Triazole ACC inhibitors and uses thereof

Abstract

The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or agriculturally acceptable salt thereof, wherein: 
         X is —O—, —S—, or —NR—; 
         R 1  is hydrogen, C 1-4  aliphatic optionally substituted with 1-4 halogen, —OR, —SR, —N(R) 2 , —N(R)C(O)R, —C(O)N(R) 2 , —N(R)C(O)N(R) 2 , —N(R)C(O)OR, —OC(O)N(R) 2 , —N(R)S(O) 2 R, —S(O) 2 N(R) 2 , —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, or —S(O) 2 R; 
         each instance of R 2 , R 6 , R 7 , and R 8  is independently oxo; halogen; —CN; —OR; —R a , —SR; —N(R) 2 ; —N(R)C(O)R; —C(O)N(R) 2 ; —N(R)C(O)N(R) 2 ; —N(R)C(O)OR; —OC(O)N(R) 2 ; —N(R)S(O) 2 R; —S(O) 2 N(R) 2 ; —C(O)R; —C(O)OR; —OC(O)R; —S(O)R; or —S(O) 2 R; 
         each R is independently hydrogen or R a ; 
         each R a  is independently an optionally substituted group selected from C 1-6  aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; 
         L 1  is a covalent bond; a 1-6 membered straight or branched bivalent hydrocarbon chain; cyclopropylenyl; cyclobutylenyl; or oxetanylenyl; 
         L 2  is a covalent bond or a 1-6 membered straight or branched bivalent hydrocarbon chain; wherein L 2  is substituted by n instances of R 9 ; 
         R 3  is —OR, —C(O)OR, —N(R)C(O)OR, —OC(O)N(R) 2 , —C(O)N(R)OR, —C(O)NH 2 , —C(O)NHR a , C(O)N(R a ) 2 , or —C(O)Hy; 
         Hy is a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein Hy is substituted by p instances of R 6 ; 
         R 4  is selected from a 3-8 membered monocyclic saturated or partially unsaturated carbocyclic ring, a 4-8 membered monocyclic saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, an 8-10 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein R 4  is substituted by q instances of R 7 ; 
         each R 5  is independently hydrogen, C 1-4  aliphatic, a 3-8 membered monocyclic saturated or partially unsaturated carbocyclic ring, a 4-8 membered monocyclic saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, an 8-10 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein each R 5  is substituted with r instances of R 8 ; 
         each R 9  is independently oxo or —OR 5 ; 
         m is 0, 1, 2, or 3; 
         n is 0, 1, or 2; 
         p is 0, 1, 2, 3, or 4; 
         q is 0, 1, 2, 3, 4, or 5; and 
         r is 0, 1, 2, 3, or 4. 
       
     
     
         2 .- 26 . (canceled)