Genentech, Inc.

F. Hoffmann-la Roche Ag

Hoffmann-la Roche Inc.

Curis, Inc.

Piramed Limited

Chiron Corporation

Genetech, Inc.

Richard A Goldsmith

Alan G Olivero

Daniel P Sutherlin

Adrian Folkes

Bing-Yan Zhu

Steven T Staben

Tim Heffron

Tracy Bayliss

Steven Huy Do

Aleksandr Kolesnikov

Georgette M Castanedo

Simon Mathieu

Janet Gunzner

Irina Chuckowree

Nan Chi Wan

Stephen Colin Price

Robert Andrew Heald

Chudi Obioma Ndubaku

Timothy Heffron

Michael Siu

Nicole Blaquiere

Danette Dudley

Shumei Wang

Kirk D Robarge

Vickie H Tsui

John A Flygare

Dean R Artis

Christian Wiesmann

BinQing Wei

Aihe Zhou

Stephen Joseph Shuttleworth

Dane A Goff

Ronald N Zuckermann

Zhonghua Pei

Daniel Fred Ortwine

Sally Oxenford

Paul Goldsmith

Neil Pegg

Jennafer Dotson

Yan Zhu

Richard Pastor

Thomas E Rawson

Binqing Wei

Kimberly Malesky

Tim Hancox

Michael S Dina

Stephen Shuttleworth

Ignacio Aliagas-Martin

Regina A Munroe

Kenneth J Weese

Simon C Ng

Michael F T Koehler

Reyna J Simon

Kerry L Spear

Barbara O Scott

Lutz Richter

Janet Gunzer-Toste

Charles K Marlowe

Aaron C Sigmund

Yazhong Pei

Jason Burch

Adrian J Folkes

Irina Cchuckowree

Janet Gunzer

Bing-Yang Zhu

Christian Weismann

Compounds of Formulae Ia, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Pharmaceutical compounds

Compounds of Formulas Ia-d where X is S or O, mor is a morpholine group, and Ris a monocyclic heteroaryl group, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for modulating the activity of lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia-d for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Phosphoinositide 3-kinase inhibitor compounds and methods of use

Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Benzopyran and benzoxepin PI3K inhibitor compounds and methods of use

Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Zis CRor N; Zis CRor N; Zis CRor N; Zis CRor N; and where (i) Xis N and Xis S, (ii) Xis S and Xis N, (iii) Xis CRand Xis S, (iv) Xis S and Xis CR; (v) Xis NRand Xis N, (vi) Xis N and Xis NR, (vii) Xis CRand Xis O, (viii) Xis O and Xis CR, (ix) Xis CRand Xis C(R), (x) Xis C(R)and Xis CR; (xi) Xis N and Xis O, or (xii) Xis O and Xis N, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Benzoxepin PI3K inhibitor compounds and methods of use

Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomer solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Compounds of Formulae Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 

4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene compounds

The invention provides novel inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A is a carbocycle or heterocycle; X is alkylene, NRC(O), NRC(S), NRC(NH), NRSO, NRSO, NRC(O)NH, NRC(S)NH, C(O)NR, C(S)NR, C(NH)NR, NRPO or NRPO(OH) wherein Ris H or alkyl; Ris selected from the group consisting of alkyl, cycloalkyl, aryl or a heterocycle each of which is optionally substituted with hydroxy, halogen, amino, nitro, alkyl, acyl, alkylsulfonyl or alkoxy; Ris halogen, hydroxy, alkyl, acyl or alkoxy each optionally substituted with hydroxy, halogen, amino, nitro, alkyl, acyl, alkylsulfonyl or alkoxy; Ris halogen, hydroxy, alkyl, acyl or alkoxy each optionally substituted with hydroxy, halogen, amino, nitro, alkyl, acyl, alkylsulfonyl or alkoxy; m is 0-3; n is 0-3; and salts and solvates thereof. The invention also provides methods of using these compounds for therapy and/or prophylaxis in a mammal of hyperproliferative diseases and angiogenesis mediated diseases due to their activity for inhibiting the hedgehog signaling pathway.

Quinoxaline inhibitors of the hedgehog signalling

The invention provides inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein ring A, ring B, R, R, R, R, R, m and n are as defined herein.

Bisamide inhibitors of hedgehog signaling

Growing community of inventors

Daly City, CA, United States of America

Richard A Goldsmith