 (en) * | 2012-11-20 | 2017-01-24 | Glaxosmithkline Llc | Pyrrolopyrimidines as therapeutic agents for the treatment of diseases |
| US9481679B2 (en) * | 2012-12-17 | 2016-11-01 | Sun Pharmaceutical Industries Limited | Process for the preparation of tofacitinib and intermediates thereof |
| WO2014102826A1 (en) * | 2012-12-28 | 2014-07-03 | Glenmark Pharmaceuticals Limited; | The present invention relates to process for the preparation of tofacitinib and intermediates thereof. |
| WO2015036058A1 (en) | 2013-09-16 | 2015-03-19 | Basf Se | Fungicidal pyrimidine compounds |
| WO2015036059A1 (en) | 2013-09-16 | 2015-03-19 | Basf Se | Fungicidal pyrimidine compounds |
| BR112016006319A2 (pt) * | 2013-09-27 | 2017-08-01 | Nimbus Iris Inc | inibidores de irak e usos dos mesmos |
| SI3539965T1 (sl) * | 2013-12-09 | 2021-07-30 | Unichem Laboratories Limited | Izboljšan postopek za pripravo (3R,4R)-(1-benzil-4-metilpiperidin-3-il)-metilamina |
| PT3107544T (pt) | 2014-02-21 | 2021-01-05 | Principia Biopharma Inc | Sais e forma sólida de um inibidor de btk |
| CN104860950A (zh) * | 2014-02-24 | 2015-08-26 | 重庆医药工业研究院有限责任公司 | 一种制备4-氯吡咯[2,3-d]并嘧啶的方法 |
| US10485797B2 (en) | 2014-12-18 | 2019-11-26 | Principia Biopharma Inc. | Treatment of pemphigus |
| EP3078665A1 (en) * | 2015-04-10 | 2016-10-12 | OLON S.p.A. | Efficient method for the preparation of tofacitinib citrate |
| TW201718572A (zh) | 2015-06-24 | 2017-06-01 | 普林斯匹亞生物製藥公司 | 酪胺酸激酶抑制劑 |
| WO2017004134A1 (en) * | 2015-06-29 | 2017-01-05 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
| MA45547A (fr) | 2016-06-29 | 2019-05-08 | Principia Biopharma Inc | Formulations à libération modifiée à base de 2-[3-[4-amino-3-(2-fluoro-4-phénoxy-phényl)pyrazolo[3,4-d]pyrimidine-1-yl]pipéridine-1-carbonyl]-4-méthyl-4-[4-(oxétane-3-yl)pipérazine-1-yl]pent-2-ènenitrile |
| GB201617758D0 (en) | 2016-10-20 | 2016-12-07 | Almac Discovery Limited | Pharmaceutical compounds |
| TWI877239B (zh) | 2019-10-14 | 2025-03-21 | 美商普林斯匹亞生物製藥公司 | 藉由投予(R)-2-[3-[4-胺基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(氧呾-3-基)哌-1-基]戊-2-烯腈來治療免疫血小板減少症之方法 |
| JP2023511105A (ja) | 2020-01-22 | 2023-03-16 | プリンシピア バイオファーマ インコーポレイテッド | ２－［３－［４－アミノ－３－（２－フルオロ－４－フェノキシ－フェニル）－１ｈ－ピラゾロ［３，４－ｄ］ピリミジン－１－イル］ピペリジン－１－カルボニル］－４－メチル－４－［４－（オキセタン－３－イル）ピペラジン－１－イル］ペンタ－２－エンニトリルの結晶形態 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9911365A (pt) * | 1998-06-19 | 2001-03-13 | Pfizer Prod Inc | Compostos pirrolo[2,3-d]pirimidina |
| EP1382339B1 (en) * | 1999-12-10 | 2007-12-05 | Pfizer Products Inc. | Compositions containing pyrrolo ¬2,3-d pyrimidine derivatives |
| IL152771A0 (en) * | 2000-06-26 | 2003-06-24 | Pfizer Prod Inc | PYRROLO(2,3-d) PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS |
| US7301023B2 (en) * | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
| NZ539901A (en) * | 2002-11-26 | 2007-09-28 | Pfizer Prod Inc | Method of treatment of transplant rejection |
| EA008596B1 (ru) * | 2003-04-29 | 2007-06-29 | Пфайзер Инк. | 5,7-ДИАМИНОПИРАЗОЛО[4,3-d]ПИРИМИДИНЫ, ПОЛЕЗНЫЕ ПРИ ЛЕЧЕНИИ ГИПЕРТЕНЗИИ |
| JP2007512316A (ja) * | 2003-11-25 | 2007-05-17 | ファイザー・プロダクツ・インク | アテローム性動脈硬化症の治療方法 |
| AR054416A1 (es) * | 2004-12-22 | 2007-06-27 | Incyte Corp | Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas. |
| WO2007007919A2 (en) * | 2005-07-14 | 2007-01-18 | Astellas Pharma Inc. | Heterocyclic janus kinase 3 inhibitors |
| NL2000291C2 (nl) * | 2005-11-10 | 2009-02-17 | Pfizer Prod Inc | 1-(1-(2-ethoxyethyl)-3-ethyl-7-(4-methylpyridin-2-ylamino)-1H- pyrazool(4,3-d)pyrimidine-5-yl)piperidine-4-carbonzuur en zouten daarvan. |
| TW201111385A (en) * | 2009-08-27 | 2011-04-01 | Biocryst Pharm Inc | Heterocyclic compounds as janus kinase inhibitors |
| RU2013120966A (ru) * | 2010-10-08 | 2014-11-20 | Эббви Инк. | ФУРО[3,2-d]ПИРИМИДИНОВЫЕ СОЕДИНЕНИЯ |
-
2009
- 2009-07-31 US US13/057,100 patent/US20110165183A1/en not_active Abandoned
- 2009-07-31 RU RU2011105768/04A patent/RU2011105768A/ru not_active Application Discontinuation
- 2009-07-31 MX MX2011001259A patent/MX2011001259A/es unknown
- 2009-07-31 CA CA2732628A patent/CA2732628A1/en not_active Abandoned
- 2009-07-31 AU AU2009276420A patent/AU2009276420A1/en not_active Abandoned
- 2009-07-31 NZ NZ590922A patent/NZ590922A/xx not_active IP Right Cessation
- 2009-07-31 KR KR1020117004724A patent/KR20110050654A/ko not_active Withdrawn
- 2009-07-31 WO PCT/US2009/052449 patent/WO2010014930A2/en not_active Ceased
- 2009-07-31 EP EP09791064A patent/EP2324020A2/en not_active Withdrawn
- 2009-07-31 BR BRPI0916931A patent/BRPI0916931A2/pt not_active IP Right Cessation
- 2009-07-31 CN CN2009801396041A patent/CN102171211A/zh active Pending
- 2009-07-31 JP JP2011521361A patent/JP2011529918A/ja active Pending
-
2011
- 2011-02-01 IL IL210990A patent/IL210990A0/en unknown
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104059016A (zh) * | 2014-06-20 | 2014-09-24 | 湖南天地恒一制药有限公司 | 制备托法替布的中间体及所述中间体的制备方法 |
| CN107108630B (zh) * | 2014-08-29 | 2019-10-15 | 阳智化学（株） | 作为janus激酶抑制剂的被取代的n-(吡咯烷-3-基)-7h-吡咯并[2,3-d]嘧啶-4-胺 |
| CN107108630A (zh) * | 2014-08-29 | 2017-08-29 | 阳智化学（株） | 作为janus激酶抑制剂的被取代的n‑(吡咯烷‑3‑基)‑7h‑吡咯并[2,3‑d]嘧啶‑4‑胺 |
| CN105732637B (zh) * | 2014-12-30 | 2020-04-21 | 广东东阳光药业有限公司 | 杂芳化合物及其在药物中的应用 |
| CN105732637A (zh) * | 2014-12-30 | 2016-07-06 | 广东东阳光药业有限公司 | 杂芳化合物及其在药物中的应用 |
| RU2719477C2 (ru) * | 2015-06-22 | 2020-04-17 | Оно Фармасьютикал Ко., Лтд. | Соединение, ингибирующее brk |
| US11512087B2 (en) | 2015-06-22 | 2022-11-29 | Ono Pharmaceutical Co., Ltd. | BRK inhibitory compound |
| CN105622616A (zh) * | 2016-02-25 | 2016-06-01 | 上海雅本化学有限公司 | 一种4-氯吡咯并嘧啶的制备方法 |
| CN109970745A (zh) * | 2018-04-16 | 2019-07-05 | 深圳市塔吉瑞生物医药有限公司 | 取代的吡咯并三嗪类化合物及其药物组合物及其用途 |
| US11459334B2 (en) | 2018-04-16 | 2022-10-04 | Shenzhen Targetrx, Inc. | Substituted pyrrolo[2,1-f][1,2,4]triazines as KIT and/or PDGFR-α inhibitors |
| CN116768908A (zh) * | 2022-03-10 | 2023-09-19 | 石家庄迪斯凯威医药科技有限公司 | 一种含n多环化合物及其制备方法与用途 |
| CN116768908B (zh) * | 2022-03-10 | 2025-11-18 | 石家庄迪斯凯威医药科技有限公司 | 一种含n多环化合物及其制备方法与用途 |
| CN117164519A (zh) * | 2023-08-18 | 2023-12-05 | 杭州小蓓医药科技有限公司 | 一种l-肌肽的合成方法 |
| CN117534603A (zh) * | 2023-11-10 | 2024-02-09 | 江苏海悦康医药科技有限公司 | 一种托法替布中间体的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ590922A (en) | 2012-09-28 |
| EP2324020A2 (en) | 2011-05-25 |
| MX2011001259A (es) | 2011-03-15 |
| JP2011529918A (ja) | 2011-12-15 |
| IL210990A0 (en) | 2011-04-28 |
| RU2011105768A (ru) | 2012-09-10 |
| WO2010014930A2 (en) | 2010-02-04 |
| BRPI0916931A2 (pt) | 2015-11-24 |
| US20110165183A1 (en) | 2011-07-07 |
| KR20110050654A (ko) | 2011-05-16 |
| AU2009276420A1 (en) | 2010-02-04 |
| CA2732628A1 (en) | 2010-02-04 |
| WO2010014930A3 (en) | 2010-07-29 |
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