公开(公告)号：US20090192322A1

公开(公告)日：2009-07-30

申请号：US12319562

申请日：2009-01-08

申请人： Martin Quibell ,  James Nally ,  Lee Patient ,  Yikang Wang ,  Claudio Dagostin ,  John Paul Watts

发明人： Martin Quibell ,  James Nally ,  Lee Patient ,  Yikang Wang ,  Claudio Dagostin ,  John Paul Watts

IPC分类号： C07D491/048 ,  C07D307/28

CPC分类号： C07D493/04 ,  C07D307/28 ,  C07D491/04

摘要： The present invention relates to a process for preparing a compound of formula (Ia), (Ib), (Ic) or (Id), or a pharmaceutically acceptable salt, hydrate, solvate, complex or prodrug thereof, said process comprising the steps of: (A) (i) treating a compound of formula (IVa), where R48 is alkyl or tosyl, with an oxidising agent to form a compound of formula (Va); and (ii) converting said compound of formula (Va) to a compound of formula (Ia) or (Ic); or (B) (i) treating a compound of formula (IVb), where R48 is alkyl or tosyl, with an oxidising agent to form a compound of formula (Vb); and (ii) converting said compound of formula (Vb) to a compound of formula (Ib) or (Id).

摘要翻译： 本发明涉及制备式（Ia），（Ib），（Ic）或（Id）化合物或其药学上可接受的盐，水合物，溶剂化物，复合物或前药的方法，所述方法包括以下步骤： （A）（i）（i）用氧化剂处理其中R48为烷基或甲苯磺酰基的式（Ⅳa）化合物，形成式（Ⅴa）化合物; 和（ii）将所述式（Va）化合物转化为式（Ia）或（Ic）化合物; 或（B）（i）用氧化剂处理其中R48为烷基或甲苯磺酰基的式（Ⅳb）化合物以形成式（Ⅴb）化合物; 和（ii）将式（Vb）化合物转化为式（Ib）或（Id）化合物。

公开(公告)号：US08039641B2

公开(公告)日：2011-10-18

申请号：US12319562

申请日：2009-01-08

申请人： Martin Quibell ,  James Nally ,  Lee Patient ,  Yikang Wang ,  Claudio Dagostin ,  John Paul Watts

发明人： Martin Quibell ,  James Nally ,  Lee Patient ,  Yikang Wang ,  Claudio Dagostin ,  John Paul Watts

IPC分类号： C07D491/02

CPC分类号： C07D493/04 ,  C07D307/28 ,  C07D491/04

摘要： The present invention relates to a process for preparing a compound of formula (Ia), (Ib), (Ic) or (Id), or a pharmaceutically acceptable salt, hydrate, solvate, complex or prodrug thereof, said process comprising the steps of: (A) (i) treating a compound of formula (IVa), where R48 is alkyl or tosyl, with an oxidizing agent to form a compound of formula (Va); and (ii) converting said compound of formula (Va) to a compound of formula (Ia) or (Ic); or (B) (i) treating a compound of formula (IVb), where R48 is alkyl or tosyl, with an oxidizing agent to form a compound of formula (Vb); and (ii) converting said compound of formula (Vb) to a compound of formula (Ib) or (Id).

摘要翻译： 本发明涉及制备式（Ia），（Ib），（Ic）或（Id）化合物或其药学上可接受的盐，水合物，溶剂化物，复合物或前药的方法，所述方法包括以下步骤： （A）（i）（i）用氧化剂处理其中R48为烷基或甲苯磺酰基的式（Ⅳa）化合物以形成式（Ⅴa）化合物; 和（ii）将所述式（Va）化合物转化为式（Ia）或（Ic）化合物; 或（B）（i）用氧化剂处理其中R48为烷基或甲苯磺酰基的式（Ⅳb）化合物以形成式（Ⅴb）化合物; 和（ii）将式（Vb）化合物转化为式（Ib）或（Id）化合物。

公开(公告)号：US20110152244A1

公开(公告)日：2011-06-23

申请号：US13060154

申请日：2009-08-20

申请人： Gilbert Besong ,  Christopher Thomas Brain ,  Clinton A. Brooks ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Guo He ,  Ying Huo ,  Steven Howard ,  Yue Li ,  Yipin Lu ,  Paul Morteson ,  Troy Smith ,  Moo Sung ,  Steven Woodhead ,  Wojciech Wrona

发明人： Gilbert Besong ,  Christopher Thomas Brain ,  Clinton A. Brooks ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Guo He ,  Ying Huo ,  Steven Howard ,  Yue Li ,  Yipin Lu ,  Paul Morteson ,  Troy Smith ,  Moo Sung ,  Steven Woodhead ,  Wojciech Wrona

IPC分类号： C07D487/04 ,  A61K31/497 ,  A61K31/519 ,  A61K31/551 ,  A61K31/5377 ,  A61K31/501 ,  C12N9/99 ,  A61P35/04 ,  A61P29/00

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D487/08

摘要： The disclosed compounds relate to treatments and therapies for protein kinase-associated disorders. There is also a need for compounds useful in the treatment or prevention or amelioration of one or more symptoms of cancer, transplant rejections, and autoimmune diseases. Furthermore, there is a need for methods for modulating the activity of protein kinases, such as CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9, using the compounds provided herein.

摘要翻译： 所公开的化合物涉及蛋白激酶相关病症的治疗和疗法。 还需要可用于治疗或预防或改善癌症，移植排斥和自身免疫性疾病的一种或多种症状的化合物。 此外，需要使用本文提供的化合物调节蛋白激酶如CDK1，CDK2，CDK4，CDK5，CDK6，CDK7，CDK8和CDK9的活性的方法。

公开(公告)号：US09040545B2

公开(公告)日：2015-05-26

申请号：US13816555

申请日：2011-08-12

申请人： Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Boussard ,  Andrew Ratcliffe ,  Nigel Ramsden

发明人： Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Boussard ,  Andrew Ratcliffe ,  Nigel Ramsden

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  C07D487/04 ,  C07D519/00 ,  C07D491/107 ,  C07D498/08

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D491/107 ,  C07D498/08 ,  C07D519/00

摘要： The present invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

摘要翻译： 本发明涉及其中X1至X5，Y，Z1至Z3和R具有在说明书和权利要求书中引用的含义的式（I）化合物。 所述化合物可用作JAK抑制剂，用于治疗或预防免疫学，炎症，自身免疫，过敏性疾病和免疫介导的疾病。 本发明还涉及包含所述化合物的药物组合物，这些化合物的制备以及作为药物的用途。

公开(公告)号：US08685980B2

公开(公告)日：2014-04-01

申请号：US13060154

申请日：2009-08-20

申请人： Gilbert Ebai Besong ,  Christopher Thomas Brain ,  Clinton Alan Brooks ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Guo He ,  Ying Hou ,  Steven Howard ,  Yue Li ,  Yipin Lu ,  Paul Neil Mortenson ,  Troy D. Smith ,  Moo Je Sung ,  Steven John Woodhead ,  Wojciech Wrona ,  Bharat Lagu

发明人： Gilbert Ebai Besong ,  Christopher Thomas Brain ,  Clinton Alan Brooks ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Guo He ,  Ying Hou ,  Steven Howard ,  Yue Li ,  Yipin Lu ,  Paul Neil Mortenson ,  Troy D. Smith ,  Moo Je Sung ,  Steven John Woodhead ,  Wojciech Wrona ,  Bharat Lagu

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P35/00 ,  A61P29/00

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D487/08

摘要： The disclosed compounds relate to treatments and therapies for protein kinase-associated disorders. There is also a need for compounds useful in the treatment or prevention or amelioration of one or more symptoms of cancer, transplant rejections, and autoimmune diseases. Furthermore, there is a need for methods for modulating the activity of protein kinases, such as CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9, using the compounds provided herein.

摘要翻译： 所公开的化合物涉及蛋白激酶相关病症的治疗和疗法。 还需要可用于治疗或预防或改善癌症，移植排斥和自身免疫性疾病的一种或多种症状的化合物。 此外，需要使用本文提供的化合物调节蛋白激酶如CDK1，CDK2，CDK4，CDK5，CDK6，CDK7，CDK8和CDK9的活性的方法。

公开(公告)号：US09416136B2

公开(公告)日：2016-08-16

申请号：US14158358

申请日：2014-01-17

申请人： Gilbert Besong ,  Christopher Thomas Brain ,  Clinton A Brooks ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Guo He ,  Ying Hou ,  Steven Howard ,  Yue Li ,  Yipin Lu ,  Paul Mortenson ,  Troy Smith ,  Moo Je Sung ,  Steven Woodhead ,  Wojciech Wrona ,  Bharat Lagu

发明人： Gilbert Besong ,  Christopher Thomas Brain ,  Clinton A Brooks ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Guo He ,  Ying Hou ,  Steven Howard ,  Yue Li ,  Yipin Lu ,  Paul Mortenson ,  Troy Smith ,  Moo Je Sung ,  Steven Woodhead ,  Wojciech Wrona ,  Bharat Lagu

IPC分类号： A61K31/519 ,  A61P35/04 ,  C07D487/04 ,  C07D487/08

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D487/08

摘要： The disclosed compounds relate to treatments and therapies for protein kinase-associated disorders. There is also a need for compounds useful in the treatment or prevention or amelioration of one or more symptoms of cancer, transplant rejections, and autoimmune diseases. Furthermore, there is a need for methods for modulating the activity of protein kinases, such as CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9, using the compounds provided herein.

公开(公告)号：US20130190292A1

公开(公告)日：2013-07-25

申请号：US13816555

申请日：2011-08-12

申请人： Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Boussard ,  Andrew Ratcliffe ,  Nigel Ramsden

发明人： Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Boussard ,  Andrew Ratcliffe ,  Nigel Ramsden

IPC分类号： C07D487/04 ,  C07D491/107 ,  C07D498/08

CPC分类号： C07D487/04 ,  A61K31/519 ,  C07D491/107 ,  C07D498/08 ,  C07D519/00

摘要： The present invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

摘要翻译： 本发明涉及其中X1至X5，Y，Z1至Z3和R具有在说明书和权利要求书中引用的含义的式（I）化合物。 所述化合物可用作JAK抑制剂，用于治疗或预防免疫学，炎症，自身免疫，过敏性疾病和免疫介导的疾病。 本发明还涉及包含所述化合物的药物组合物，这些化合物的制备以及作为药物的用途。

公开(公告)号：US09242987B2

公开(公告)日：2016-01-26

申请号：US13503083

申请日：2010-10-19

申请人： Nigel Ramsden ,  Richard John Harrison ,  Sally Oxenford ,  Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Broussard ,  Andrew Ratcliffe

发明人： Nigel Ramsden ,  Richard John Harrison ,  Sally Oxenford ,  Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Broussard ,  Andrew Ratcliffe

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P29/00 ,  A61P37/00 ,  A61P37/08 ,  A61P41/00 ,  A61K31/541 ,  A61K31/5386 ,  A61K31/5377 ,  A61K31/496

CPC分类号： C07D487/04

摘要： The invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

摘要翻译： 本发明涉及式（I）的化合物，其中X 1至X 5，Y，Z 1至Z 3和R具有在说明书和权利要求书中引用的含义。 所述化合物可用作JAK抑制剂，用于治疗或预防免疫学，炎症，自身免疫，过敏性疾病和免疫介导的疾病。 本发明还涉及包含所述化合物的药物组合物，这些化合物的制备以及作为药物的用途。

公开(公告)号：US08598217B2

公开(公告)日：2013-12-03

申请号：US13266976

申请日：2010-04-30

申请人： Steven Howard ,  Paul Neil Mortenson ,  Steven Douglas Hiscock ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Gianni Chessari ,  Marc O'Reilly ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Young Shin Cho ,  Fan Yang ,  Christine Hiu-Tung Chen ,  Christopher Thomas Brain ,  Bharat Lagu ,  Yaping Wang ,  Sunkyu Kim ,  John Giraldes ,  Michael Joseph Luzzio ,  Lawrence Blas Perez

发明人： Steven Howard ,  Paul Neil Mortenson ,  Steven Douglas Hiscock ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Gianni Chessari ,  Marc O'Reilly ,  Miles Stuart Congreve ,  Claudio Dagostin ,  Young Shin Cho ,  Fan Yang ,  Christine Hiu-Tung Chen ,  Christopher Thomas Brain ,  Bharat Lagu ,  Yaping Wang ,  Sunkyu Kim ,  John Giraldes ,  Michael Joseph Luzzio ,  Lawrence Blas Perez

IPC分类号： A61K31/496 ,  A61K31/4545 ,  A61K31/4439 ,  A61K31/4725 ,  A61K31/4353 ,  A61K31/4178 ,  A61K31/4184 ,  A61P35/00 ,  C07D471/04 ,  C07D401/06 ,  C07D417/10 ,  C07D413/06 ,  C07D403/10

CPC分类号： C07D471/04 ,  C07D233/22 ,  C07D233/24 ,  C07D235/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  C07D487/04 ,  C07D519/00

摘要： The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N+—O− or CR3; Y is N, N+—O− or CR3a; R1 and R2 are independently selected from hydrogen and various substituents as defined in the claims; or R1 and R2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R3 is selected from hydrogen and various substituents; and R3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.

摘要翻译： 本发明提供式（I）化合物及其盐，互变异构体，溶剂化物和N-氧化物; 其中Q是CH或N; X是N，N + -O-或CR 3; Y是N，N + -O-或CR3a; R1和R2独立地选自氢和权利要求中定义的各种取代基; 或R 1和R 2与它们所连接的原子一起连接以形成任选取代的4至7个成员的碳环或杂环芳族或非芳族环; R3选自氢和各种取代基; 并且R 3a选自氢和权利要求中定义的各种取代基。 还提供含有式（I）化合物，制备化合物的方法和化合物的医疗用途的药物组合物。 式（I）化合物具有作为CDK激酶抑制剂的活性，并且可用于治疗尤其是增殖性疾病如癌症。

公开(公告)号：US20120252779A1

公开(公告)日：2012-10-04

申请号：US13503083

申请日：2010-10-19

申请人： Nigel Ramsden ,  Richard John Harrison ,  Sally Oxenford ,  Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Boussard ,  Andrew Ratcliffe

发明人： Nigel Ramsden ,  Richard John Harrison ,  Sally Oxenford ,  Kathryn Bell ,  Nelly Piton ,  Claudio Dagostin ,  Cyrille Boussard ,  Andrew Ratcliffe

IPC分类号： A61K31/519 ,  A61K31/5386 ,  A61K31/5377 ,  A61K31/496 ,  A61P41/00 ,  C07D487/04 ,  A61P37/00 ,  A61P29/00 ,  A61P37/08 ,  A61K31/541 ,  C07D498/08

CPC分类号： C07D487/04

摘要： The invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

摘要翻译： 本发明涉及式（I）的化合物，其中X 1至X 5，Y，Z 1至Z 3和R具有在说明书和权利要求书中引用的含义。 所述化合物可用作JAK抑制剂，用于治疗或预防免疫学，炎症，自身免疫，过敏性疾病和免疫介导的疾病。 本发明还涉及包含所述化合物的药物组合物，这些化合物的制备以及作为药物的用途。