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：US20210380609A1

公开(公告)日：2021-12-09

申请号：US17401892

申请日：2021-08-13

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

Inventor： Charles Todd EARY ,  Stacey SPENCER ,  Zack CRANE ,  Katelyn CHANDO ,  Sylvie ASSELIN ,  Weidong LIU ,  Mike WELCH ,  Adam COOK ,  Gabrielle R. KOLAKOWSKI ,  Andrew T. METCALF ,  David A. MORENO ,  Tony P. TANG

IPC: C07D519/00 ,  C07D471/04

Abstract: In some embodiments, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof, as disclosed herein.

公开(公告)号：US20210380582A1

公开(公告)日：2021-12-09

申请号：US17285997

申请日：2019-10-17

Applicant: Array BioPharma Inc.

Inventor： James Francis BLAKE ,  Mark Laurence BOYS ,  Mark Joseph CHICARELLI ,  Adam Wade COOK ,  Mohamed S. A. ELSAYED ,  Jay Bradford FELL ,  John Peter FISCHER ,  Ronald Jay HINKLIN ,  Oren Teague MCNULTY ,  Macedonio J. MEJIA ,  Martha E. RODRIGUEZ ,  Christina Elizabeth WONG

IPC: C07D471/04 ,  C07D519/00

Abstract: Compounds of Formula Ia or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative diseases. Methods of using compounds of Formula Ia or a stereoisomer, tautomer, prodrug 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

公开(公告)号：US11174273B2

公开(公告)日：2021-11-16

申请号：US16264194

申请日：2019-01-31

Applicant: Array BioPharma Inc.

Inventor： Eli Wallace ,  George Topalov ,  Joseph Lyssikatos ,  Alexandre Buckmelter ,  Qian Zhao

IPC: A61K31/517 ,  C07D498/10 ,  C07D239/94 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D498/04 ,  A61P35/00 ,  A61P29/00

Abstract: The invention includes methods of using compounds of Formula I as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as 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：US20210077493A1

公开(公告)日：2021-03-18

申请号：US16942094

申请日：2020-07-29

Applicant: Array BioPharma Inc.

Inventor： Donald T. Corson ,  Christopher M. Lindemann ,  Daniel J. Watson

IPC: A61K31/517 ,  A61K31/437 ,  A61P35/00 ,  C07D471/04 ,  A61K45/06

Abstract: Polymorphs of N4-(4-([1,2,4]triazolo[1,5 -a]pyridin-7-yloxy)-3 -methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine are provided herein. Processes for preparing the polymorphs and pharmaceutical composition comprising the polymorphs are also disclosed.

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：US20200317665A1

公开(公告)日：2020-10-08

申请号：US16835702

申请日：2020-03-31

Applicant: Array BioPharma Inc.

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

IPC: C07D471/04 ,  C07D401/14 ,  C07D513/10 ,  C07D471/10 ,  A61P35/00

Abstract: Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug 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.

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：US10729678B2

公开(公告)日：2020-08-04

申请号：US16512823

申请日：2019-07-16

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

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.