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：US11472802B2

公开(公告)日：2022-10-18

申请号：US16962305

申请日：2019-01-18

Applicant: Array BioPharma Inc.

Inventor： Shane M. Walls ,  Li Ren ,  Ginelle A. Ramann ,  David A. Moreno ,  Andrew T. Metcalf ,  Elizabeth A. McFaddin ,  Gabrielle R. Kolakowski ,  James F. Blake ,  Donghua Dai ,  Julia Haas ,  Yutong Jiang ,  Dean Kahn

IPC: C07D471/04 ,  A61P35/00 ,  C07F9/6561

Abstract: Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2 and R3 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：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：US11091486B2

公开(公告)日：2021-08-17

申请号：US16345571

申请日：2017-10-26

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

Inventor： Qian Zhao ,  Stacey Spencer ,  Yutong Jiang ,  Julia Haas ,  Charles Todd Eary

IPC: A61P25/00 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/22 ,  A61K31/519

Abstract: In some embodiments, provided herein are processes for preparing a compound of Formula C or a salt thereof, as disclosed herein. In some embodiments, provided herein is a compound of Formula I or a pharmaceutically acceptable salt, solvate or hydrate thereof. In some embodiments, provided herein is a solid form of the compound, such as a crystalline form of the compound crystalline Form I.

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：US20200262837A1

公开(公告)日：2020-08-20

申请号：US16868258

申请日：2020-05-06

Applicant: Mirati Therapeutics, Inc. ,  Array BioPharma Inc.

Inventor： Matthew Arnold Marx ,  Thomas P. Bobinski ,  Aaron Craig Burns ,  John Gaudino ,  Julia Haas ,  John Michael Ketcham ,  John David Lawson ,  Brad Newhouse ,  Spencer Pajk ,  Christopher Ronald Smith ,  Tony P. Tang

IPC: C07D471/04 ,  C07D491/08 ,  A61P35/00

Abstract: The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

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：US20190270743A1

公开(公告)日：2019-09-05

申请号：US16412091

申请日：2019-05-14

Applicant: Mirati Therapeutics, Inc. ,  Array BioPharma Inc.

Inventor： Matthew Arnold Marx ,  Thomas P. Bobinski ,  Aaron Craig Burns ,  John Gaudino ,  Julia Haas ,  John Michael Ketcham ,  John David Lawson ,  Brad Newhouse ,  Spencer Pajk ,  Christopher Ronald Smith ,  Tony P. Tang

IPC: C07D471/04 ,  C07D519/00 ,  A61P35/00

Abstract: The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

公开(公告)号：US20190211017A1

公开(公告)日：2019-07-11

申请号：US16044653

申请日：2018-07-25

Applicant: Array BioPharma Inc.

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

IPC: C07D487/04 ,  A61K31/519 ,  A61P29/00 ,  A61K31/5377 ,  C07D471/04 ,  A61K45/06 ,  A61K9/00 ,  C07D519/00

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