Array Biopharma Inc.

Loxo Oncology, Inc.

Eli Lilly and Company

Japan Tobacco Inc.

Intermune, Inc.

Mirati Therapeutics, Inc.

Julia Haas

Yutong Jiang

Steven Wade Andrews

Gabrielle R Kolakowski

James F Blake

Kevin Ronald Condroski

Li Ren

David A Moreno

Jeongbeob Seo

Andrew T Metcalf

Barbara J Brandhuber

Gan Zhang

Elizabeth A McFaddin

Tony P Tang

Shelley Allen

Megan L McKenney

Adam Wade Cook

Timothy S Kercher

Oren T McNulty

Sean Douglas Aronow

Shane M Walls

Lily Huang

Qian Zhao

Ginelle A Ramann

Hong-Woon Yang

James Collier

Mark Joseph Chicarelli

Shannon L Winski

Donghua Dai

Adam Golos

Allen A Thomas

Brett Joseph Prigaro

Brad Newhouse

Charles Todd Eary

Stacey Spencer

Dean Russell Kahn

Brett Prigaro

Leonid Beigelman

John Joseph Gaudino

Takashi Inaba

Ellen Ruth Laird

Mark A Reynolds

Christopher Ronald Smith

Matthew Arnold Marx

Scott D Seiwert

John David Lawson

Lawrence M Blatt

John Michael Ketcham

Aaron Craig Burns

Thomas P Bobinski

Derrick Juengst

Spencer Phillip Pajk

Bruno P Hache

Makoto Shiozaki

Yoshikazu Hori

Elizabeth A Mcfaddin

Oren Teague Mcnulty

Akira Suma

David Fry

Kevin R Condroski

Megan L Mckenney

Steven D Andrews

Hailong Zhang

HongWoon Yang

Hiroto Imai

Yuichi Shinozaki

Takafumi Matsuo

Andrew M Fryer

Atushi Sakai

Katsutaka Yasue

Nicole M Littmann

Timothy Krecher

Tamotsu Negoro

Makoto c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Shiozaki

Yuichi c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Shinozaki

Takashi c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Inaba

Nicole M Littman

Yoshikazu c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Mori

Katsutaka c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Yasue

Tamotsu c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Negoro

Akira c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Suma

Hiroto c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Imai

Takafumi c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Matsuo

Atushi c/o Japan Tobacco Inc Central Pharmaceutical Research Institute Sakai

Steven S Andrews

Stephen S Andrews

Oren T Mcknulty

Steven W Andrews

Dean Kahn

Timothy Kercher

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

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

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

Methods for inhibiting a ROS1 kinase with compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R, R, R, R, 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).

Macrocyclic compounds as ROS1 kinase inhibitors

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

Julia Haas