Array Biopharma Inc.

Intermune, Inc.

Loxo Oncology, Inc.

Eli Lilly and Company

F. Hoffmann-la Roche Ag

Yutong Jiang

Julia Haas

Steven Wade Andrews

Gabrielle R Kolakowski

James F Blake

Kevin Ronald Condroski

Barbara J Brandhuber

Li Ren

David A Moreno

Jeongbeob Seo

Andrew T Metcalf

Timothy S Kercher

Gan Zhang

Shelley Allen

Elizabeth A McFaddin

Adam Wade Cook

Tony P Tang

Megan L McKenney

Oren T McNulty

Sean Douglas Aronow

Lily Huang

Shane M Walls

Qian Zhao

Ginelle A Ramann

Shannon L Winski

Mark Joseph Chicarelli

Hong-Woon Yang

James Collier

Lawrence M Blatt

April L Kennedy

Donghua Dai

Adam Golos

Bin Wang

Scott D Seiwert

Michael Lyon

Brett Joseph Prigaro

Robert J Kaus

Pierre Martin

Ronald Jay Hinklin

John Peter Fischer

Martha E Rodriguez

Mark Laurence Boys

Jay Bradford Fell

Charles Todd Eary

Paul Nichols

Weidong Liu

Macedonio J Mejia

Stacey Spencer

Allen A Thomas

Andreas Schumacher

C Todd Eary

Dean Russell Kahn

Tarek Sammakia

Christina Elizabeth Wong

Mohamed S A Elsayed

Bradley Barnett

Brett Prigaro

Leonid Beigelman

Brad Owen Buckman

Rui Xu

Mark A Reynolds

Peter J Stengel

Adam W Cook

Derrick Juengst

Bruno P Hache

Steven Mark Wenglowsky

Elizabeth A Mcfaddin

Oren Teague Mcnulty

David Fry

Kevin R Condroski

Steven D Andrews

Megan L Mckenney

Hailong Zhang

Timothy Krecher

HongWoon Yang

Bradley R Barnett

April Layne Kennedy

John Anthony Josey

Benjamin T Woodard

Peter John Stengel

Machender R Madduru

George Andrew Doherty

Timothy Kercher

Dean Kahn

Steven W Andrews

Oren T Mcknulty

Stephen S Andrews

Steven S Andrews

Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, X, X, X, X, 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.

Substituted pyrazolo[1,5-a]pyridine compounds as RET kinase inhibitors

Provided herein are compounds of the Formula (I): (I) and tautomers, stereoisomers and pharmaceutically acceptable salts and solvates thereof, wherein R, R, W, X, Y, Z, Ring A and (AA) 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.

Fused heterocyclic compounds as RET kinase inhibitors

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.

Protein tyrosine phosphatase inhibitors

Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X, X, Xand Xhave 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.

Substituted pyrazolo[1,5-A]pyrazine compounds as ret kinase inhibitors

Provided herein are compounds of the Formula I: or pharmaceutically acceptable salt or solvate thereof, wherein A, B, X, X, X, X, Ring D, E, R, R, 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.

Substituted pyrazolo[1,5-A]pyridine compounds as RET kinase inhibitors

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. 

Provided herein are compounds of the Formula I: [INSERT FORMULA I] and tautomers, stereoisomers and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2 and Ry 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. 

Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors

Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein Rand Rhave 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. 

Substituted pyrazolo[3,4-d]pyrimidines as RET kinase inhibitors

Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R, Rand Rhave 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. 

Substituted pyrazolyl[4,3-c]pyridine compounds as RET kinase inhibitors

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

Method of treatment using substituted pyrazolo[1,5-a] pyrimidine compounds

Process for preparing (S)&#x2014;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)&#x2014;N&#x2014;((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)&#x2014;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. 

Process for the preparation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide and salts thereof

Substituted pyrazolo[1,5-a]pyrazines as RET kinase inhibitors

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. 

Process for the preparation of pyrazolo[1,5-a]pyrimidines and salts thereof

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.

Bicyclic urea, thiourea, guanidine and cyanoguanidine compounds useful for the treatment of pain

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Boulder, CO, United States of America

Yutong Jiang