Indole AHR inhibitors and uses thereof
The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
1. A compound selected from any one of formulae IX-a, IX-b and IX-c:
or a pharmaceutically acceptable salt thereof, wherein X is N or CH;
each or R x , R y , and R z is independently selected from R, halogen, cyano, nitro, —OR, —SR, —N(R) 2 , —N(R)C(O)R, —C(O)N(R) 2 , —C(O)N(R)OR, —N(R)C(O)N(R) 2 , —N(R)C(O)OR, —OC(O)N(R) 2 , —N(R)SO 2 R, —SO 2 RN(R) 2 , —C(O)R, —C(O)OR, —OC(O)R, —C(O)OR, —S(O)R, or —SO 2 R, or:
two R x on the same carbon are taken together to form ═O or ═S; or:
two R y on the same carbon are taken together to form ═O or ═S;
each R is independently hydrogen, deuterium, or 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; or two R on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or aromatic ring having 1-2 heteroatoms in addition to the nitrogen independently selected from oxygen, nitrogen, or sulfur;
each p is independently 0, 1, or 2, as valency will allow; and
each of m and n is independently 1, 2, 3, 4, or 5.
2. A compound selected from any one of formulae X-a, X-b, X-c, X-d, X-e, X-f, X-g, X-h and X-i:
or a pharmaceutically acceptable salt thereof, wherein X is N or CH;
each or R x , R y , and R z is independently selected from R, halogen, cyano, nitro, —OR, —SR, —N(R) 2 , —N(R)C(O)R, —C(O)N(R) 2 , —C(O)N(R)OR, —N(R)C(O)N(R) 2 , —N(R)C(O)OR, —OC(O)N(R) 2 , —N(R)SO 2 R, —SO 2 RN(R) 2 , —C(O)R, —C(O)OR, —OC(O)R, —C(O)OR, —S(O)R, or —SO 2 R, or:
two R x on the same carbon are taken together to form ═O or ═S; or:
two R y on the same carbon are taken together to form ═O or ═S;
each R is independently hydrogen, deuterium, or 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; or two R on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or aromatic ring having 1-2 heteroatoms in addition to the nitrogen independently selected from oxygen, nitrogen, or sulfur;
each p is independently 0, 1, or 2, as valency will allow; and
each of m and n is independently 1, 2, 3, 4, or 5.
3. The compound according to claim 2 wherein the compound is selected from any one of formulae XI-a, XI-b, XI-c, XI-d, XI-e, XI-f, XI-g, XI-h and XI-i:
or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 2 wherein the compound is selected from any one of formulae XII-a, XII-b and XI-c:
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 2 wherein the compound is selected from:
or a pharmaceutically acceptable salt thereof.
6. A composition comprising a compound according to claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
7. A composition comprising a compound according to claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
8. The compound according to claim 2 wherein the compound is selected from
or a pharmaceutically acceptable salt thereof.
9. A composition comprising a compound according to claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
10. A compound, wherein the compound is
or a pharmaceutically acceptable salt thereof.
11. A composition comprising a compound according to claim 10 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
12. A compound, wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. A composition comprising a compound according to claim 12 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
14. A compound, wherein the compound is
or a pharmaceutically acceptable salt thereof.
15. A composition comprising a compound according to claim 14 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
16. A compound, wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. A composition comprising a compound according to claim 16 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.