公开(公告)号：US08455497B2

公开(公告)日：2013-06-04

申请号：US12370175

申请日：2009-02-12

申请人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger ,  Ronald George Sherrill

发明人： Michael R. Hale ,  Roger Tung ,  Stephen Price ,  Robin David Wilkes ,  Wayne Carl Schairer ,  Ashley Nicholas Jarvis ,  Andrew Spaltenstein ,  Eric Steven Furfine ,  Vicente Samano ,  Istvan Kaldor ,  John Franklin Miller ,  Michael Stephen Brieger ,  Ronald George Sherrill

IPC分类号： C07D493/04 ,  A61K31/34 ,  A61K31/357 ,  A61K31/36 ,  A61P31/18 ,  C07C311/16 ,  C07C311/29

CPC分类号： C07D493/04 ,  A61K31/352 ,  A61K31/36 ,  A61K45/06 ,  C07D317/46 ,  A61K2300/00

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

公开(公告)号：US08343955B2

公开(公告)日：2013-01-01

申请号：US13477587

申请日：2012-05-22

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC分类号： A61K31/553

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

公开(公告)号：US20120283257A1

公开(公告)日：2012-11-08

申请号：US13553650

申请日：2012-07-19

申请人： Stewart James Baker ,  Paul John Goldsmith ,  Timothy Colin Hancox ,  Neil Anthony Pegg ,  Stephen Price ,  Stephen Joseph Shuttleworth ,  Sukhjit Sohal

发明人： Stewart James Baker ,  Paul John Goldsmith ,  Timothy Colin Hancox ,  Neil Anthony Pegg ,  Stephen Price ,  Stephen Joseph Shuttleworth ,  Sukhjit Sohal

IPC分类号： A61K31/5377 ,  A61P29/00

CPC分类号： C07D495/04

摘要： Thienopyrimidines of formula (Ia) or (Ib): wherein R1-R3 have any of the values described herein, and the pharmaceutically acceptable salt thereof have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase, in particular the p110 delta subtype, such as immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

摘要翻译： 式（Ia）或（Ib）的噻吩并嘧啶：其中R1-R3具有本文所述的任何值，并且其药学上可接受的盐具有作为PI3K抑制剂的活性，因此可用于治疗由异常细胞生长引起的疾病和障碍 ，与PI3激酶，特别是p110δ亚型相关的功能或行为，例如免疫疾病，心血管疾病，病毒感染，炎症，代谢/内分泌障碍和神经障碍。 还描述了合成化合物的方法。

公开(公告)号：US08258152B2

公开(公告)日：2012-09-04

申请号：US12664303

申请日：2008-06-11

申请人： Hazel Joan Dyke ,  Stephen Price ,  Karen Williams

发明人： Hazel Joan Dyke ,  Stephen Price ,  Karen Williams

IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D413/00

CPC分类号： C07D471/04

摘要： The invention relates to N-substituted azaindolyl compounds of Formula I with anti-cancer and/or anti-inflammatory activity and more specifically to N-substituted azaindolyl compounds which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

摘要翻译： 本发明涉及具有抗癌和/或抗炎活性的更优选的具有抗癌和/或抗炎活性的式I的N-取代的氮杂吲哚基化合物，更具体地涉及抑制MEK激酶活性的N-取代的阿魏酰基化合物。 本发明提供了可用于抑制异常细胞生长或治疗过度增殖性疾病或治疗哺乳动物炎性疾病的组合物和方法。 本发明还涉及将化合物用于体外，原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。

公开(公告)号：US20110190257A1

公开(公告)日：2011-08-04

申请号：US12999003

申请日：2009-07-01

申请人： Robert Andrew Heald ,  Philip Jackson ,  Joseph P. Lyssikatos ,  Stephen Price ,  Pascal Pierre Alexandre Savy

发明人： Robert Andrew Heald ,  Philip Jackson ,  Joseph P. Lyssikatos ,  Stephen Price ,  Pascal Pierre Alexandre Savy

IPC分类号： A61K31/397 ,  C07D471/02 ,  C07D231/56 ,  C07D277/62 ,  C07D275/06 ,  A61K31/437 ,  A61K31/416 ,  A61K31/428 ,  A61P35/00

CPC分类号： C07D231/56 ,  C07D275/04 ,  C07D403/12 ,  C07D405/12 ,  C07D471/04

摘要： The invention relates to bicyclic heterocycles of formulae I and II with anti-cancer and/or anti-inflammatory activity and more specifically with MEK kinase inhibitory activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth, treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

摘要翻译： 本发明涉及式I和II的双环杂环，其具有抗癌和/或抗炎活性，更具体地涉及MEK激酶抑制活性。 本发明提供了可用于抑制异常细胞生长，治疗过度增殖性疾病或治疗哺乳动物炎性疾病的组合物和方法。 本发明还涉及将化合物用于体外，原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。

公开(公告)号：US07923456B2

公开(公告)日：2011-04-12

申请号：US12432529

申请日：2009-04-29

申请人： Stephen Price ,  Robert Heald ,  Wendy Lee ,  Mark E. Zak ,  Joanne Frances Mary Hewitt

发明人： Stephen Price ,  Robert Heald ,  Wendy Lee ,  Mark E. Zak ,  Joanne Frances Mary Hewitt

IPC分类号： A61K31/44

CPC分类号： C07D471/04 ,  C07D235/00 ,  C07D401/04 ,  C07D487/04

摘要： The invention relates to imidazopyridines of formula I with anti-cancer and/or anti-inflammatory activity and more specifically to imidazopyridines which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

摘要翻译： 本发明涉及式I的咪唑并吡啶与抗癌和/或抗炎活性，更具体地涉及抑制MEK激酶活性的咪唑并吡啶类。 本发明提供了可用于抑制异常细胞生长或治疗过度增殖性疾病或治疗哺乳动物炎性疾病的组合物和方法。 本发明还涉及将化合物用于体外，原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。

公开(公告)号：US20110076292A1

公开(公告)日：2011-03-31

申请号：US12890812

申请日：2010-09-27

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC分类号： A61K31/553 ,  C07D498/04 ,  C07D491/044 ,  C07D498/14 ,  A61K31/4196 ,  A61K31/496 ,  A61K31/454 ,  A61K39/00 ,  A61P35/00 ,  A61P35/02 ,  A61P29/00 ,  A61P9/00 ,  A61P1/16 ,  A61P31/12 ,  A61P7/00 ,  A61P3/10

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式I的苯并氧氮杂化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物及其药学上可接受的盐，其中：Z1是CR1或N; Z2为CR2或N; Z3为CR3或N; Z4是CR4或N; B是与苯并氧杂环环稠合的吡唑基，咪唑基或三唑基环，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗由脂质激酶介导的癌症等疾病。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US07893085B2

公开(公告)日：2011-02-22

申请号：US11894345

申请日：2007-08-20

申请人： Pascal Pierre Savy ,  Stephen Price ,  Hazel Joan Dyke ,  John Gary Montana ,  Karen Williams ,  Mark S. Stanley ,  Liang Bao

发明人： Pascal Pierre Savy ,  Stephen Price ,  Hazel Joan Dyke ,  John Gary Montana ,  Karen Williams ,  Mark S. Stanley ,  Liang Bao

IPC分类号： C07D221/00 ,  A61K31/4365 ,  A61P35/00 ,  A61P29/00 ,  C07D241/00 ,  C07D487/04 ,  A61K31/519 ,  A61K31/5025

CPC分类号： C07D495/04

摘要： The invention relates to azabenzothiophenyl compounds of Formula I with anti-cancer and/or anti-inflammatory activity and more specifically to azabenzothiophenyl compounds which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

摘要翻译： 本发明涉及具有抗癌和/或抗炎活性的式I的氮杂苯并噻吩基化合物，更具体地涉及抑制MEK激酶活性的氮杂苯并噻吩基化合物。 本发明提供了可用于抑制异常细胞生长或治疗过度增殖性疾病或治疗哺乳动物炎性疾病的组合物和方法。 本发明还涉及将化合物用于体外，原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。

公开(公告)号：US07893060B2

公开(公告)日：2011-02-22

申请号：US12663823

申请日：2008-06-12

申请人： Timothy Colin Hancox ,  Neil Anthony Pegg ,  Mandy Christine Beswick ,  Toby Jonathan Blench ,  Elsa Amandine Dechaux ,  Janusz Jozef Kulagowski ,  Alan John Nadin ,  Stephen Price

发明人： Timothy Colin Hancox ,  Neil Anthony Pegg ,  Mandy Christine Beswick ,  Toby Jonathan Blench ,  Elsa Amandine Dechaux ,  Janusz Jozef Kulagowski ,  Alan John Nadin ,  Stephen Price

IPC分类号： A61K31/5377 ,  C07D413/14

CPC分类号： C07D513/04

摘要： Thiazolopyrimidines of formula (I): wherein W represents a thiazole ring; R1 and R2 form, together with the N atom to which they are attached, a group of the following formula (IIa): in which A is a ring system; m is 0, 1 or 2; R3 is H or C1-C6 alkyl; and R4 is an indole group which is unsubstituted or substituted; and the pharmaceutically acceptable salts thereof are inhibitors of PI3K and are selective for the p110δ isoform, which is a class Ia PD kinase, over both other class Ia and class Ib kinases. The compounds may be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

摘要翻译： 式（I）的噻唑并嘧啶：其中W表示噻唑环; R1和R2与它们所连接的N原子一起形成下式（IIa）的基团：其中A是环系; m为0,1或2; R3是H或C1-C6烷基; R4是未取代或取代的吲哚基; 其药学上可接受的盐是PI3K的抑制剂，并且对于其它1a类和1b类激酶对p110δ同种型是Ia Ia激酶的选择性。 该化合物可用于治疗与PI3激酶例如癌症，免疫疾病，心血管疾病，病毒感染，炎症，代谢/内分泌功能障碍和神经障碍相关的异常细胞生长，功能或行为引起的疾病和障碍。

公开(公告)号：US20100305096A1

公开(公告)日：2010-12-02

申请号：US12787613

申请日：2010-05-26

申请人： Georgette Castanedo ,  Bryan Chan ,  David Goldstein ,  Rama Kondru ,  Matthew Lucas ,  Wylie Palmer ,  Stephen Price ,  Brian Safina ,  Pascal Pierre Alexandre Savy ,  Eileen Mary Seward ,  Daniel P. Sutherlin ,  Zachary K. Sweeney

发明人： Georgette Castanedo ,  Bryan Chan ,  David Goldstein ,  Rama Kondru ,  Matthew Lucas ,  Wylie Palmer ,  Stephen Price ,  Brian Safina ,  Pascal Pierre Alexandre Savy ,  Eileen Mary Seward ,  Daniel P. Sutherlin ,  Zachary K. Sweeney

IPC分类号： A61K31/5377 ,  C07D495/04 ,  C07D471/04 ,  C07D473/16 ,  A61K31/541 ,  A61K31/55 ,  A61K31/551 ,  A61K31/553 ,  A61P35/00 ,  A61P37/00 ,  A61P9/00 ,  A61P31/12 ,  A61P29/00 ,  A61P3/00 ,  A61P5/00 ,  A61P25/00

CPC分类号： C07D513/04 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04

摘要： Formula I (Ia and Ib) compounds wherein (i) X1 is N and X2 is S, (ii) X1 is CR7 and X2 is S, (iii) X1 is N and X2 is NR2, or (iv) X1 is CR7 and X2 is O, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式（I）和（Ib）化合物，其中（i）X1为N，X 2为S，（ii）X1为CR7，X2为S，（iii）X1为N，X2为NR2，或（iv）X1为CR7， X 2为O，包括立体异构体，互变异构体，代谢物及其药学上可接受的盐，可用于抑制PI3K的δ同种型，以及用于治疗由脂质激酶如炎症，免疫学和癌症介导的病症。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。