ACC inhibitors and uses thereof
The present invention provides 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, an agriculturally acceptable salt, stereoisomer, or mixture of stereoisomers thereof, wherein:
X is S;
Q 1 is O;
Q 2 is O;
R 1 is hydrogen, halogen, —CN, —NO 2 , —R 6 , —OR, or —SR;
R 2 is hydrogen, halogen, —R 6 , —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, S(O) 2 R, or Hy; or
R 1 and R 2 may optionally be taken together to form an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclo-, or heterocyclo-, benzo-, or a 5-6 membered heteroarylo-fused ring;
Hy is an optionally substituted ring selected from a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 7-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
each R is independently selected from hydrogen, deuterium, and 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 aryl ring; a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 7-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
L 1 is a covalent bond or an optionally substituted straight or branched bivalent C 1-6 hydrocarbon chain;
R 3 is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from N, O, S, S(O), and S(O) 2 ; wherein R 3 is substituted with m instances of —R 5 ;
L 2 is a straight or branched bivalent C 1-6 hydrocarbon chain, wherein L 2 is substituted with p instances of —R 7 ;
R 4 is hydrogen or an optionally substituted ring selected from a 3-10 membered saturated or partially unsaturated monocyclic carbocyclic ring; phenyl; a 6-10 membered bicyclic saturated, partially unsaturated, or aryl ring; a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 7-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each R 4 may additionally be optionally substituted with n instances of —R 8 ;
each instance of R 5 is independently oxo, —R 6 , —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)SO 2 R, —SO 2 N(R) 2 , —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, and —S(O) 2 R; or
two instances of R 5 , together with the atom(s) to which they are attached, form an optionally substituted 3-10 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
each R 6 is independently selected from deuterium, and 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 aryl ring; a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 7-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
each instance of R 7 is independently selected from oxo, —R 6 , —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)SO 2 R, —SO 2 N(R) 2 , —C(O)R, —C(O)OR, —OC(O)R, —S(O)R, and —S(O) 2 R;
each R 8 is independently halogen, —R 6 , —OR, —SR, —N(R) 2 or deuterium;
each of m, n, and p is independently 0-5.
2. The compound of claim 1 , wherein R 3 (R 5 ) m , taken together, is:
3. The compound of claim 1 , wherein R 3 (R 5 ) m , taken together, is:
4. The compound of claim 1 , wherein R 1 is methyl.
5. The compound of claim 1 , wherein R 2 is Hy.
6. The compound of claim 5 , wherein Hy is:
7. The compound of claim 1 , wherein L 1 is a covalent bond.
8. The compound of claim 1 , wherein L 2 is ethylene, substituted with 1-2 instances of R 7 .
9. The compound of claim 8 , wherein L 2 (R 7 ) p taken together, is:
wherein # represents the point of attachment to R 4 .
10. The compound of claim 9 , wherein L 2 (R 7 ) p taken together, is:
wherein # represents the point of attachment to R 4 .
11. The compound of claim 1 , wherein R 4 (R 8 ) n , taken together is:
12. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof.
13. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
14. An agricultural composition comprising a compound according to claim 1 , or an agriculturally acceptable salt thereof, and an agriculturally acceptable carrier, optionally comprising an adjuvant, optionally comprising one or more additional pesticides, and optionally comprising one or more biological control agents, microbial extracts, natural products, plant growth activators or plant defense agents, or mixtures thereof.
15. A method of controlling agricultural fungal pathogens, the method comprising administering the composition of claim 14 to a plant, a seed or soil.
16. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof.
17. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof.