1,4-disubstituted pyridazine analogs thereof and methods for treating SMN-deficiency-related conditions
AssigneeNovartis AG
InventorsAtwood Kim Cheung, Donovan Noel Chin, Natalie Dales, Aleem Fazal, Timothy Brian Hurley, John Kerrigan, Gary O'Brien, Lei Shu, Robert Sun, Moo Je Sung
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Abstract
The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
Claims24
A method to treat spinal muscular atrophy Type I, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- A is 2-naphthyl optionally substituted at the 3 position with hydroxy and additionally substituted with 0, 1, or 2 substituents selected from hydroxy, cyano, halogen, C1-C4alkyl, C2-C4alkenyl, C1-C5alkoxy, wherein the alkoxy is unsubstituted or substituted with hydroxy, C1-C4alkoxy, amino, N(H)C(O)C1-C4alkyl, N(H)C(O)2 C1-C4alkyl, alkylene 4 to 7 member heterocycle, 4 to 7 member heterocycle and mono- and di-C1-C4alkylamino, and
- B is selected from the group consisting of
- wherein X is 0 or N(Me);
- and
- R17 is hydrogen or methyl.
A method to treat spinal muscular atrophy Type II, comprising administering to a subject in need thereof an effective amount of a compound according to Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- A is 2-naphthyl optionally substituted at the 3 position with hydroxy and additionally substituted with 0, 1, or 2 substituents selected from hydroxy, cyano, halogen, C1-C4alkyl, C2-C4alkenyl, C1-C5alkoxy, wherein the alkoxy is unsubstituted or substituted with hydroxy, C1-C4alkoxy, amino, N(H)C(O)C1-C4alkyl, N(H)C(O)2 C1-C4alkyl, alkylene 4 to 7 member heterocycle, 4 to 7 member heterocycle and mono- and di-C1-C4alkylamino;
- and
- B is selected from the group consisting of
- wherein X is O or N(Me);
- and
- R17 is hydrogen or methyl.
A method to treat spinal muscular atrophy Type III, comprising administering to a subject in need thereof an effective amount of a compound according to Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- A is 2-naphthyl optionally substituted at the 3 position with hydroxy and additionally substituted with 0, 1, or 2 substituents selected from hydroxy, cyano, halogen, C1-C4alkyl, C2-C4alkenyl, C1-C5alkoxy, wherein the alkoxy is unsubstituted or substituted with hydroxy, C1-C4alkoxy, amino, N(H)C(O)C1-C4alkyl, N(H)C(O)2 C1-C4alkyl, alkylene 4 to 7 member heterocycle, 4 to 7 member heterocycle and mono- and di-C1-C4alkylamino;
- and
- B is selected from the group consisting of
- wherein X is O or N(Me);
- and
- R17 is hydrogen or methyl.
A method to treat spinal muscular atrophy Type IV, comprising administering to a subject in need thereof an effective amount of a compound according to Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- A is 2-naphthyl optionally substituted at the 3 position with hydroxy and additionally substituted with 0, 1, or 2 substituents selected from hydroxy, cyano, halogen, C1-C4alkyl, C2-C4alkenyl, C1-C5alkoxy, wherein the alkoxy is unsubstituted or substituted with hydroxy, C1-C4alkoxy, amino, N(H)C(O)C1-C4alkyl, N(H)C(O)2 C1-C4alkyl, alkylene 4 to 7 member heterocycle, 4 to 7 member heterocycle and mono- and di-C1-C4alkylamino;
- and
- B is selected from the group consisting of
- wherein X is 0 or N(Me);
- and
- R17 is hydrogen or methyl.
Dependencies are inferred from the claim text.