公开(公告)号：US10576080B2

公开(公告)日：2020-03-03

申请号：US15818082

申请日：2017-11-20

Applicant: Array BioPharma, Inc.

Inventor： Shenlin Huang ,  Xianming Jin ,  Zuosheng Liu ,  Daniel Poon ,  John Tellew ,  Yongqin Wan ,  Xing Wang ,  Yongping Xie

IPC: A61K31/506 ,  A61K31/4184 ,  A61K9/00 ,  C07D405/14 ,  A61K45/06 ,  C07D403/04 ,  C07D401/14

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of B-Raf.

公开(公告)号：US20190365763A1

公开(公告)日：2019-12-05

申请号：US16377514

申请日：2019-04-08

Applicant: Array BioPharma Inc.

Inventor： Shelley Allen ,  Steven W. Andrews ,  Kevin Ronald Condroski ,  Julia Haas ,  Lily Huang ,  Yutong Jiang ,  Timothy Kercher ,  Jeongbeob Seo

IPC: A61K31/519 ,  C07D519/00 ,  C07D487/04 ,  C07D453/02 ,  C07D471/22 ,  C07D498/22 ,  A61K31/5377

Abstract: Compounds of Formula I: and salts thereof in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

公开(公告)号：US10441581B2

公开(公告)日：2019-10-15

申请号：US15860894

申请日：2018-01-03

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 ,  A61K31/4545 ,  A61P1/00 ,  A61P35/00 ,  A61P35/02 ,  A61K31/444 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  A61P1/12

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：US10398683B2

公开(公告)日：2019-09-03

申请号：US15842715

申请日：2017-12-14

Applicant: Array BioPharma Inc.

Inventor： Christoph Max Krell ,  Marian Misun ,  Daniel Andreas Niederer ,  Werner Heinz Pachinger ,  Marie-Christine Wolf ,  Daniel Zimmermann ,  Weidong Liu ,  Peter J. Stengel ,  Paul Nichols

IPC: A61K31/4184 ,  A61K45/06 ,  A61K47/26 ,  A61K9/20 ,  C07D235/08 ,  C07D235/06 ,  A61K47/12 ,  A61K47/02 ,  C30B29/54 ,  C30B7/08 ,  A61K47/38 ,  A61K9/00

Abstract: The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound.

公开(公告)号：US20190218222A1

公开(公告)日：2019-07-18

申请号：US16302312

申请日：2017-05-18

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

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

IPC: C07D487/04

CPC classification number: 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：US20190216923A1

公开(公告)日：2019-07-18

申请号：US16244768

申请日：2019-01-10

Applicant: Array BioPharma Inc.

Inventor： Patrice A. Lee ,  David Chantry ,  Shannon L. Winski

IPC: A61K39/395 ,  A61P35/00 ,  A61K31/4184 ,  A61P35/04 ,  A61K9/00

CPC classification number: A61K39/3955 ,  A61K9/0019 ,  A61K31/4184 ,  A61K2039/54 ,  A61K2039/545 ,  A61P35/00 ,  A61P35/04

Abstract: This invention relates to a method of treating cancer by administering to a patient in need thereof, over a period of time, therapeutic agents that consist essentially of a MEK inhibitor which is binimetinib or a pharmaceutically acceptable salt thereof, and a PD-1 binding antagonist, to a patient in need thereof.

公开(公告)号：US20190211102A1

公开(公告)日：2019-07-11

申请号：US16244827

申请日：2019-01-10

Applicant: Array BioPharma Inc.

Inventor： Patrice A. Lee ,  David Chantry ,  Shannon L. Winski

IPC: C07K16/28 ,  A61P35/04 ,  A61K9/00 ,  A61K31/4439

CPC classification number: C07K16/2818 ,  A61K9/0019 ,  A61K9/0053 ,  A61K31/4439 ,  A61P35/04

Abstract: This invention relates to a method of treating cancer by administering a combination therapy comprising a combination of CSF-1R inhibitor, which is ARRY-382 or a pharmaceutically acceptable salt thereof, and a PD-1 binding antagonist, to a patient in need thereof.

公开(公告)号：US10329288B2

公开(公告)日：2019-06-25

申请号：US14913635

申请日：2014-08-21

Applicant: Genentech, Inc. ,  Array BioPharma Inc.

Inventor： Chong Han ,  Keena Green ,  Francis Gosselin ,  Michelangelo Scalone ,  Paul J. Nichols ,  Weidong Liu ,  Keith L. Spencer ,  Zackary D. Crane ,  Peter J. Stengel ,  Sagar Shakya

IPC: C07D471/04

Abstract: The invention provides processes of preparation thereof useful in the preparation of compounds that can be used as CHK1 inhibitors.

公开(公告)号：US10285993B2

公开(公告)日：2019-05-14

申请号：US15706062

申请日：2017-09-15

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C07D487/04 ,  C12Q1/48

Abstract: A novel crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US10258622B2

公开(公告)日：2019-04-16

申请号：US15452239

申请日：2017-03-07

Applicant: Array BioPharma, Inc.

Inventor： Daya Verma ,  Yogita Krishnamachari ,  Xiaohong Shen ,  Hanchen Lee ,  Ping Li ,  Rajinder Singh ,  LayChoo Tan

IPC: A61K31/506 ,  A61K9/20 ,  A61K9/28 ,  A61K9/48 ,  A61K9/00

Abstract: This invention relates to solid oral pharmaceutical formulations of (S)-methyl (1-((4-(3-(5-chloro-2-fluoro-3-(methyl-sulfonamido)phenyl)-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-yl)carbamate (COMPOUND A) and the use of these formulations for treating proliferative diseases, such as solid tumor diseases.