Array Biopharma Inc.

Allergan, Inc.

Intermune, Inc.

Loxo Oncology, Inc.

Eli Lilly and Company

Allergan Sales, Inc.

Japan Tobacco Inc.

Steven Wade Andrews

Yutong Jiang

Julia Haas

Gabrielle R Kolakowski

James F Blake

Kevin Ronald Condroski

Barbara J Brandhuber

Timothy S Kercher

Jeongbeob Seo

Li Ren

David A Moreno

Megan L McKenney

Shelley Allen

Gan Zhang

Adam Wade Cook

Tony P Tang

Andrew T Metcalf

Elizabeth A McFaddin

Julie Wurster

Oren T McNulty

Sean Douglas Aronow

Lily Huang

Michael E Garst

Robert M Burk

David Frederick Woodward

Thomas C Malone

Qian Zhao

Shane M Walls

Lawrence M Blatt

Hong-Woon Yang

Scott D Seiwert

Shannon L Winski

Clarence Eugene Hull, Iii

April L Kennedy

Ginelle A Ramann

Nisha Nanda

Edward H Wang

James Collier

Joshua H Bilenker

Mark Joseph Chicarelli

Xialing Guo

Erin Danielle Anderson

Thomas Combs Irvin

Manoj Kumar

Michael J Munchhof

Adam Golos

Leonid Beigelman

Bin Wang

Weidong Liu

Michael Lyon

Robert J Kaus

Jonathan J Hebert

Pierre Martin

Kevin W Hunt

Indrani W Gunawardana

Zhen Zhu

Paul Nichols

Allen A Thomas

Johnathan Alexander McLean

Andreas Schumacher

C Todd Eary

Tarek Sammakia

Elizabeth A Mcfaddin

Marta Pinto

Bradley Barnett

Tiphaine Mouret

Michael Alexander Pilkington-Miksa

Thomas Pierre Dino Pancaldi

Christopher Pierre Albert Jean Boldron

Eli M Wallace

Brad Owen Buckman

Kevin Koch

Ming Fai Chan

Takashi Inaba

Ellen Ruth Laird

Rui Xu

George T Topalov

Mark A Reynolds

John Peter Fischer

John A Josey

Martha E Rodriguez

Jay Bradford Fell

June Chen

Peter J Stengel

Todd S Gac

Charles Todd Eary

Shimiao Wang

Yvan Le Huerou

Stacey Spencer

Daniel John Watson

Bruno P Hache

Derrick Juengst

Gregory F Miknis

Achim H-p Krauss

Steven Mark Wenglowsky

Yoshikazu Hori

Makoto Shiozaki

Michael B Roof

Lisa A De Meese

Brian C Baer

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

Disclosed herein are compounds of formula I: or a pharmaceutically acceptable salt thereof, where the variables are as defined herein. These compounds are useful in treating RET associated cancers. Formulations containing the compounds of formula I and methods of making the compounds of formula I are also disclosed.

RET kinase inhibitors

Provided herein are RET kinase inhibitors according to the formula: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods for their use in the treatment of diseases that can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders. A, R, n, X, X, X, X, and Rhave the meanings given in the specification.

Compounds useful for inhibiting RET kinase

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 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

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

Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

Point mutations in TRK inhibitor-resistant cancer and methods relating to the same

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

Steven Wade Andrews