Tetrazolones as inhibitors of fatty acid synthase

Abstract

Provided herein are tetrazolone FASN inhibitors of the formula (I): or a pharmaceutically acceptable form thereof, wherein the variables R A , R B and R C are defined herein. Also provided herein are pharmaceutical compositions of the compounds provided herein as well as methods of their use for the treatment of various disorders such as hyperproliferative disorders, inflammatory disorders, obesity-related disorders and microbial infections.

1 - 41 . (canceled) 
     
     
         42 . A method of treating prostate cancer comprising administering to a subject a therapeutically effective amount of a FASN inhibitor. 
     
     
         43 . The method of  claim 42 , wherein the FASN inhibitor is a compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof; 
       
       wherein:
 R A  is selected from C 6-14  aryl and 5-14 membered heteroaryl; 
 R B  is selected from C 6-14  aryl and 5-14 membered heteroaryl; 
 R C  is selected from —OH, —OR C1 , —ON(R C2 ) 2 , —N(R C2 ) 2 , —C(═O)R C1 , —CHO, —CO 2 R C1 , —C(═O)N(R C2 ) 2 , —C(═NR C2 )OR C1 , —C(═NR C2 )N(R C2 ) 2 , —SO 2 R C1 , —S(═O)R C1 , —Si(R C1 ) 3 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, with the proviso that R C  is not —CH 3 ; 
 each instance of R C1  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
 each instance of R C2  is, independently, selected from hydrogen, —OH, —OR C1 , —N(R C3 ) 2 , —CN, —C(═O)R C1 , —C(═O)N(R C3 ) 2 , —CO 2 R C1 , —SO 2 R C1 , —C(═NR C3 )OR C1 , —C(═NR C3 )N(R C3 ) 2 , —SO 2 N(R C3 ) 2 , —SO 2 R C3 , —SO 2 OR C3 , —SOR C1 , —C(═S)N(R C3 ) 2 , —C(═O)SR C3 , —C(═S)SR C3 , —P(═O) 2 R C1 , —P(═O)(R C1 ) 2 , —P(═O) 2 N(R C3 ) 2 , —P(═O)(NR C3 ) 2 , C 2-10  alkyl, C 2-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R C2  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
 or R B  and R C  together with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered ring; 
 wherein: 
 R B  is substituted with the group:
   -L-R D    
 
 wherein: 
 L is a covalent bond or a divalent C 1-10  hydrocarbon chain, wherein one, two or three methylene units of L are optionally and independently replaced with one or more —O—, —S—, —NR B8 —, —(C═NR B8 )—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O) 2 —, divalent carbocyclyl, divalent heterocyclyl, divalent aryl or divalent heteroaryl group; 
 R D  is selected from —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —C(═O)R B7 , —CO 2 H, —CHO, —C(OR B9 ) 2 , —CO 2 R B7 , —OC(═O)R B7 , —OCO 2 R B7 , —C(═O)N(R B8 ) 2 , —OC(═O)N(R B8 ) 2 , —NR B8 C(═O)R B7 , —NR B8 CO 2 R B7 , —NR B8 C(═O)N(R B8 ) 2 , —C(═NR B8 )OR B7 , —OC(═NR B8 )R B7 , —OC(═NR B8 )OR B7 , —C(═NR B8 )N(R B8 ) 2 , —OC(═NR B8 )N(R B8 ) 2 , —NR B8 C(═NR B8 )N(R B8 ) 2 , —C(═O)NR B8 SO 2 R B7 , —NR B8 SO 2 R B7 , —SO 2 N(R B8 ) 2 , —SO 2 R B7 , —SO 2 OR B7 , —OSO 2 R B7 , —S(═O)R B7 , —OS(═O)R B7 , —C(═S)N(R B8 ) 2 , —C(═O)SR B7 , —C(═S)SR B7 , —SC(═S)SR B7 , —P(═O) 2 R B7 , —OP(═O) 2 R B7 , —P(═O)(R B7 ) 2 , —OP(═O)(R B7 ) 2 , —OP(═O)(OR B9 ) 2 , —P(═O) 2 N(R B8 ) 2 , —OP(═O) 2 N(R B8 ) 2 , —P(═O)(NR B8 ) 2 , —OP(═O)(NR B8 ) 2 , —NR B8 P(═O)(OR B9 ) 2 , —NR B8 P(═O)(NR B8 ) 2 , —B(OR B9 ) 2 , —BR B7 (OR B9 ), and tetrazolyl; 
 each instance of R B7  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
 each instance of R B8  is, independently, selected from hydrogen, —OH, —OR B7 , —N(R B9 ) 2 , —CN, —C(═O)R B7 , —C(═O)N(R B9 ) 2 , —CO 2 R B7 , —SO 2 R B7 , —C(═NR B9 )OR B7 , —C(═NR B9 )N(R B9 ) 2 , —SO 2 N(R B9 ) 2 , —SO 2 R B9 , —SO 2 OR B9 , —SOR B7 , —C(═S)N(R B9 ) 2 , —C(═O)SR B9 , —C(═S)SR B9 , —P(═O) 2 R B7 , —P(═O)(R B7 ) 2 , —P(═O) 2 N(R B9 ) 2 , —P(═O)(NR B9 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B8  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; and 
 each instance of R B9  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B9  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. 
 
     
     
         44 . The method of  claim 43 , wherein L is a covalent bond. 
     
     
         45 . The method of  claim 44 , wherein R D  is —CO 2 H. 
     
     
         46 . The method of  claim 43 , wherein R E  is selected from halogen, —OR B10  and —N(R B11 ) 2 . 
     
     
         47 . The method of  claim 43 , wherein R C  is C 3-10  alkyl. 
     
     
         48 . The method of  claim 43 , wherein R C  is C 3-10  carbocyclyl. 
     
     
         49 . The method of  claim 43 , wherein R A  is C 6-14  aryl or 5-14 membered heteroaryl, and R B  is C 6-14  aryl. 
     
     
         50 . The method of  claim 49 , wherein R A  is C 6-14  aryl and R B  is C 6-14  aryl. 
     
     
         51 . The method of  claim 43 , wherein R A  is 5-14 membered heteroaryl and R B  is C 6-14  aryl. 
     
     
         52 . The method of  claim 43 , wherein the compound is of the formula (II): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof; 
         wherein each group W—R 1 , W—R 2 , W—R 3 , W—R 4 , and W—R 5  independently represents either a nitrogen atom (N) or C—R 1 , C—R 2 , C—R 3 , C—R 4 , or C—R 5 , respectively; and 
         wherein R 1 , R 2 , R 3 , R 4  and R 5  are, independently, selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —OH, —OR A1 , —ON(R A2 ) 2 , —N(R A2 ) 2 , —N(OR A3 )R A3 , —SH, —SR A1 , —SSR A3 , —C(═O)R A1 , —CO 2 H, —CHO, —C(OR A3 ) 2 , —CO 2 R A1 , —OC(═O)R A1 , —OCO 2 R A1, —C(═O)N(R A2 ) 2 , —OC(═O)N(R A2 ) 2 , —NR A2 C(═O)R A1 , —NR A2 C 2 R A1 , —NR A2 C(═O)N(R A2 ) 2 , —C(═NR A2 )OR A1 , —OC(═NR)R A1 , —OC(═NR A2 )OR A1 , —C(═NR A2 )N(R A2 ) 2 , —OC(═NR A2 )N(R A2 ) 2 , —NR A2 C(═NR A2 )N(R A2 ) 2 , —C(═O)NR A2 SO 2 R A1 , —NR A2 SO 2 R A1 , —SO 2 N(R A2 ) 2 , —SO 2 R A1 , —SO 2 OR A1 , —OSO 2 R A1 , —S(═O)R A1 , —OS(═O)R A1 , —Si(R A1 ) 3 , —OSi(R A1 ) 3 —C(═S)N(R A2 ) 2 , —C(═O)SR A1 , —C(═S)SR A1 , —SC(═S)SR A1 , —P(═O) 2 R A1 , —OP(═O) 2 R A1 , —P(═O)(R A1 ) 2 , —OP(═O)(R A1 ) 2 , —OP(═O)(OR A3 ) 2 , —P(═O) 2 N(R A2 ) 2 , —OP(═O) 2 N(R A2 ) 2 , —P(═O)(NR A2 ) 2 , —OP(═O)(NR A3 ) 2 , —NR A2 P(═O)(OR A3 ) 2 , —NR A2 P(═O)(NR A2 ) 2 , —P(R A3 ) 2 , —P(R A3 ) 3 , —OP(R A3 ) 2 , —OP(R A3 ) 3 , —B(OR A3 ) 2 , or —BR A1 (OR A3 ), C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; or one or more of R 1  and R 2 , R 2  and R 3 , R 3  and R 4  or R 4  and R 5  are joined to form a C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl or 5-14 membered heteroaryl ring; 
         each instance of R A1  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
         each instance of R A2  is, independently, selected from hydrogen, —OH, —OR A1 , —N(R A3 ) 2 , —CN, —C(═O)R A1 , —C(═O)N(R A3 ) 2 , —CO 2 R A1 , —SO 2 R A1 , —C(═NR A3 )OR A1 , —C(═NR A3 )N(R A3 ) 2 , —SO 2 N(R A3 ) 2 , —SO 2 R A3 , —SO 2 OR A3 , —SOR A1 , —C(═S)N(R A3 ) 2 , —C(═O)SR A3 , —C(═S)SR A3 , —P(═O) 2 R A1 , —P(═O)(R A1 ) 2 , —P(═O) 2 N(R A3 ) 2 , —P(═O)(NR A3 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2 -10 alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R A2  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; and 
         each instance of R A3  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3 -10 carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R A3  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         wherein each group W—R 6 , W—R 7 , W—R 8 , W—R 9 , and W—R 10  independently represents either a nitrogen atom (N) or C—R 6 , C—R 7 , C—R 8 , C—R 9 , or C—R 10 , respectively; 
         R 6 , R 7 , R 8 , R 9  and R 10  are, independently, selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —OH, —OR B1 , —ON(R B2 ) 2 , —N(R B2 ) 2 , —N(OR B3 )R B3 , —SH, —SR B1 , —SSR B3 , —C(═O)R B1 , —CO 2 H, —CHO, —C(OR B3 ) 2 , —CO 2 R B1 , —OC(═O)R B1 , —OCO 2 R B1 , —C(═O)N(R B2 ) 2 , —OC(═O)N(R B2 ) 2 , —NR B2 C(═O)R B1 , —NR B2 CO 2 R B1 , —NR B2 C(═O)N(R B2 ) 2 , —C(═NR B2 )OR B1 , —OC(═NR B2 )R B1 , —OC(═NR B2 )OR B1 , —C(═NR B2 )N(R B2 ) 2 , —OC(═NR B2 )N(R B22 , —NR B2 C(═NR B2 )N(R B2 ) 2 , —C(═O)NR B2 SO 2 R B1 , —NR B2 SO 2 R B1 , —SO 2 N(R B2 ) 2 , —SO 2 R B1 , —SO 2 OR B1 , —OSO 2 R B1 , —S(═O)R B1 , —OS(═O)R B1 , —Si(R B1 ) 3 , —OSi(R B1 ) 3 —C(═S)N(R B2 ) 2 , —C(═O)SR B1 , —C(═S)SR B1 , —SC(S)SR B1 , —P(═O) 2 R B1 , —OP(═O) 2 R B1 , —P(═O)(R B1 ) 2 , —OP(═O)(R B1 ) 2 , —OP(═O)(OR B3 ) 2 , —P(═O) 2 N(R B2 ) 2 , —OP(═O) 2 N(R B2 ) 2 , —P(═O)(NR B2 ) 2 , —OP(═O)(NR B2 ) 2 , —NR B2 P(═O)(OR B3 ) 2 , —R B2 P(═O)(NR B2 ) 2 , —P(R B3 ) 2 , —P(R B3 ) 3 , —OP(R B3 ) 2 , —OP(R B3 ) 3 , —B(OR B3 ) 2 , —BR B1 (OR B3 ), C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, 5-14 membered heteroaryl, -L-R D  and —R E ; or one or more of R 6  and R 7 , R 7  and R 8 , R 8  and R 9  or R 9  and R 10  are joined to form a C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl or 5-14 membered heteroaryl ring; or R 10  and R C  are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         wherein at least one of R 6 , R 7 , R 8 , R 9 , and R 10  is the group -L-R D ; 
         each instance of R B1  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
         each instance of R B2  is, independently, selected from hydrogen, —OH, —OR B1 , —N(R B3 ) 2 , —CN, —C(═O)R B1 , —C(═O)N(R B3 ) 2 , —CO 2 R B1 , —SO 2 R B1 , —C(═NR B3 )OR B1 , —C(═NR B3 )N(R B3 ) 2 , —SO 2 N(R B3 ) 2 , —SO 2 R B3 , —SO 2 OR B3 , —SOR B1 , —C(═S)N(R B3 ) 2 , —C(═O)SR B3 , —C(═S)SR B3 , —P(═O) 2 R B1 , —P(═O)(R B1 ) 2 , —P(═O) 2 N(R B3 ) 2 , —P(═O)(NR B3 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B2  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         each instance of R B3  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B3  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         L is a covalent bond or a divalent C 1-10  hydrocarbon chain, wherein one, two or three methylene units of L are optionally and independently replaced with one or more —O—, —S—, —NR B8 —, —(C═NR B8 )—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O) 2 —, divalent carbocyclyl, divalent heterocyclyl, divalent aryl or divalent heteroaryl group; and 
         wherein R D  is selected from —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —C(═O)R B7 , —CO 2 H, —CHO, —C(OR B9 ) 2 , —CO 2 R B7 , —OC(═O)R B7 , —OCO 2 R B7 , —C(═O)N(R B8 ) 2 , —OC(═O)N(R B8 ) 2 , —NR B8 C(═O)R B7 , —NR B8 CO 2 R B7 , —NR B8 C(═O)N(R B8 ) 2 , —C(═NR B8 )OR B7 , —OC(═NR B8 )R B7 , —OC(═NR B8 )OR B7 , —C(═NR B8 )N(R B8 ) 2 , —OC(═NR B8 )N(R B8 ) 2 , —NR B8 C(═NR B8 )N(R B8 ) 2 , —C(═O)NR B8 SO 2 R B7 , —NR B8 SO 2 R B7 , —SO 2 N(R B8 ) 2 , —SO 2 R B7 , —SO 2 OR B7 , —OSO 2 R B7 , —S(═O)R B7 , —OS(═O)R B7 , —C(═S)N(R B8 ) 2 , —C(═O)SR B7 , —C(═S)SR B7 , —SC(═S)SR B7 , —P(═O) 2 R B7 , —OP(═O) 2 R B7 , —P(═O)(R B7 ) 2 , —OP(═O)(R B7 ) 2 , —OP(═O)(OR B9 ) 2 , —P(═O) 2 N(R B8 ) 2 , —OP(═O) 2 N(R B8 ) 2 , —P(═O)(NR B8 ) 2 , —OP(═O)(NR B8 ) 2 , —NR B8 P(═O)(OR B9 ) 2 , —NR B8 P(═O)(NR B8 ) 2 , —B(OR B9 ) 2 , —BR B7 (OR B9 ) and tetrazolyl; 
         each instance of R B7  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
         each instance of R B8  is, independently, selected from hydrogen, —OH, —OR B7 , —N(R B9 ) 2 , —CN, —C(═O)R B7 , —C(═O)N(R B9 ) 2 , —CO 2 R B7 , —SO 2 R B7 , —C(═NR B9 )OR B7 , —C(═NR B9 )N(R B9 ) 2 , —SO 2 N(R B9 ) 2 , —SO 2 R B9 , —SO 2 OR B9 , —SOR B7 , —C(═S)N(R B9 ) 2 , —C(═O)SR B9 , —C(═S)SR B9 , —P(═O) 2 R B7 , —P(═O)(R B7 ) 2 , —P(═O) 2 N(R B9 ) 2 , —P(═O)(NR B9 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B8  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; and 
         each instance of R B9  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B9  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         R E  is selected from halogen, —OH, —OR B10 , —ON(R B11 ) 2 , —N(R B11 ) 2 , —N(OR B12 )R B12 , —SH, —SR B10 , —SSR B12 , —OC(═O)R B10 , —OCO 2 R B10 , —OC(═O)N(R B1 ) 2 , —NR B11 C(═O)R B10 , —NR B11 CO 2 R B10 , —NR B11 C(═O)N(R B11 ) 2 , —OC(═NR B11 )R B11 , —OC(═NR B11 )OR B10 , —OC(═NR B11 )N(R B11 ) 2 , —R B11 C(═NR B11 )N(R B11 ) 2 , —R B11 SO 2 R B10 , —OSO 2 R B10 , —OS(═O)R B10 , —Si(R B10 ) 3 , —OSi(R B10 ) 3 , —SC(S)SR B10 , —OP(═O) 2 R B10 , —OP(═O)(R B10 ) 2 , —OP(═O)(OR B12 ) 2 , —OP(═O) 2 N(R B11 ) 2 , —OP(═O)(NR B11 ) 2 , —NR B11 P(═O)(OR B12 ) 2 , —NR B11 P(═O)(NR B11 ) 2 , —P(R B12 ) 2 , —P(R B12 ) 3 , —OP(R B12 ) 2 , —OP(R B12 ) 3 , 3-14 membered heterocyclyl and 5-14 membered heteroaryl, wherein the point of attachment of the 3-14 membered heterocyclyl or 5-14 membered heteroaryl group is on a nitrogen atom; 
         each instance of R B10  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
         each instance of R B11  is, independently, selected from hydrogen, —OH, —OR B10 , —N(R B12 ) 2 , —CN, —C(═O)R B10 , —C(═O)N(R B12 ) 2 , —CO 2 R B10 , —SO 2 R B10 , —C(═NR B12 )OR B10 , —C(═NR B12 )N(R B12 ) 2 , —SO 2 N(R B12 ) 2 , —SO 2 R B12 , —SO 2 OR B12 , —SOR B10 , —C(═S)N(R B12 ) 2 , —C(═O)SR B12 , —C(═S)SR B12 , —P(═O) 2 R B10 , —P(═O)(R B10 ) 2 , —P(═O) 2 N(R B12 ) 2 , —P(═O)(NR B12 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B11  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         each instance of R B12  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B12  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         R C  is selected from —OH, —OR C1 , —ON(R C2 ) 2 , —N(R C2 ) 2 , —C(═O)R C1 , —CHO, —CO 2 R C1 , —C(═O)N(R C2 ) 2 , —C(═NR C2 )OR C1 , —C(═NR C2 )N(R C2 ) 2 , —SO 2 R C1 , —S(═O)R C1 , —Si(R C1 ) 3 , C 1-10 alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, with the proviso that R C  is not —CH 3 ; 
         each instance of R C1  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; and 
         each instance of R C2  is, independently, selected from hydrogen, —OH, —OR C1 , —N(R C3 ) 2 , —CN, —C(═O)R Cl , —C(═O)N(R C3 ) 2 , —CO 2 R C1 , —SO 2 R C1 , —C(═NR C3 )OR C1 , —C(═NR C3 )N(R C3 ) 2 , —SO 2 N(R C3 ) 2 , —SO 2 R C3 , —SO 2 OR C3 , —SOR C1 , —C(═S)N(R C3 ) 2 , —C(═O)SR C3 , —C(═S)SR C3 , —P(═O) 2 R C1 , —P(═O)(R C1 ) 2 , —P(═O) 2 N(R C3 ) 2 , —P(═O)(NR C3 ) 2 , C 2-10  alkyl, C 2-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R C2  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. 
       
     
     
         53 . The method of  claim 52 , wherein at least one of R 6 , R 7 , R 8 , R 9  and R 10  is the group —R E . 
     
     
         54 . The method of  claim 42 , wherein the FASN inhibitor is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof. 
       
     
     
         55 . The method of  claim 42 , which further comprises administration of one or more anti-cancer agents. 
     
     
         56 . The method of  claim 55 , wherein the anti-cancer agent is selected from an interferon, an antibody, an anti-estrogen, an LHRH agonist, an anti-androgen, a photodynamic therapy, phthalocyanine, photosensitizer Pc4, demethoxy-hypocrellin A, a nitrogen mustard, a nitrosourea, an alkylsulphonate, a triazene, a platinum containing compound, a vinca alkaloid, a taxoid, an epipodophyllin, an anti-metabolite, a DHFR inhibitor, an IMP dehydrogenase inhibitor, a ribonuclotide reductase inhibitor, a uracil analog, a cytosine analog, a purine analog, a vitamin D3 analog, an isoprenylation inhibitor, a dopaminergic neurotoxin, a cell cycle inhibitor, actinomycin, bleomycin, anthracycline, MDR inhibitor, Ca2+ ATPase inhibitor, and a tyrosine kinase inhibitor. 
     
     
         57 . A method of inhibiting fatty acid synthase in a subject having prostate cancer, where in the method comprises administering to the subject a therapeutically effective amount of a fatty acid synthase inhibitor. 
     
     
         58 . The method of  claim 57 , wherein the FASN inhibitor is a compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof; 
       
       wherein:
 R A  is selected from C 6-14  aryl and 5-14 membered heteroaryl; 
 R B  is selected from C 6-14  aryl and 5-14 membered heteroaryl; 
 R C  is selected from —OH, —OR C1 , —ON(R C2 ) 2 , —N(R C2 ) 2 , —C(═O)R C1 , —CHO, —CO 2 R C1 , —C(═O)N(R C2 ) 2 , —C(═NR C2 )OR C1 , —C(═NR C2 )N(R C2 ) 2 , —SO 2 R C1 , —S(═O)R C1 , —Si(R C1 ) 3 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, with the proviso that R C  is not —CH 3 ; 
 each instance of R C1  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
 each instance of R C2  is, independently, selected from hydrogen, —OH, —OR C1 , —N(R C3 ) 2 , —CN, —C(═O)R C1 , —C(═O)N(R C3 ) 2 , —CO 2 R C1 , —SO 2 R C1 , —C(═NR C3 )OR C1 , —C(═NR C3 )N(R C3 ) 2 , —SO 2 N(R C3 ) 2 , —SO 2 R C3 , —SO 2 OR C3 , —SOR C1 , —C(═S)N(R C3 ) 2 , —C(═O)SR C3 , —C(═S)SR C3 , —P(═O) 2 R C1 , —P(═O)(R C1 ) 2 , —P(═O) 2 N(R C3 ) 2 , —P(═O)(NR C3 ) 2 , C 2-10  alkyl, C 2-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R C2  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
 or R B  and R C  together with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered ring; 
 wherein: 
 R B  is substituted with the group:
   -L-R D    
 
 wherein: 
 L is a covalent bond or a divalent C 1-10  hydrocarbon chain, wherein one, two or three methylene units of L are optionally and independently replaced with one or more —O—, —S—, —NR B8 —, —(C═NR B8 )—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O) 2 —, divalent carbocyclyl, divalent heterocyclyl, divalent aryl or divalent heteroaryl group; 
 R D  is selected from —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —C(═O)R B7 , —CO 2 H, —CHO, —C(OR B9 ) 2 , —CO 2 R B7 , —OC(═O)R B7 , —OCO 2 R B7 , —C(═O)N(R B8 ) 2 , —OC(═O)N(R B8 ) 2 , —NR B8 C(═O)R B7 , —NR B8 CO 2 R B7 , —NR B8 C(═O)N(R B8 ) 2 , —C(═NR B8 )OR B7 , —OC(═NR B8 )R B7 , —OC(═NR B8 )OR B7 , —C(═NR B8 )N(R B8 ) 2 , —OC(═NR B8 )N(R B8 ) 2 , —NR B8 C(═NR B8 )N(R B8 ) 2 , —C(═O)NR B8 SO 2 R B7 , —NR B8 SO 2 R B7 , —SO 2 N(R B8 ) 2 , —SO 2 R B7 , —SO 2 OR B7 , —OSO 2 R B7 , —S(═O)R B7 , —OS(═O)R B7 , —C(═S)N(R B8 ) 2 , —C(═O)SR B7 , —C(═S)SR B7 , —SC(═S)SR B7 , —P(═O) 2 R B7 , —OP(═O) 2 R B7 , —P(═O)(R B7 ) 2 , —OP(═O)(R B7 ) 2 , —OP(═O)(OR B9 ) 2 , —P(═O) 2 N(R B8 ) 2 , —OP(═O) 2 N(R B8 ) 2 , —P(═O)(NR B8 ) 2 , —OP(═O)(NR B8 ) 2 , —NR B8 P(═O)(OR B9 ) 2 , —NR B8 P(═O)(NR B8 ) 2 , —B(OR B9 ) 2 , —BR B7 (OR B9 ), and tetrazolyl; 
 each instance of R B7  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
 each instance of R B8  is, independently, selected from hydrogen, —OH, —OR B7 , —N(R B9 ) 2 , —CN, —C(═O)R B7 , —C(═O)N(R B9 ) 2 , —CO 2 R B7 , —SO 2 R B7 , —C(═NR B9 )OR B7 , —C(═NR B9 )N(R B9 ) 2 , —SO 2 N(R B9 ) 2 , —SO 2 R B9 , —SO 2 OR B9 , —SOR B7 , —C(═S)N(R B9 ) 2 , —C(═O)SR B9 , —C(═S)SR B9 , —P(═O) 2 R B7 , —P(═O)(R B7 ) 2 , —P(═O) 2 N(R B9 ) 2 , —P(═O)(NR B9 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B8  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; and 
 each instance of R B9  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl, or two R B9  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. 
 
     
     
         59 . The method of  claim 57 , wherein the FASN inhibitor is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof. 
       
     
     
         60 . The method of  claim 57 , which further comprises administration of one or more anti-cancer agents. 
     
     
         61 . The method of  claim 60 , wherein the anti-cancer agent is selected from an interferon, an antibody, an anti-estrogen, an LHRH agonist, an anti-androgen, a photodynamic therapy, phthalocyanine, photosensitizer Pc4, demethoxy-hypocrellin A, a nitrogen mustard, a nitrosourea, an alkylsulphonate, a triazene, a platinum containing compound, a vinca alkaloid, a taxoid, an epipodophyllin, an anti-metabolite, a DHFR inhibitor, an IMP dehydrogenase inhibitor, a ribonuclotide reductase inhibitor, a uracil analog, a cytosine analog, a purine analog, a vitamin D3 analog, an isoprenylation inhibitor, a dopaminergic neurotoxin, a cell cycle inhibitor, actinomycin, bleomycin, anthracycline, MDR inhibitor, Ca2+ ATPase inhibitor, and a tyrosine kinase inhibitor. 
     
     
         62 . A method of treating a cancer comprising administering to a subject a therapeutically effective amount of 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof. 
       
     
     
         63 . The method of  claim 62 , wherein the cancer is selected from bladder cancer, brain cancer, breast cancer, colorectal cancer, esophageal cancer, endometrial cancer, gastric cancer, gastrointestinal stromal tumor, kidney cancer, liver cancer, lung cancer, mesothelioma, multiple myeloma, neuroblastoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, Paget's disease of the vulva, retinoblastoma, soft tissue sarcoma, skin cancer or thyroid cancer. 
     
     
         64 . The method of  claim 62 , wherein the cancer is prostate cancer. 
     
     
         65 . The method of  claim 62 , wherein the cancer is liver cancer. 
     
     
         66 . The method of  claim 62 , wherein the cancer is colorectal cancer. 
     
     
         67 . The method of  claim 62 , wherein the cancer is breast cancer. 
     
     
         68 . The method of  claim 62 , wherein the cancer is ovarian cancer. 
     
     
         69 . The method of  claim 62 , wherein the cancer is hepatocellular carcinoma. 
     
     
         70 . The method of  claim 62 , which further comprises administration of one or more anti-cancer agents. 
     
     
         71 . The method of  claim 70 , wherein the anti-cancer agent is selected from an interferon, an antibody, an anti-estrogen, an LHRH agonist, an anti-androgen, a photodynamic therapy, phthalocyanine, photosensitizer Pc4, demethoxy-hypocrellin A, a nitrogen mustard, a nitrosourea, an alkylsulphonate, a triazene, a platinum containing compound, a vinca alkaloid, a taxoid, an epipodophyllin, an anti-metabolite, a DHFR inhibitor, an IMP dehydrogenase inhibitor, a ribonuclotide reductase inhibitor, a uracil analog, a cytosine analog, a purine analog, a vitamin D3 analog, an isoprenylation inhibitor, a dopaminergic neurotoxin, a cell cycle inhibitor, actinomycin, bleomycin, anthracycline, MDR inhibitor, Ca2+ ATPase inhibitor, and a tyrosine kinase inhibitor. 
     
     
         72 . A method of treating an obesity related disorder comprising administering to a subject a therapeutically effective amount of 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof. 
       
     
     
         73 . The method of  claim 72 , wherein the obesity related disorder is selected from Type II diabetes mellitus, elevated blood pressure, elevated cholesterol levels, ischemic heart disease, arterial vascular disease, angina, myocardial infarction, stroke, migraines, congestive heart failure, deep vein thrombosis, pulmonary embolism, gall stones, gastroesophagael reflux disease, obstructive sleep apnea, obesity hypoventilation syndrome, asthma, gout, poor mobility, back pain, erectile dysfunction, urinary incontinence, liver injury, fatty liver, and chronic renal failure.