Substituted quinazolines as kinase inhibitors
The present invention provides compounds of Formula I that modulate PI3 kinase activity and methods of treatment of diseases and conditions associated with PI3 kinase activity.
1. A compound of Formula II:
or a pharmaceutically acceptable salt thereof, wherein
W 4 is N;
R 1 is unsubstituted methyl or methyl substituted with one or more fluoro;
R 2 is aryl, or heteroaryl, each independently substituted with OH or halo;
R 4 is hydrogen; and
R 5 is hydrogen, alkyl, aryl or heteroaryl, wherein the alkyl, aryl or heteroaryl is optionally substituted;
or R 4 and R 5 , taken together with the nitrogen atom to which they are attached form an optionally substituted heteroaryl ring;
wherein, when a moiety is optionally substituted, substituents are each independently selected from R a , —OR b , amino, halo, cyano, nitro, oxo, acyl, alkoxycarbonyl, aminocarbonyl, —OCOR b ,—OCO 2 R a , —OCONR b R c , sulfanyl, sulfinyl, and sulfonyl;
each R a is independently C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, aryl, or heteroaryl;
each R b is independently hydrogen or C 1 -C 6 alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and
each R c is independently hydrogen or C 1 -C 4 alkyl; or
R b and R c together with the nitrogen to which they are attached form a heterocycloalkyl group.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is unsubstituted methyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl substituted with one or more fluoro.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is aryl, substituted at one or both meta positions.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a bicyclic aryl or bicyclic heteroaryl.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is alkyl, aryl, or heteroaryl, each of which is optionally substituted.
7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition of claim 7 wherein the composition is formulated as a solid, semi-solid, liquid, or aerosol dosage form.
9. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.