Benzoxepin PI3K inhibitor compounds and methods of use

US8952043B2 · kind B2 · utility

Assignee

• Genentech, Inc. · US

Inventors

• Nicole Blaquiere · South San Francisco, US
• Steven Do · San Jose, US
• Danette Dudley · Ann Arbor, US
• Adrian Folkes · Slough, GB
• Richard Goldsmith · Belmont, US
• Robert Heald · Harlow, GB
• Timothy Heffron · Burlingame, US
• Aleksandr Kolesnikov · Mill Valley, US
• Chudi Ndubaku · Oakland, US
• Alan G. Olivero · South San Francisco, US
• Stephen Price · Harlow, GB
• Steven Staben · South San Francisco, US
• BinQing Wei · Belmont, US

Key dates

• Filing date: Jan 23, 2014
• Grant date: Feb 10, 2015
• Expiry date: Jan 23, 2034

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D513/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and where (i) X1 is N and X2 is S, (ii) X1 is S and X2 is N, (iii) X1 is CR7 and X2 is S, (iv) X1 is S and X2 is CR7; (v) X1 is NR8 and X2 is N, (vi) X1 is N and X2 is NR8, (vii) X1 is CR7 and X2 is O, (viii) X1 is O and X2 is CR7, (ix) X1 is CR7 and X2 is C(R7)2, (x) X1 is C(R7)2 and X2 is CR7; (xi) X1 is N and X2 is O, or (xii) X1 is O and X2 is 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.