Inhibitors of c-Met and uses thereof

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein

L A is selected from

R A is selected from:

each of R A2 and R A6 is, independently, selected from hydrogen, halogen, —CN, —C(O)OR ++ , —C(O)R ++ , —C(O)N(R ++ ) 2 , —C(S)N(R ++ ) 2 , —C(NH)N(R ++ ) 2 , —OR ++ , —O(halo(C 1-4 aliphatic)), —OC(O)N(R ++ ) 2 , —SR ++ , —NO 2 , —N(R ++ ) 2 , —N(R ++ )C(O)(R ++ ), —N(R ++ )C(O)N(R ++ ) 2 , —N(R ++ )C(O)OR ++ , —N(R ++ )N(R ++ )C(O)R ++ , —N(R ++ )N(R ++ )C(O)N(R ++ ) 2 , —N(R ++ )N(R ++ )C(O)OR ++ , —N(R ++ )S(O) 2 N(R ++ ) 2 , —N(R ++ )S(O) 2 R ++ , —S(O) 2 R ++ , —S(O) 2 N(R ++ ) 2 , —S(O)R ++ , and C 1-4 aliphatic optionally substituted with substituents independently selected from halogen, —OR ++ , —SR ++ , —NO 2 , —CN, —N(R ++ ) 2 , or —N(R ++ )C(O)(R ++ );

R A3 , R A4 and the carbons to which they are bonded form a heterocyclyl or heteroaryl ring selected from:

wherein said heterocyclyl or heteroaryl ring is bonded to R A at the 4-position indicated;

each R A7 is, independently, hydrogen, —R o , —N(R o ) 2 , —NR o C(O)R o , —NR o C(O)N(R o ) 2 , —NR o CO 2 R o , —C(O)CH 2 C(O)R o , —CO 2 R o , —C(O)C(O)R o , —C(O)R o , —C(O)N(R o ) 2 , —S(O) 2 R o , —C(═S)N(R o ) 2 , —C(═NH)—N(R o ) 2 , or —(CH 2 ) y NHC(O)R o ;

each R A8 is, independently, hydrogen, halogen, —CN, —CO 2 R ++ , —C(O)R ++ , —C(O)N(R ++ ) 2 , —C(S)N(R ++ ) 2 , —C(NH)N(R ++ ) 2 , —OR ++ , —O(halo(C 1-4 aliphatic)), —OC(O)N(R ++ ) 2 , —SR ++ , —NO 2 , —N(R ++ ) 2 , —N(R ++ )C(O)(R ++ ), —N(R ++ )C(O)N(R ++ ) 2 , —N(R ++ )CO 2 R ++ , —N(R ++ )N(R ++ )C(O)R ++ , —N(R ++ )N(R ++ )C(O)N(R ++ ) 2 , —N(R ++ )N(R ++ )CO 2 R ++ , —N(R ++ )SO 2 N(R ++ ) 2 , —N(R ++ )SO 2 R ++ , —S(O) 2 R ++ , —SO 2 N(R ++ ) 2 , —S(O)R ++ , or a C 1-4 aliphatic group optionally substituted with substituents independently selected from halogen, —OR ++ , —SR ++ , —NO 2 , —CN, —N(R ++ ) 2 , or —N(R ++ )C(O)(R ++ );

each R A9 is, individually, hydrogen, F, Cl, C 1-4 aliphatic, or halo(C 1-4 aliphatic);

R A5 is hydrogen or R Ar ;

L B is a covalent bond or —N(R*)—;

R B is a 6-10 membered aryl ring; a 3-7 membered carbocyclic ring, a 5-10 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3-10 membered heterocyclyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each of said aryl, heteroaryl, or heterocyclyl rings is optionally substituted with up to five independent occurrences of R Ar ;

each R Ar is, independently, selected from halogen, —R o , —OR o , —SR o , —OC(O)(C 1-8 aliphatic), Ph optionally substituted with up to five independent occurrences of —R o , —CH 2 (Ph) optionally substituted with up to five independent occurrences of —R o , —(CH 2 ) y (Ph) optionally substituted with up to five independent occurrences of —R o , —NO 2 , —CN, —N(R o ) 2 , —NR o C(O)R o , —NR o C(O)N(R o ) 2 , —NR o C(O)OR o , —NR o NR o C(O)R o , —NR o NR o C(O)N(R o ) 2 , —NR o NR o C(O)OR o , —C(O)CH 2 C(O)R o , —C(O)OR o , —C(O)R o , —C(O)N(R o ) 2 , —OC(O)N(R o ) 2 , —S(O) 2 R o , —S(O) 2 N(R o ) 2 , —S(O)R o , —NR o S(O) 2 N(R o ) 2 , —NR o S(O) 2 R o , —C(S)N(R o ) 2 , —C(NH)N(R o ) 2 , and —(CH 2 ) y NHC(O)R o , wherein y is 1 to 4; or two adjacent R Ar groups taken together are 1,2-methylenedioxy or 1,2-ethylenedioxy;

each R ++ is, independently, hydrogen or C 1-4 aliphatic;

each R* is, independently, hydrogen or C 1-8 aliphatic optionally substituted with up to five independent occurrences of —NH 2 , —NH(C 1-4 aliphatic), —N(C 1-4 aliphatic) 2 , halogen, C 1-4 aliphatic, —OH, —O(C 1-4 aliphatic), —NO 2 , —CN, —C(O)OH, —C(O)O(C 1-4 aliphatic), —C(O)NH 2 , —C(O)NH(C 1-4 aliphatic), —C(O)N(C 1-4 aliphatic) 2 , —O(halo(C 1-4 aliphatic)), or halo(C 1-4 aliphatic); or two R* on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and

each R o is, independently, hydrogen, optionally substituted C 1-6 aliphatic, an unsubstituted 5-6 membered heteroaryl or heterocyclic ring, -Ph, or —O(Ph), wherein each substituent of said optionally substituted aliphatic of R o is, independently, —NH 2 , —NH(C 1-4 aliphatic), —N(C 1-4 aliphatic) 2 , halogen, C 1-4 aliphatic, —OH, —O(C 1-4 aliphatic), —NO 2 , —CN, —C(O)OH, —C(O)O(C 1-4 aliphatic), —C(O)NH 2 , —C(O)NH(C 1-4 aliphatic), —C(O)N(C 1-4 aliphatic) 2 , —O(halo(C 1-4 aliphatic)), or halo(C 1-4 aliphatic); or two R o on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

2. The compound according to claim 1 , wherein R B is selected from the group consisting of:

wherein

each of R B1 and R B2 is, independently, hydrogen or R Ar .

3. The compound according to claim 1 , wherein L B R B is selected from:

4. A compound according to claim 1 selected from

5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

6. A method of treating or lessening the severity of a proliferative disorder in a patient comprising the step of administering to said patient a therapeutically effective dose of a compound according to claim 1 or a composition according to claim 5 , wherein said proliferative disorder is gastric adenocarcinoma, gliobastoma, renal cancer, small cell lung carcinoma, colon cancer, colorectal cancer, prostate cancer, brain cancer, liver cancer, pancreatic cancer, or breast cancer.