Certain chemical entities, compositions and methods
Chemical entities that modulate PI3 kinase activity, and chemical entities, pharmaceutical compositions, and methods of treatments of diseases and conditions associated with P13 kinase activity are described herein.
1. A compound of Formula VIII-A:
or a pharmaceutically acceptable salt thereof, wherein:
W d is
R a is hydrogen, halo, phosphate, urea, carbonate, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, or heterocycloalkyl;
R 11 is hydrogen, alkyl, halo, amino, amido, hydroxy, or alkoxy;
R 12 is hydrogen, alkyl, cyano, alkynyl, alkenyl, halo, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, amino, carboxylic acid, alkoxycarbonyl, or amido, and R 12 is optionally substituted;
B is alkyl, amino, heteroalkyl, cycloalkyl, heterocycloalkyl, or a moiety of Formula II:
W c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
q is an integer of 0, 1, 2, 3, or 4;
X is absent or is (CH(R 9 )) z —;
Y is absent, —O—, —S—, —S(═O)—, —S(═O) 2 —, —N(R 9 )—, —C(═O)(CHR 9 ) z —, —C(═O)—, —N(R 9 )C(═O)NH—, or —N(R 9 )C(R 9 ) 2 —, wherein no more than one of X or Y is absent;
each instance of z is independently an integer of 1, 2, 3, or 4;
R 1 is hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate;
R 2 is alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy or nitro;
R 3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamide, halo, cyano, hydroxyl, nitro, aryl, or heteroaryl;
R 5 and R 6 are independently hydrogen, C 1 -C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 -C 5 cycloalkyl, C 1 -C 4 heteroalkyl, C 1 -C 4 alkoxy, C 1 -C 4 amido, amino, acyl, C 1 -C 4 acyloxy, C 1 -C 4 sulfonamido, halo, cyano, hydroxy or nitro; and
each instance of R 9 is independently hydrogen, C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, or C 2 -C 10 heteroalkyl.
2. The compound of claim 1 , wherein W c is aryl or heterocycloalkyl.
3. The compound of claim 1 , wherein R 3 is alkyl.
4. The compound of claim 1 , wherein R 5 and R 6 are hydrogen.
5. The compound of claim 1 , wherein X is —(CH(R 9 )) z — and z is an integer of 1.
6. The compound of claim 1 , wherein Y is absent.
7. The compound of claim 1 , wherein R 12 is iodo, bromo,
8. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.