HETEROCYCLIC COMPOUNDS AND USES THEREOF
Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.
1 .- 53 . (canceled)
54 . A method of treating a disorder associated with PI3 kinase comprising administering to a subject in need thereof a compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein
W 1 is CR 3 ;
W 2 is CR 4 ;
W 3 is N;
W 4 is N;
W 5 is CR 7 ;
W 6 is CR 8 ;
R 1 and R 2 are independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocycloalkyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate,
R 3 is amido of formula —C(O)N(R) 2 , or —NHC(O)R, wherein R is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic; or wherein said (R) 2 groups taken together with the nitrogen to which they are attached form an optionally substituted 4-, 5-, 6-, or 7-membered ring, and
R 4 , R 7 and R 8 are each hydrogen.
55 . The method of claim 54 , wherein R 1 is hydrogen and R 2 is amino.
56 . The method of claim 55 , wherein R 2 is NH 2 .
57 . The method of claim 54 , wherein R 3 is amido of formula —C(O)N(R) 2 wherein said (R) 2 groups taken together with the nitrogen to which they are attached form an optionally substituted 4-, 5-, 6-, or 7-membered ring.
58 . The method claim 57 , wherein R 1 is hydrogen and R 2 is amino.
59 . The method claim 58 , wherein R 2 is NH 2 .
60 . The method of claim 59 , wherein R 3 is amido of formula —C(O)N(R) 2 wherein said (R) 2 groups taken together with the nitrogen to which they are attached form an optionally substituted 6-membered ring.
61 . The method of claim 60 , wherein the compound is
or pharmaceutically acceptable salt.
62 . The method of claim 54 , wherein the compound or pharmaceutically acceptable salt is
63 . The method of claim 54 , wherein the disorder is asthma, emphysema, bronchitis, psoriasis, allergy, anaphylaxis, rheumatoid arthritis, graft versus host disease, lupus erythematosus, psoriasis, restenosis, benign prostatic hypertrophy, diabetes, pancreatitis, proliferative glomerulonephritis, diabetes-induced renal disease, inflammatory bowel disease, atherosclerosis, eczema, scleroderma, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma, or ovarian, breast, lung, pancreatic, prostate, colon, gastric or epidermoid cancer.
64 . The method of claim 63 , wherein the disorder is lung cancer.
65 . The method of claim 64 , wherein the lung cancer is non-small cell lung cancer.
66 . The method of claim 64 , wherein the lung cancer is small cell lung cancer.
67 . The method of claim 63 , wherein the disorder is gastric cancer
68 . The method according to any one of claim 63 , 64 , 65 , 66 or 67 , wherein the compound is
or pharmaceutically acceptable salt.
69 . A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) comprising: contacting the PI3 kinase with a compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein
W 1 is CR 3 ;
W 2 is CR 4 ;
W 3 is N;
W 4 is N;
W 5 is CR 7 ;
W 6 is CR 8 ;
R 1 and R 2 are independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocycloalkyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate,
R 3 is amido of formula —C(O)N(R) 2 or —NHC(O)R, wherein R is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic; or wherein said (R) 2 groups taken together with the nitrogen to which they are attached form an optionally substituted 4-, 5-, 6-, or 7-membered ring, and
R 4 , R 7 and R 8 are each hydrogen.
70 . The method of claim 69 , wherein the compound is
or pharmaceutically acceptable salt.
71 . The method of claim 69 wherein said step of contacting comprises contacting a cell that expresses said PI3 kinase.
72 . The method of claim 69 wherein the PI3 kinase is PI3 kinase alpha.
73 . The method of claim 69 comprising administering a second therapeutic agent to the cell.
74 . The method of claim 69 wherein the contacting step takes place in vivo.
75 . The method of claim 69 wherein the contacting step takes place in vitro.