Heterocyclic amides useful as protein modulators
View Patent ↗Disclosed are compounds having the formula: wherein q, r, s, A, B, C, R A1 , R A2 , R B1 , R B2 , R C1 , R C2 , R 3 , R 4 , R 5 , R 6 , R 14 , R 15 , R 16 , and R 17 , are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.
1. A compound which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazole-5-carboxamide
having the structure of
or a tautomer thereof,
or a pharmaceutically acceptable salt thereof,
or a hydrate thereof.
2. The compound according to claim 1 , which is a pharmaceutically acceptable salt of (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazole-5-carboxamide, or a tautomer thereof.
3. The compound according to claim 1 , which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazole-5-carboxamide, or a tautomer thereof.
4. The compound according to claim 1 , which is (E)-1-((E)-4-((E)-5-carbamoyl-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-(3-morpholinopropoxy)-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide having the structure of
or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising a compound which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazole-5-carboxamide having the structure of
or a tautomer thereof,
or a pharmaceutically acceptable salt thereof,
or a hydrate thereof, and
a pharmaceutically acceptable excipient.
6. The pharmaceutical composition according to claim 5 , wherein the compound is
(E)-1-((E)-4-((E)-5-carbamoyl-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-(3-morpholinopropoxy)-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide having the structure of
or a pharmaceutically acceptable salt thereof.
7. A method of treating a STING-mediated disease or disorder comprising administering a therapeutically effective amount of a compound which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazole-5-carboxamide
having the structure of
or a tautomer thereof,
or a pharmaceutically acceptable salt thereof,
or a hydrate thereof,
to a human in need thereof.
8. The method according to claim 7 , wherein the compound is (E)-1-((E)-4-((E)-5-carbamoyl-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-(3-morpholinopropoxy)-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide having the structure of
or a pharmaceutically acceptable salt thereof.
9. The method according to claim 7 , wherein the STING-mediated disease or disorder is an infectious disease.
10. The method according to claim 9 , wherein the infectious disease is HIV.