公开(公告)号：US10889589B2

公开(公告)日：2021-01-12

申请号：US16415575

申请日：2019-05-17

Applicant: Array BioPharma Inc.

Inventor： Shelley Allen ,  Steven Wade Andrews ,  James F. Blake ,  Barbara J. Brandhuber ,  Julia Haas ,  Yutong Jiang ,  Timothy Kercher ,  Gabrielle R. Kolakowski ,  Allen A. Thomas ,  Shannon L. Winski

IPC: C07D401/14 ,  C07D405/14 ,  C07D403/14 ,  C07D491/048 ,  C07D231/40 ,  C07D231/54 ,  C07D401/12 ,  C07D403/02 ,  C07D403/04 ,  C07D405/12 ,  C07D413/12 ,  C07D453/02 ,  C07D231/52 ,  C07D231/56 ,  C07D401/04 ,  C07D409/14 ,  C07D471/08

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 and pelvic pain syndrome.

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.

公开(公告)号：US10688100B2

公开(公告)日：2020-06-23

申请号：US16199875

申请日：2018-11-26

Applicant: Array BioPharma Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Julia Haas ,  Gabrielle R. Kolakowski

IPC: A61K31/529 ,  A61K31/519 ,  A61K45/06 ,  G01N33/574 ,  A61P35/00 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/675

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, R2, R2a, R3, R3a, 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：US10584124B2

公开(公告)日：2020-03-10

申请号：US16156880

申请日：2018-10-10

Applicant: Array BioPharma Inc.

Inventor： Andrew T. Metcalf ,  David Fry ,  Elizabeth A. McFaddin ,  Gabrielle R. Kolakowski ,  Julia Haas ,  Tony P. Tang ,  Yutong Jiang

IPC: C07D471/08 ,  A61P35/00 ,  A61K9/00 ,  C07D471/04

Abstract: Provided herein are compound of Formula I-IV and pharmaceutically acceptable salts thereof which exhibit rearranged during transfection (RET) kinase inhibition. In particular, provided herein are novel crystalline forms of 4-(6-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)pyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula I), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula II), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-(6-methoxynicotinoyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula III), 6-(2-hydroxy-2-methylpropoxy)-4-(6-(4-hydroxy-4-(pyridin-2-ylmethyl)piperidin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile (Formula IV), and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds, processes for making the compounds, and the use of the compounds in therapy. More particularly, the application relates to novel crystalline forms of Formula I-IV and pharmaceutically acceptable salts thereof useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.

公开(公告)号：US10370727B2

公开(公告)日：2019-08-06

申请号：US15785174

申请日：2017-10-16

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

公开(公告)号：US20190151322A1

公开(公告)日：2019-05-23

申请号：US16199818

申请日：2018-11-26

Applicant: Array BioPharma Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Julia Haas ,  Gabrielle R. Kolakowski

IPC: A61K31/529 ,  A61K31/496 ,  A61K31/675 ,  A61K31/4545 ,  A61P35/00

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, R2, R2a, R3, R3a, 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：US10174028B2

公开(公告)日：2019-01-08

申请号：US15860849

申请日：2018-01-03

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Mark J. Chicarelli ,  Adam Golos ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski

IPC: C07D471/04 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/499 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D519/00

Abstract: Provided herein are compounds of the General 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：US10144734B2

公开(公告)日：2018-12-04

申请号：US15858929

申请日：2017-12-29

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  Sean Aronow ,  James F. Blake ,  Barbara J. Brandhuber ,  James Collier ,  Adam Cook ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski ,  Elizabeth A. McFaddin ,  Megan L. McKenney ,  Oren T. McNulty ,  Andrew T. Metcalf ,  David A. Moreno ,  Ginelle A. Ramann ,  Tony P. Tang ,  Li Ren ,  Shane M. Walls

IPC: C07D471/04 ,  A61K31/4162 ,  A61P1/00 ,  A61P35/00

Abstract: Provided herein are compounds of the Formula I: or pharmaceutically acceptable salt or solvate thereof, wherein A, B, X1, X2, X3, X4, Ring D, E, Ra, Rb, n and m 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 RET-associated diseases and disorders.

公开(公告)号：US10137124B2

公开(公告)日：2018-11-27

申请号：US15860852

申请日：2018-01-03

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  Sean Aronow ,  James F. Blake ,  Barbara J. Brandhuber ,  Adam Cook ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski ,  Elizabeth A. McFaddin ,  Megan L. McKenney ,  Oren T. McNulty ,  Andrew T. Metcalf ,  David A. Moreno ,  Tony P. Tang ,  Li Ren

IPC: A61K31/437 ,  A61K31/496 ,  C07D471/04 ,  A61P1/12 ,  A61P35/04 ,  C07D519/00 ,  A61P35/02 ,  A61P35/00 ,  A61K31/444 ,  A61K31/4985 ,  A61K31/4995 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  A61K31/551

Abstract: Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, X1, X2, X3, X4, Ring D, and E 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 RET-associated diseases and disorders.

公开(公告)号：US20180186790A1

公开(公告)日：2018-07-05

申请号：US15858658

申请日：2017-12-29

Applicant: Array BioPharma, Inc.

Inventor： Steven W. Andrews ,  James F. Blake ,  Mark J. Chicarelli ,  Adam Golos ,  Julia Haas ,  Yutong Jiang ,  Gabrielle R. Kolakowski

IPC: C07D471/04 ,  A61K31/55 ,  A61K45/06 ,  A61K31/499 ,  A61K31/444 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/497 ,  C07D519/00 ,  A61K31/506 ,  A61K31/4545

CPC classification number: C07D471/04 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/499 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K45/06 ,  C07D519/00

Abstract: Provided herein are compounds of the General 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.