1-H-pyrrolo[2,3-c]pyridine compounds
Compounds having the structure of Formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , and A are as defined in the specification; pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent Menin-mediated conditions; kits comprising such compounds and salts; and methods for manufacturing such compounds and salts.
1 . A compound that is(S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl) piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
or a pharmaceutically acceptable salt thereof.
2 . A compound that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl) piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
or a pharmaceutically acceptable salt thereof.
3 . The compound of claim 2 that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
4 . The salt of claim 2 that is the pharmaceutically acceptable salt of the compound that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
5 . A pharmaceutical composition comprising a compound that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
6 . The pharmaceutical composition of claim 5 comprising the compound that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
and one or more pharmaceutically acceptable excipients.
7 . The pharmaceutical composition of claim 5 comprising the pharmaceutically acceptable salt of the compound that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
and one or more pharmaceutically acceptable excipients.
8 . A method of treating leukemia in a subject suffering from or susceptible to the leukemia, wherein the method comprises administering to the subject a therapeutically effective amount of a compound that is (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
or a pharmaceutically acceptable salt thereof.
9 . The method of claim 8 , wherein the method comprises administering to the subject a therapeutically effective amount of a compound that is ((S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
10 . The method of claim 8 , wherein the method comprises administering to the subject a therapeutically effective amount of the pharmaceutically acceptable salt of the compound that is(S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-1-yl)-5-fluoro-N,N-diisopropylbenzamide having the structure:
11 . The method of claim 8 , wherein the leukemia is selected from the group consisting of acute myeloid leukemia and acute lymphoid leukemia.
12 . The method of claim 8 , wherein the leukemia is acute myeloid leukemia.
13 . The method of claim 8 , wherein the leukemia is selected from the group consisting of mixed-lineage leukemia (MLL)-rearranged leukemia and NPM1-mutant acute myeloid leukemia.
14 . The method of claim 9 , wherein the leukemia is selected from the group consisting of acute myeloid leukemia and acute lymphoid leukemia.
15 . The method of claim 9 , wherein the leukemia is acute myeloid leukemia.
16 . The method of claim 9 , wherein the leukemia is selected from the group consisting of mixed-lineage leukemia (MLL)-rearranged leukemia and NPM1-mutant acute myeloid leukemia.
17 . The method of claim 10 , wherein the leukemia is selected from the group consisting of acute myeloid leukemia and acute lymphoid leukemia.
18 . The method of claim 10 , wherein the leukemia is acute myeloid leukemia.
19 . The method of claim 10 , wherein the leukemia is selected from the group consisting of mixed-lineage leukemia (MLL)-rearranged leukemia and NPM1-mutant acute myeloid leukemia.