公开(公告)号：US09902741B2

公开(公告)日：2018-02-27

申请号：US15632187

申请日：2017-06-23

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  Kevin Ronald Condroski ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski ,  Jeongbeob Seo ,  Hong-Woon Yang ,  Qian Zhao

IPC: C07D498/22 ,  C07D471/22 ,  C07D487/22

CPC classification number: C07D498/22 ,  A61K31/519 ,  C07D471/22 ,  C07D487/04 ,  C07D487/22 ,  C07D519/00

Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

公开(公告)号：US20180030548A1

公开(公告)日：2018-02-01

申请号：US15785174

申请日：2017-10-16

Applicant: Loxo Oncology, Inc. ,  Array BioPharma, Inc.

Inventor： Nisha Nanda ,  Josh H. Bilenker ,  James F. Blake ,  Gabrielle R. Kolakowski ,  Barbara J. Brandhuber ,  Steven W. Andrews

IPC: C12Q1/68 ,  A61K31/5025 ,  A61K31/519

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 point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

公开(公告)号：US09840519B2

公开(公告)日：2017-12-12

申请号：US15350888

申请日：2016-11-14

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  Kevin Ronald Condroski ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski ,  Jeongbeob Seo ,  Hong-Woon Yang ,  Qian Zhao

IPC: C07D498/22 ,  C07D471/22

CPC classification number: C07D498/22 ,  A61K31/519 ,  C07D471/22 ,  C07D487/04 ,  C07D487/22 ,  C07D519/00

Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

公开(公告)号：US09796723B2

公开(公告)日：2017-10-24

申请号：US15401792

申请日：2017-01-09

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  Julia Haas ,  Yutong Jiang ,  Gan Zhang

IPC: C07D487/04 ,  C07D519/00

CPC classification number: C07D487/04 ,  A61K31/5025 ,  A61K31/5377 ,  A61K31/541 ,  C07C51/412 ,  C07C53/18 ,  C07D471/04 ,  C07D519/00

Abstract: Methods for treating a disease or disorder selected from pain, cancer, inflammation, neurodegenerative disease, Typanosoma cruzi infection and osteolytic disease in a mammal, which comprise administering to said mammal a therapeutically effective amount of a compound of Formula I in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification.

公开(公告)号：US20170260589A1

公开(公告)日：2017-09-14

申请号：US15335378

申请日：2016-10-26

Applicant: Loxo Oncology, Inc. ,  The Regents of the University of Colorado, a body corporate ,  Array BioPharma, Inc.

Inventor： Nisha Nanda ,  Josh H. Bilenker ,  Robert C. Doebele ,  James F. Blake ,  Gabrielle R. Kolakowski ,  Barbara J. Brandhuber ,  Steven W. Andrews

IPC: C12Q1/68 ,  A61K31/519 ,  A61K31/5025

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.

公开(公告)号：US09718822B2

公开(公告)日：2017-08-01

申请号：US15401839

申请日：2017-01-09

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  Kevin Ronald Condroski ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski ,  Jeongbeob Seo ,  Hong-Woon Yang ,  Qian Zhao

IPC: C07D487/22 ,  A61K31/519 ,  C07D471/22 ,  C07D498/22

CPC classification number: C07D498/22 ,  A61K31/519 ,  C07D471/22 ,  C07D487/04 ,  C07D487/22 ,  C07D519/00

Abstract: Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

公开(公告)号：US20160228441A1

公开(公告)日：2016-08-11

申请号：US14846166

申请日：2015-09-04

Applicant: Array BioPharma, Inc.

Inventor： Julia Haas ,  Steven W. Andrews ,  Yutong Jiang ,  Gan Zhang

IPC: A61K31/519 ,  A61K45/06 ,  A61K31/5377 ,  A61K9/00

CPC classification number: C07D487/04 ,  A61K9/0053 ,  A61K31/519 ,  A61K31/5377 ,  A61K45/06 ,  A61P29/00 ,  C07D471/04 ,  C07D519/00

Abstract: Compounds useful in the synthesis of compounds for treating pain, cancer, inflammation, neurodegenerative disease or Typanosoma cruzi infection in a mammal.

Abstract translation: 用于合成用于治疗哺乳动物疼痛，癌症，炎症，神经变性疾病或克氏锥虫感染的化合物的化合物。

公开(公告)号：US11851434B2

公开(公告)日：2023-12-26

申请号：US17514684

申请日：2021-10-29

Applicant: Array BioPharma Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski ,  David A. Moreno ,  Li Ren ,  Shane M. Walls

IPC: A61K31/4985 ,  C07D487/04

CPC classification number: C07D487/04

Abstract: Provided herein are compounds of the Formula I:




and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 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：US11214571B2

公开(公告)日：2022-01-04

申请号：US16302312

申请日：2017-05-18

Applicant: Array BioPharma Inc. ,  Loxo Oncology, Inc.

Inventor： Mark Reynolds ,  Charles Todd Eary ,  Stacey Spencer ,  Derrick Juengst ,  Bruno Hache ,  Yutong Jiang ,  Julia Haas ,  Steven W. Andrews

IPC: C07D487/04

Abstract: Process for preparing (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a] pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide (formula I) or a salt thereof by reacting phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate or a similar derivative (formula 13) with (S)-pyrrolidin-3-ol (formula 14). Process for preparing phenyl(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3,3a-dihydropyrazolo[1,5-a]pyrimidin-3-yl)carbamate (formula 13) or a similar derivative by reduction of (R)-5-(2-(2,5-difluorophenyl) pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (formula 11) to (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (formula 12). Process for preparing (R)-2-(2,5-difluorophenyl)pyrrolidine(R)-2-hydroxysuccinate (formula 10) by treating (R)—N—((R)-1-(2,5-difluorophenyl)-3-(1,3-dioxan-2-yl)propyl)-2-methylpropane-2-sulfinamide (formula 19) with an acid and a reducing agent. (S)—N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, is a tyrosin kinase (TRK) inhibitor for trearing e.g. cancer.

公开(公告)号：US10724102B2

公开(公告)日：2020-07-28

申请号：US15335378

申请日：2016-10-26

Applicant: Loxo Oncology, Inc. ,  Array BioPharma, Inc.

Inventor： Nisha Nanda ,  Joshua H. Bilenker ,  James F. Blake ,  Gabrielle R. Kolakowski ,  Barbara J. Brandhuber ,  Steven W. Andrews

IPC: C12Q1/6886 ,  A61K31/5025 ,  A61K31/519 ,  G01N33/574

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 point mutations in NTRK1 and/or NTRK2 and/or NTRK3.