公开(公告)号：WO2018170381A1

公开(公告)日：2018-09-20

申请号：PCT/US2018/022833

申请日：2018-03-16

Applicant: ANDREWS, Steven W. ,  BLAKE, James F. ,  HAAS, Julia ,  KOLAKOWSKI, Gabrielle R.

Inventor： ANDREWS, Steven W. ,  BLAKE, James F. ,  HAAS, Julia ,  KOLAKOWSKI, Gabrielle R.

IPC: A61K31/395 ,  G01N33/574

Abstract: Methods for inhibiting a ROS1 kinase with compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R 2 , R 2a , R 3 , R 3a , and Z are as defined herein. The compounds and methods provided herein are useful in the treatment of cancer (e.g., ROS1-associated cancers as defined herein).

公开(公告)号：WO2018136661A1

公开(公告)日：2018-07-26

申请号：PCT/US2018/014279

申请日：2018-01-18

Applicant: ANDREWS, Steven W. ,  BLAKE, James F. ,  HAAS, Julia ,  JIANG, Yutong ,  KOLAKOWSKI, Gabrielle R. ,  MORENO, David A. ,  REN, Li ,  WALLS, Shane M.

Inventor： ANDREWS, Steven W. ,  BLAKE, James F. ,  HAAS, Julia ,  JIANG, Yutong ,  KOLAKOWSKI, Gabrielle R. ,  MORENO, David A. ,  REN, Li ,  WALLS, Shane M.

IPC: C07D487/04 ,  A61K31/4985 ,  A61P25/00 ,  A61P35/00

Abstract: Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X 1 , X 2 , X 3 and X 4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

公开(公告)号：WO2017075107A1

公开(公告)日：2017-05-04

申请号：PCT/US2016/058951

申请日：2016-10-26

Applicant: NANDA, Nisha ,  BILENKER, Josh H. ,  DOEBELE, Robert C. ,  BLAKE, James F. ,  KOLAKOWSKI, Gabrielle R. ,  BRANDHUBER, Barbara J. ,  ANDREWS, Steven W.

Inventor： NANDA, Nisha ,  BILENKER, Josh H. ,  DOEBELE, Robert C. ,  BLAKE, James F. ,  KOLAKOWSKI, Gabrielle R. ,  BRANDHUBER, Barbara J. ,  ANDREWS, Steven W.

IPC: A61K31/5025 ,  A61K31/519 ,  C12Q1/68 ,  A61P35/00 ,  G01N33/574

CPC classification number: C12Q1/6886 ,  A61K31/5025 ,  A61K31/519 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57492 ,  G01N2800/50 ,  G01N2800/52

Abstract: Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

Abstract translation: 本文提供治疗患有癌症的受试者的方法，选择用于患有癌症的受试者的治疗的方法，选择具有癌症的受试者的方法用于不包括Trk抑制剂的治疗 ，确定具有癌症的受试者对用Trk抑制剂治疗具有阳性反应的可能性的方法，预测患有癌症的受试者中Trk抑制剂功效的方法，确定受试者发展Trk的风险的方法 抑制剂抗性癌症的方法，以及基于来自受试者的样品的细胞的检测来确定受试者中Trk抑制剂抗性癌症的存在的方法，所述样品在NTRK1中具有至少一个点突变和/或 NTRK2和/或NTRK3。

公开(公告)号：WO2014078378A1

公开(公告)日：2014-05-22

申请号：PCT/US2013/069838

申请日：2013-11-13

Applicant: ARRAY BIOPHARMA INC. ,  ALLEN, Shelley ,  ANDREWS, Steven, Wade ,  BLAKE, James, F. ,  BRANDHUBER, Barbara, J. ,  CONDROSKI, Kevin, Ronald ,  HAAS, Julia ,  JIANG, Yutong ,  KERCHER, Timothy ,  KOLAKOWSKI, Gabrielle, R. ,  WINSKI, Shannon, L.

Inventor： ALLEN, Shelley ,  ANDREWS, Steven, Wade ,  BLAKE, James, F. ,  BRANDHUBER, Barbara, J. ,  CONDROSKI, Kevin, Ronald ,  HAAS, Julia ,  JIANG, Yutong ,  KERCHER, Timothy ,  KOLAKOWSKI, Gabrielle, R. ,  WINSKI, Shannon, L.

IPC: C07D403/12 ,  C07D401/14 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  A61K31/4025 ,  A61P29/00 ,  A61P35/00 ,  A61P25/28 ,  A61P27/02 ,  A61P13/08 ,  A61P13/06

CPC classification number: C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14

Abstract: Compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R 1 , R 2 , R a , R b , R c , R d , X, Ring B, and Ring C are as defined herein, and wherein Ring B moiety and the NH-C(=X)-NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.

Abstract translation: 式（I）的化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂合物或前药，其中R 1，R 2，R a，R b，R c，R d，X，环B和环C如本文所定义， 其中环B部分和NH-C（= X）-NH部分处于反式构型，是TrkA激酶的抑制剂，并且可用于治疗可用TrkA激酶抑制剂如疼痛，癌症， 炎症/炎性疾病，神经变性疾病，某些传染病，干燥综合征，子宫内膜异位症，糖尿病性周围神经病变，前列腺炎和骨盆疼痛综合征。

公开(公告)号：WO2014078372A1

公开(公告)日：2014-05-22

申请号：PCT/US2013/069827

申请日：2013-11-13

Applicant: ARRAY BIOPHARMA INC. ,  ALLEN, Shelley ,  ANDREWS, Steven Wade ,  BLAKE, James F. ,  BRANDHUBER, Barbara J. ,  JIANG, Yutong ,  KERCHER, Timothy ,  WINSKI, Shannon L.

Inventor： ALLEN, Shelley ,  ANDREWS, Steven Wade ,  BLAKE, James F. ,  BRANDHUBER, Barbara J. ,  JIANG, Yutong ,  KERCHER, Timothy ,  WINSKI, Shannon L.

IPC: C07D403/12 ,  A61K31/4025 ,  C07D471/04 ,  C07D487/04 ,  C07D207/14 ,  C07D513/04 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  A61P33/00 ,  A61P35/00

CPC classification number: C07D207/50 ,  C07C53/18 ,  C07D207/14 ,  C07D403/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

Abstract: Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R 1 , R 2 , R a , R b , R c , R d , X, Ring B, and Ring C are as defined herein, and wherein Ring B moiety and the NH-C(=X)-NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.

Abstract translation: 其中R1，R2，Ra，Rb，Rc，Rd，X，环B和环C如本文所定义的式I化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂合物或前药，其中环 B部分和NH-C（= X）-NH部分是反式构型，是TrkA激酶的抑制剂，可用于治疗可用TrkA激酶抑制剂治疗的疾病，例如疼痛，癌症，炎症/ 炎性疾病，神经变性疾病，某些传染病，干燥综合征，子宫内膜异位症，糖尿病性周围神经病变，前列腺炎和盆腔疼痛综合征。

公开(公告)号：WO2014078328A1

公开(公告)日：2014-05-22

申请号：PCT/US2013/069747

申请日：2013-11-12

Applicant: ARRAY BIOPHARMA INC. ,  ALLEN, Shelley ,  BLAKE, James F. ,  BRANDHUBER, Barbara J. ,  JIANG, Yutong ,  KOLAKOWSKI, Gabrielle R. ,  XU, Rui ,  WINSKI, Shannon L.

Inventor： ALLEN, Shelley ,  BLAKE, James F. ,  BRANDHUBER, Barbara J. ,  JIANG, Yutong ,  KOLAKOWSKI, Gabrielle R. ,  XU, Rui ,  WINSKI, Shannon L.

IPC: C07D401/14 ,  C07D231/40 ,  C07D231/44 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  A61K31/415 ,  A61P29/00 ,  A61P35/00 ,  A61P25/28

CPC classification number: C07D401/14 ,  C07D231/40 ,  C07D231/44 ,  C07D231/52 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04

Abstract: Compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.

Abstract translation: 式（I）的化合物或其立体异构体，互变异构体或其药学上可接受的盐，溶剂合物或前药，其中环A，环C和X如本文所定义，是TrkA激酶的抑制剂，并且可用于治疗可以 用TrkA激酶抑制剂治疗，如疼痛，癌症，炎症/炎性疾病，神经变性疾病，某些传染病，干燥综合征，子宫内膜异位症，糖尿病性周围神经病变，前列腺炎或骨盆疼痛综合征。

公开(公告)号：WO2008063202A2

公开(公告)日：2008-05-29

申请号：PCT/US2007002352

申请日：2007-01-30

Applicant: ARRAY BIOPHARMA INC ,  BLAKE JAMES F ,  BOYD STEVEN ,  DE MEESE JASON ,  GAUDINO JOHN J ,  MARLOW ALLISON L ,  SEO JEONGBEOB ,  THOMAS ALLEN A ,  TIAN HONGQI

Inventor： BLAKE JAMES F ,  BOYD STEVEN ,  DE MEESE JASON ,  GAUDINO JOHN J ,  MARLOW ALLISON L ,  SEO JEONGBEOB ,  THOMAS ALLEN A ,  TIAN HONGQI

CPC classification number: C07D495/04 ,  C07D519/00

Abstract: Compounds of Formula I and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula I and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract translation: 式I化合物及其药学上可接受的盐可用于抑制受体酪氨酸激酶和用于治疗由此介导的病症。 公开了使用式I化合物及其药学上可接受的盐在体外，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：WO2007103308A3

公开(公告)日：2007-09-13

申请号：PCT/US2007/005583

申请日：2007-03-06

Applicant: ARRAY BIOPHARMA INC. ,  GENENTECH, INC. ,  BLAKE, James F. ,  BOYD, Steven Armen ,  COHEN, Frederick ,  DE MEESE, Jason ,  FONG, Kin Chiu ,  GAUDINO, John J. ,  KAPLAN, Tomas ,  MARLOW, Allison L. ,  SEO, Jeongbeob ,  THOMAS, Allen A. ,  TIAN, Hongqi ,  YOUNG, Wendy B.

Inventor： BLAKE, James F. ,  BOYD, Steven Armen ,  COHEN, Frederick ,  DE MEESE, Jason ,  FONG, Kin Chiu ,  GAUDINO, John J. ,  KAPLAN, Tomas ,  MARLOW, Allison L. ,  SEO, Jeongbeob ,  THOMAS, Allen A. ,  TIAN, Hongqi ,  YOUNG, Wendy B.

IPC: C07D471/04 ,  A61K31/437 ,  A61P35/00

Abstract: Compounds of Formulas (Ia) and (Ib), and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, 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：WO2006117306A1

公开(公告)日：2006-11-09

申请号：PCT/EP2006/061781

申请日：2006-04-24

Applicant: F. HOFFMANN-LA ROCHE AG ,  BLAKE, James F. ,  FELL, Jay Bradford ,  FISCHER, John P. ,  HENDRICKS, Robert Than ,  SPENCER, Stacey Renee ,  STENGEL, Peter J.

Inventor： BLAKE, James F. ,  FELL, Jay Bradford ,  FISCHER, John P. ,  HENDRICKS, Robert Than ,  SPENCER, Stacey Renee ,  STENGEL, Peter J.

IPC: C07D417/04 ,  C07D417/14 ,  A61K31/416 ,  A61P31/12

CPC classification number: C07D417/06 ,  C07D417/04 ,  C07D417/14

Abstract: Compounds having the formula (I) wherein A, m and R 1 are herein defined are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for inhibiting hepatitis replication, processes for making the compounds and synthetic intermediates used in the process.

Abstract translation: 本文定义的具有式（I）的化合物，其中A，m和R 1是丙型肝炎病毒NS5b聚合酶抑制剂。 还公开了抑制肝炎复制的组合物和方法，制备该方法中使用的化合物和合成中间体的方法。

公开(公告)号：WO2020081848A1

公开(公告)日：2020-04-23

申请号：PCT/US2019/056786

申请日：2019-10-17

Applicant: ARRAY BIOPHARMA INC. ,  BLAKE, James F. ,  BOYS, Mark Laurence ,  CHICARELLI, Mark Joseph ,  COOK, Adam ,  ELSAYED, Mohamed S. A. ,  FELL, Jay B. ,  FISCHER, John P. ,  HINKLIN, Ronald Jay ,  MCNULTY, Oren T. ,  MEJIA, Macedonio J. ,  RODRIGUEZ, Martha E. ,  WONG, Christina E.

Inventor： BLAKE, James F. ,  BOYS, Mark Laurence ,  CHICARELLI, Mark Joseph ,  COOK, Adam ,  ELSAYED, Mohamed S. A. ,  FELL, Jay B. ,  FISCHER, John P. ,  HINKLIN, Ronald Jay ,  MCNULTY, Oren T. ,  MEJIA, Macedonio J. ,  RODRIGUEZ, Martha E. ,  WONG, Christina E.

IPC: C07D401/04 ,  C07D471/04 ,  C07D519/00 ,  A61P35/00 ,  A61K31/498 ,  A61K31/4985

Abstract: Compounds of Formula la or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative diseases in the view of their ability to inhibit SHP2. Methods of using compounds of Formula I or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, for in vitro , in situ , and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.