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：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：US20120101064A1

公开(公告)日：2012-04-26

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 Grialdes ,  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 Grialdes ,  Michael Joseph Luzzio ,  Lawrence Blas Perez

IPC分类号： A61K31/675 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/4545 ,  C07D413/06 ,  A61K31/5377 ,  C07D417/10 ,  A61K31/427 ,  C07D403/10 ,  A61K31/4178 ,  C07D409/10 ,  C07D401/06 ,  A61K31/4725 ,  A61K31/551 ,  C07D471/04 ,  A61K31/437 ,  C07F9/6561 ,  A61P35/00 ,  A61P35/02 ,  C07D401/14

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：US20100004243A1

公开(公告)日：2010-01-07

申请号：US12373659

申请日：2007-07-13

申请人： Miles Stuart Congreve ,  Adrian Liam Gill ,  Steven Howard ,  Paul Neil Mortenson ,  Gillbert Ebai Besong

发明人： Miles Stuart Congreve ,  Adrian Liam Gill ,  Steven Howard ,  Paul Neil Mortenson ,  Gillbert Ebai Besong

IPC分类号： A61K31/5377 ,  C07D417/14 ,  C07D401/14 ,  C07D413/14 ,  A61K31/454 ,  A61K31/437 ,  A61K31/496 ,  A61K31/4375 ,  A61P35/00 ,  C12N9/99

CPC分类号： C07D417/12 ,  C07D401/12 ,  C07D401/14 ,  C07D513/04

摘要： The invention provides a cyclin dependent kinase (e.g. cdk-4 kinase) inhibitor of the formula (I) or a salt, tautomer, solvate or N-oxide thereof; wherein R1 is an optionally substituted monocyclic or bicyclic aryl or heteroaryl group containing 0-2 heteroatoms selected from O, N and S wherein the optional substituents are selected from halogen, C1-4 alkyl, C1-4 alkoxy, C3-4 cycloalkyl and cyano, and wherein the C1-4 alkyl and C1-4 alkoxy groups are each optionally further substituted by C1-2 alkoxy or one or more halogen atoms; and E is a group E1, E2, E3 or E4: formulae E1, E2, E3, E4 wherein n, q, A5 B, T, U, V, W, Z, R2, R5, R6 and R7 are as defined in the claims.

摘要翻译： 本发明提供了式（I）的细胞周期蛋白依赖性激酶（例如cdk-4激酶）抑制剂或其盐，互变异构体，溶剂合物或N-氧化物; 其中R 1是含有0-2个选自O，N和S的杂原子的任选取代的单环或双环芳基或杂芳基，其中任选的取代基选自卤素，C 1-4烷基，C 1-4烷氧基，C 3-4环烷基和氰基 并且其中所述C 1-4烷基和C 1-4烷氧基各自任选进一步被C 1-2烷氧基或一个或多个卤素原子取代; 并且E是E1，E2，E3或E4基团：式E1，E2，E3，E4其中n，q，A5B，T，U，V，W，Z，R2，R5，R6和R7如 索赔。