Kinase inhibitors and methods of use

1. A compound of Formula:

wherein

K is NR 31 R 32 , CH 3 , CH 2 F, CHF 2 , CF 3 , F, or H;

V′ is NH—R 1 or —NHCO—R 1 ;

W 1 and W 2 are N;

X 1 is S;

X 2 , X 3 , X 4 , and X 5 are independently N or CR 2 , wherein no more than two adjacent ring atoms are N and the total number of X 2 , X 3 , X 4 , and X 5 which are N is no more than 3;

R 1 is H, -L-C 1-10 alkyl, -L-C 3-8 cycloalkyl, or -L-heterocycloalkyl, each of which is unsubstituted or substituted by one or more independent R 3 substituents;

L is absent, C═O, —C(═O)O—, —C(═O) NR 31 —, —S(O)—, —S(O) 2 —, —S(O) 2 NR 31 —, or —NR 31 —;

each instance of R 2 is independently hydrogen, halo, —OH, —R 31 , —CF 3 , —OCF 3 , —OR 31 , —NR 31 R 32 , —C(O)R 31 , —CO 2 R 31 , —C(═O)NR 31 R 32 , —NO 2 , —CN, —S(O) 0-2 R 31 , —SO 2 NR 31 R 32 , —NR 31 C(═O)R 32 , —NR 31 C(═O)OR 32 , —NR 31 C(═O)NR 32 R 33 , —NR 31 S(O) 0-2 R 32 , —NR 31 C(═NR 32 )NR 33 R 32 , —NR 31 C(═NR 32 )OR 33 , —OC(═O)OR 33 , —OC(═O)NR 31 R 32 , C 1-10 alkyl, C 3-8 cycloalkyl, —C 2-10 alkenyl-, —C 2-10 alkynyl, —C 1-10 alkoxy, -heterocycloalkyl, aryl, hetaryl, or heteroalkyl;

each instance of R 3 is independently hydrogen, halo, or —OH; and

R 31 , R 32 , and R 33 , in each instance, is independently H, C 1-10 alkyl, —C 3-8 cycloalkyl, aryl, hetaryl, or heterocycloalkyl.

2. The compound of claim 1 , wherein the compound is of Formula:

Wherein K, V′, X 1 , W 1 , W 2 and R 1 are as defined in claim 1 .

3. The compound of claim 1 , R 1 is -L-C 1-10 alkyl, -L-C 3-8 cycloalkyl, or -L-heterocycloalkyl.

4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

5. A method of inhibiting mTorC1 and/or mTorC2 in a subject in need thereof, comprising administering an effective amount of a compound of claim 1 to said subject.

6. The method of claim 5 , wherein the subject in need thereof is suffering from bone disorder, inflammatory disease, immune disease, nervous system disease, metabolic disease, respiratory disease, cardiac disease, or a neoplastic condition.

7. The method of claim 5 , wherein the subject in need thereof is suffering from an autoimmune disorder.

8. The method of claim 5 , wherein the compound is used in conjunction with a second therapeutic agent.

9. The method of claim 5 , wherein the compound selectively inhibits both mTorC1 and mTorC2 activity relative to all type I phosphatidylinositol 3-kinases (PI3-kinase) consisting of PI3-kinase α, PI3-kinase β, PI3-kinase γ, and PI3-kinase δ.

10. The method of claim 5 , wherein the disease is cancer.

11. The method of claim 10 , wherein the cancer is selected from B cell lymphoma, T cell lymphoma, non small cell lung carcinoma, or leukemia.