Triazoles as inhibitors of fatty acid synthase

Abstract

Provided herein are triazole FASN inhibitors of the formula (I): or a pharmaceutically acceptable form thereof; wherein the variables R A , X, 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 . A method of treating a FASN-mediated disorder selected from hyperproliferative disorders, inflammatory disorders, obesity related disorders, Type II diabetes mellitus, fatty liver disease, microbial infections, viral infections, bacterial infections, fungal infections, parasitic infections, and protozoal infections comprising administering to a subject a therapeutically effective amount of a compound of the formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof; 
         wherein: 
         R A  is selected C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, 5-14 membered heteroaryl, and hydrogen; 
         X is selected from hydrogen, —CN, —CHO, —C(═O)R X1 , —C(═O)N(R X2 ) 2 , —CO 2 H, CO 2 R X1 , —SO 2 R X1 , —C(═NR X2 )OR X1 , —C(═NR X2 )N(R X2 ) 2 , —SO 2 N(R X2 ) 2 , —SO 2 R X1 , —SO 3 H, —SO 2 OR X1 , —SOR X1 , —C(═S)N(R X2 ) 2 , —C(═O)SR X1 , —C(═S)SR X1 , —P(═O) 2 R X1 , —P(═O)(R X1 ) 2 , —P(═O) 2 N(R X2 ) 2 , —P(═O)(NR X2 ) 2 , C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; or 
         R A  and X, together with the carbon atoms to which each is attached, are joined to form a 5-10 membered carbocyclyl, heterocyclyl, aryl or heteroaryl ring; 
         R B  is selected from C 6-14  aryl, 5-14 membered heteroaryl, C 1-10 alkyl, C 2-10  alkenyl, C 2-10  alkynyl, 3-14 membered heteroaliphatic, C 3-10  carbocyclyl, and 3-14 membered heterocyclyl; 
         R C  is selected from hydrogen, —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; 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 carbocyclyl, heterocyclyl, aryl or heteroaryl ring; 
         each R C1  and R X1  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 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 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 R X2  is, independently, selected from hydrogen, —OH, —N(R X3 ) 2 , —CN, —C(═O)R X1 , —C(═O)N(R X3 ) 2 , —CO 2 R X1 , —SO 2 R X1 , —C(═NR X3 )OR X1 , —C(═NR X3 )N(R X3 ) 2 , —SO 2 N(R X3 ) 2 , —SO 2 R X3 , —SO 2 OR X3 , —SOR X1 , —C(═S)N(R X3 ) 2 , —C(═O)SR X3 , —C(═S)SR X3 , —P(═O) 2 R X1 , —P(═O)(R X1 ) 2 , —P(═O) 2 N(R X3 ) 2 , —P(═O)(NR X3 ) 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; and 
         each R C3  and R X3  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. 
       
     
     
         2 . The method of  claim 1 , wherein X is selected from hydrogen, —CN, —CHO, —C(═O)R C1 , —C(═O)N(R C2 ) 2 , —CO 2 H, —CO 2 R C1 , —C(═NR C2 )OR C1 , —C(═NR C2 )N(R C2 ) 2 , —C(═S)N(R C2 ) 2 , —C(═O)SR C1 , —C(═S)SR C1 , C 1-10  perhaloalkyl, C 6-14  aryl, and 5-14 membered heteroaryl. 
     
     
         3 . The method of  claim 2 , wherein X is —CN. 
     
     
         4 . The method of  claim 1 , wherein R A  is selected from C 6-14  aryl and 5-14 membered heteroaryl. 
     
     
         5 . The method of  claim 4 , wherein R A  is C 6-14  aryl. 
     
     
         6 . The method of  claim 5 , wherein R A  is a group of the formula (ii): 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4  and R 5  are independently selected from hydrogen, halogen, —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —OH, —OR A1 , —ON(R A2 ) 2 , —N(R) 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 CO 2 R A1 , NR A2 C(═O)N(R A2 ) 2 , —C(═NR A2 )OR A1 , —OC(═NR A2 )R A1 , —OC(═NR A2 )OR A1 , —C(═NR A2 )N(R A2 ) 2 , —OC(═NR A2 )N(R) 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 A2 ) 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 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 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 R A3  is, independently, selected from hydrogen, C 1-10  alkyl, C 1-10  perhaloalkyl, 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. 
       
     
     
         7 . The method of  claim 6 , wherein each of R 1 R 2 , R 3 , R 4  and R 5  is independently selected from hydrogen, halogen, —CN, —OR A1 , —N(R A2 ) 2 , —CO 2 H, —CO 2 R A1 , —C(═O)N(R A2 ) 2 , —SO 2 R A1 , C 1-10  alkyl, C 2-10  alkynyl, 3-14 membered heterocyclyl, and C 6-14  aryl; 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 5-14 membered heteroaryl ring. 
     
     
         8 . The method of  claim 7 , wherein each of R 1 , R 2 , R 3 , R 4  and R 5  is independently selected from hydrogen, halogen, —OR A1 , C 1-10  alkyl, and —C(═O)N(R A2 ) 2 ; or R 4  and R 5  are joined to form a 5-14 membered heteroaryl ring. 
     
     
         9 . The method of  claim 6 , wherein R A  is a group of the formula (ii-d): 
       
         
           
           
               
               
           
         
         wherein one of R 1  and R 5  is selected from halogen, —CN, —OR A1 , —N(R A2 ) 2 , —CO 2 H, —CO 2 R A1 , —C(═O)N(R A2 ) 2 , —SO 2 R A1 , C 1-10  alkyl. C 2-10  alkynyl, 3-14 membered heterocyclyl, and C 6-14  aryl, and the other of R 1  and R 3  is selected from halogen, —CN, —OR A1 , —N(R A2 ) 2 , —CO 2 H, —CO 2 R A1 , —C(═O)N(R A2 ) 2 , —SO 2 R A1 , C 1-10  alkyl, C 2-10  alkynyl, 3-14 membered heterocyclyl, and C 6-14  aryl. 
       
     
     
         10 . The method of  claim 9 , wherein each of R 1  and R 5  is independently halogen. 
     
     
         11 . The method of  claim 10 , wherein each of R 1  and R 5  is independently selected from fluoro and chloro. 
     
     
         12 . The method of  claim 1 , wherein R B  and R C  together with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered carbocyclyl, heterocyclyl, aryl or heteroaryl ring. 
     
     
         13 . The method of  claim 12 , wherein 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 of the formula (xiv): 
       
         
           
           
               
               
           
         
         wherein: 
         Q is N, NR 40 , O, S, or CR 41 R 42 ; 
         m is 0, 1 or 2; and 
         each R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49  and R 50  is, independently, selected from hydrogen, halogen, —CN, —NO 2 , —N 3 , —SO 2 H, —SO 3 H, —OH, —OR F1 , —ON(R F2 ) 2 , —N(R F2 ) 2 , —N(OR F3 )R F3 , —SH, —SR F1 , —SSR F3 , —C(═O)R F1 , —CO 2 H, —CHO, —C(OR F3 ) 2 , —CO 2 R F1 , OC(═O)R F1 , —OCO 2 R F1 , C(═O)N(R F2 ) 2 , —OC(═O)N(R F2 ) 2 , —NR F2 , —NR F2 C(═O)R F1 , —NR F2 C(═O)N(R F2 ) 2 , —C(═NR F2 )OR F1 , —OC(═NR F2 )R F1 , —OC(═NR F2 )OR F1 , —C(═NR F2 )N(R F2 ) 2 , —OC(═NR F2 )N(R F2 ) 2 , —NR F2 C(═NR F2 N(R F2 ) 2 , —C(═O)NR F2 SO 2 R BC1 , —NR F2 SO 2 R F1 , —SO 2 N(R F2 ) 2 , —SO 2 R F1 , —SO 2 OR F1 , —OSO 2 R F1 , —S(═O)R F1 , —OS(═O)R F1 , —Si(R F1 ) 3 , —OSi(R F1 ) 3 , —C(═S)N(R F2 ) 2 , —C(═O)SR F1 , —C(═S)SR F1 , —SC(═S)SR F1 , —P(═O) 2 R F1 , —OP(═O) 2 R F1 , —P(═O)(R F1 ) 2 , —OP(═O)(R F1 ) 2 , —OP(═O)(OR F3 ) 2 , —P(═O) 2 N(R F2 ) 2 , —OP(═O) 2 N(R F2 ) 2 , —P(═O)(NR F2 ) 2 , —OP(═O)(NR F2 ) 2 , —NR F2 P(═O)(OR F3 ) 2 , —NR F2 (═O)(NR F2 ) 2 , —P(R F3 ) 2 , —P(R F3 ) 3 , —OP(R F3 ) 2 , —OP(R F3 ) 3 , —B(OR F3 ) 2 , or —BR F1 (OR F3 ), 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 47  and R 49 , R 48  and R 50 , R 49  and R 41 , R 50  and R 42 , R 41  and R 45 , R 42  and R 46 , R 45  and R 43 , and R 46  and R 44  are joined to form a double bond or a C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl or 5-14 membered heteroaryl ring; optionally wherein Q is N, then N and R 49  or N and R 46  are joined to form a double bond; 
         R 40  is selected from hydrogen, —OH, —OR F1 , —N(R F3 ) 2 , —CN, —C(═O)R F1 , —C(═O)N(R F3 ) 2 , —CO 2 R F1 , —SO 2 R F1 , —C(═NR F3 )OR F1 , —C(═NR F3 )N(R F3 ) 2 , —SO 2 N(R F3 ) 2 , —SO 2 R F3 , —SO 2 OR F3 , —SOR F1 , —C(═S)N(R F3 ) 2 , —C(═O)SR F3 , —C(═S)SR F3 , —P(═O) 2 R F1 , —P(═O)(R F1 ) 2 , —P(═O) 2 N(R F3 ) 2 , —P(═O)(NR F3 ) 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 R 49  and R 40  or R 40  and R 45  are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; 
         each R F1  is, independently, selected from C 1-10  alkyl, C 1-10  perhaloalkyl, C 2-10  alkenyl, C 2-10  alkynyl, C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl, and 5-14 membered heteroaryl; 
         each R F2  is, independently, selected from hydrogen, —OH, —OR F1 , —N(R F3 ) 2 , —CN, —C(═O)R F1 , —C(═O)N(R F3 ) 2 , —CO 2 R F1 , —SO 2 R F1 , —C(═NR F3 )OR F1 , —C(═NR F3 )N(R F3 ) 2 , —SO 2 N(R F3 ) 2 , —SO 2 R F3 , —SO 2 OR F3 , —S(═O)R F1 , —C(═S)N(R F3 ) 2 , —C(═O)SR F3 , —C(═S)SR F3 , —P(═O) 2 R F1 , —P(═O)(R F1 ) 2 , —P(═O) 2 N(R F3 ) 2 , —P(═O)(NR F3 ) 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 F2  groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; and 
         each R F3  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 F3  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 C 3-10  carbocyclyl, divalent 3-14 membered heterocyclyl, divalent C 6-14  aryl or divalent 5-14 membered 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 , and —BR B7 (OR B9 ); 
         each 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 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 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 B11 ) 2 , —NR B11 C(═O)R B19 , —NR B11 CO 2 R B10 , NR B10 , —NR B11 C(═O)N(R B11 ) 2 , —OC(═NR B11 )R 10 , —OC(═NR B11 OR B10 , —OC(═NR B11 )N(R B11 ) 2 , —NR B11 C(═NR B11 )N(R B11 ) 2 , —NR 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 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 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; and 
         each 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. 
       
     
     
         14 . The method of  claim 13 , wherein R 47  and R 49  are joined to form a C 3-10  carbocyclyl, 3-14 membered heterocyclyl, C 6-14  aryl or 5-14 membered heteroaryl ring. 
     
     
         15 . The method of  claim 14 , wherein R 47  and R 49  are joined to form a C 3-10  carbocyclyl. 
     
     
         16 . The method of  claim 15 , wherein Q is CR 41 R 42 . 
     
     
         17 . The method of  claim 16 , wherein m is 1. 
     
     
         18 . The method of  claim 17 , wherein each R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 48 , and R 50  is hydrogen; and R 47  and R 49  are joined to form a C 3-10  carbocyclyl. 
     
     
         19 . The method of  claim 18 , wherein R B  and R C  together with the nitrogen (N) atom to which each is attached are joined to form a group of the formula (xiv-a): 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 1 , wherein R B  is C 6-14  aryl or 5-14 membered heteroaryl. 
     
     
         21 . The method of  claim 20 , wherein R B  is C 6-14  aryl. 
     
     
         22 . The method of  claim 21 , wherein R B  is phenyl. 
     
     
         23 . The method of  claim 22 , wherein R B  is unsubstituted phenyl. 
     
     
         24 . The method of  claim 22 , wherein R B  is phenyl that is substituted with 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)—, —S(═O)—. —S(═O) 2 —, divalent C 3-10  carbocyclyl, divalent 3-14 membered heterocyclyl, divalent C 6-14  aryl or divalent 5-14 membered heteroaryl group; and   R D  is selected from —C(═O)R B7 , —CO 2 H, —CHO, and —CO 2 R B7 ;   wherein R B7  is 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.   
     
     
         25 . The method of  claim 24 , wherein L is a covalent bond, and R D  is —CO 2 H. 
     
     
         26 . The method of  claim 1 , wherein R C  is an acyclic group. 
     
     
         27 . The method of  claim 26 , wherein R C  is C 1-10  alkyl. 
     
     
         28 . The method of  claim 27 , wherein R C  is unsubstituted C 1-10  alkyl. 
     
     
         29 . The method of  claim 28 , wherein R C  is unsubstituted ethyl or unsubstituted isopropyl. 
     
     
         30 . The method of  claim 1 , wherein R B  is C 6-14  aryl or 5-14 membered heteroaryl; and R C  is C 1-10  alkyl. 
     
     
         31 . The method of  claim 30 , wherein R B  is C 6-14  aryl; and R C  is C 1-10  alkyl. 
     
     
         32 . The method of  claim 1 , wherein:
 R A  is C 6-14  aryl;   R B  and R C  together with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered carbocyclyl, heterocyclyl, aryl or heteroaryl ring; and   X is selected from hydrogen, —CN, —CHO, —C(═O)R C1 , —C(═O)N(R C2 ) 2 , —CO 2 H, —CO 2 R C1 , —C(═NR C2 )OR C1 , —C(NR C2 N(R C2 ) 2 , —C(═S)N(R C2 ) 2 , —C(═O)SR C1 —C(═S)SR C1 , C 1-10  perhaloalkyl, C 6-14  aryl, and 5-14 membered heteroaryl.   
     
     
         33 . The method of  claim 32 , wherein X is —CN. 
     
     
         34 . The method of  claim 1 , wherein:
 R A  is C 6-14  aryl;   R B  is C 6-14  aryl or 5-14 membered heteroaryl;   R C  is an acyclic group; and   X is selected from hydrogen, —CN, —CHO, —C(═O)R C1 , —C(═O)N(R C2 ) 2 , —CO 2 H, —CO 2 R C1 , —C(═NR C2 )OR C1 , —C(═NR C2 )N(R C2 ) 2 , —C(═S)N(R C2 ) 2 , —C(═O)SR C1 , —C(═S)SR C1 , C 1-10  perhaloalkyl, C 6-14  aryl, and 5-14 membered heteroaryl.   
     
     
         35 . The method of  claim 34 , wherein R B  is C 6-14  aryl and R C  is C 1-10  alkyl. 
     
     
         36 . The method according to  claim 34 , wherein X is —CN. 
     
     
         37 - 38 . (canceled) 
     
     
         39 . The method of  claim 1 , wherein the FASN-mediated disorder is a microbial infection. 
     
     
         40 . The method of  claim 39 , wherein the microbial infection is a viral infection. 
     
     
         41 . The method of  claim 40 , wherein the viral infection is an infection with an enveloped virus or a picornavirus. 
     
     
         42 . The method of  claim 40 , wherein the viral infection is selected from HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-8, HMCV, CVB3, influenza type A, influenza type B, RSV, PIV, measles virus, rhinovirus, adenovirus, HMPV, SARS virus, vaccinia virus, cowpox virus, ectomelia virus, monkeypox virus, rabbitpox virus, HBV, HCV, papillomavirus, BK virus, VEE virus, Rift Valley fever virus, Tavaribe virus, Yellow fever virus, West Nile virus, dengue virus, PTV or Pichinde virus. 
     
     
         43 . The method of  claim 42 , wherein the viral infection is infection with HCV or dengue virus. 
     
     
         44 . The method of  claim 39 , which further comprises administration of one or more additional anti-viral agents. 
     
     
         45 . The method of  claim 44 , wherein the additional anti-viral agent is an interferon, a protease inhibitor, an integrase inhibitor, a reverse transciptase inhibitor, or a combination thereof. 
     
     
         46 . The method of  claim 44 , wherein the additional anti-viral agent is an interferon, ribavirin or a combination thereof. 
     
     
         47 . The method of  claim 46 , wherein the interferon is interferon type III, interferon type II, interferon type I, peginterferon alfa-2a, peginterferon alfa-2b, standard interferon alfa-2a, standard interferon alfa-2b, consensus interferon, interferon alfacon-1, ALBUFERON, omega interferon, interferon gamma-1b, lymphoblastoid interferon tau, or a combination thereof. 
     
     
         48 . The method of  claim 39 , wherein the microbial infection is a bacterial infection. 
     
     
         49 . The method of  claim 48 , wherein the bacterial infection is selected from  Helicobacter pyloris, Borelia burgdorferi, Legionella pneumophilia, Mycobacteria tuberculosis, M. avium, M. intracellulare, M. kansaii, M. gordonae, Staphylococcus aureus, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Streptococcus faecalis, Streptococcus bovis, Streptococcus pneumoniae, Haemophilus influenzae, Bacillus antracis, corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, Clostridium perfringers, Clostridium tetani, Enterobacter aerogenes, Klebsiella pneumoniae, Pasturella multocida, Fusobacterium nucleatum, Streptobacillus moniliformis, Treponema pallidium, Treponema pertenue, Leptospira, Rickettsia, Actinotnyces israelli  or a combination thereof. 
     
     
         50 . The method of  claim 49 , wherein the bacterial infection is  Mycobacteria tuberculosis.    
     
     
         51 . The method of  claim 39 , wherein the microbial infection is a fungal infection. 
     
     
         52 . The method of  claim 51 , wherein the fungal infection is an infection with aspergilliosis, crytococcosis, sporotrichosis, coccidioidomycosis, paracoccidioidomycosis, histoplasmosis, blastomycosis, zygomycosis or candidiasis. 
     
     
         53 . The method of  claim 39 , wherein the microbial infection is a parasitic or protozoal infection. 
     
     
         54 . The method of  claim 53 , wherein the parasitic or protozoal infection is an infection with  P. falcifarium, P. ovale, P. vivax, P. malariae, L. donovari, L. inlantum, L. aethiopica, L. major, L. tropica, L. mexicana, L. braziliensis, T. Gondii, B. microti, B. divergens, B. coli, B. hominis, C. parvum, C. cayetanensis, D. fragilis, E. histolytica, I. belli, S. mansonii, S. haematobium, Trypanosoma  ssp.,  Toxoplasma  ssp.,  O. volvulus, Babesia bovis, Babesia canis, Banesia Gibsoni, Besnoitia darlingi, Cytauxzoon felis, Eimeria  ssp.,  Hammondia  ssp.  T. canis, Cestoda, Theileria  ssp. or a combination thereof. 
     
     
         55 . The method of  claim 53 , wherein the parasitic or protozoal infection causes malaria, babesiosis, trypanosomiasis, American trypanosomiasis, leishmaniasis, toxoplasmosis, meningoencephalitis, keratitis, amebiasis, giardiasis, cryptosporidiosis, isosporiasis, cyclosporiasis, microsporidiosis, ascariasis, trichuriasis, ancylostomiasis, strongyloidiasis, toxocariasis, trichinosis, lymphatic filariasis, onchocerciasis, filariasis schistosomiasis or dermatitis caused by animal schistosomes. 
     
     
         56 . The method of  claim 55 , wherein the parasitic or protozoal infection causes malaria. 
     
     
         57 . The method of  claim 55 , wherein the parasitic or protozoal infection causes leishmaniasis, babesiosis, toxoplasmosis or trypanosomiasis. 
     
     
         58 . The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable form thereof.