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 .- 59 . (canceled)
60 . A compound of Formula IX:
or a pharmaceutically acceptable salt thereof, wherein
W a 1 and W a 2 are independently CR 5 , S, N, or NR 4 , and W a 4 is independently CR 7 , S, N, or NR 4 wherein no more than two adjacent ring atoms are nitrogen or sulfur, and when W a 1 is S, one of W a 2 and W a 4 is N or NR 4 ;
W b 5 is CR 8 , N, or NR 8 ;
B is alkyl, amino, heteroalkyl, cycloalkyl, heterocycloalkyl, or a moiety of Formula II;
wherein W c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and
q is an integer of 0, 1, 2, 3, or 4;
W d is absent or is a heterocycloalkyl, aryl or heteroaryl moiety;
X is absent or is —(CH(R 9 )) z — and each instance of z independently is an integer of 1, 2, 3, or 4;
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)—, or —N(R 9 )—C(═O)NH—, —N(R 9 )C(R 9 ) 2 —, or —C(═O)—(CHR 9 ) z ;
R 1 is hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy or nitro;
R 2 is 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 4 is hydrogen, acyl, C 1 -C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 -C 5 cycloalkyl, or C 1 -C 4 heteroalkyl;
R 5 , R 7 , and R 8 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, acyl, C 1 -C 4 alkoxy, C 1 -C 4 amido, amino, 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 cycoakyl, or C 2 -C 10 heteroalkyl.
61 . The compound of claim 60 , wherein the compound has the structure of Formula XIII or X:
or a pharmaceutically acceptable salt thereof, wherein:
B is a moiety of Formula II;
wherein W c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and
q is an integer of 0, 1, or 2;
W d is
X is —(CH 2 )—;
Y is absent;
R 1 is hydrogen, fluoro, chloro, cyano, methyl, isopropyl, —CF 3 , methoxy, nitro;
R 2 is halo, cyano, hydroxy, or nitro;
R 4 is hydrogen or methyl;
R 5 is hydrogen or methyl;
R 7 is hydrogen or methyl;
R 11 is amino; and
R 12 is hydrogen, alkyl, alkynyl, alkenyl, halo, aryl, heteroaryl, heterocycloalkyl, or cycloalkyl.
62 . The compound of claim 60 , wherein R 12 is iodo, bromo,
63 . The compound of claim 60 , wherein the compound is
64 . A pharmaceutical composition comprising a compound of claim 60 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
65 . A method of treating a disorder comprising administering an effective amount of a compound of claim 60 to a subject, wherein the disorder is cancer, bone disorder, inflammatory disease, immune disease, nervous system disease, metabolic disease, respiratory disease, thrombosis, or cardiac disease.