Thiadiazole analogs thereof and methods for treating SMN-deficiency-related-conditions

摘要

The present invention provides a compound of Formula (X) 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.

主权项

1. A compound, or salt thereof, which compound is represented by Formula (X) wherein A′ is phenyl which is substituted with 0, 1, 2, or 3 substituents independently selected from C1-C4alkyl, wherein 2 C1-C4alkyl groups can combine with the atoms to which they are bound to form a 5-6 membered ring and is substituted with 0 or 1 substituent selected from oxo, oxime and hydroxy, haloC1-C4alkyl, dihaloC1-C4alkyl, trihaloC1-C4alkyl, C1-C4alkoxy, C1-C4alkoxy-C3-C7cycloalkyl, haloC1-C4alkoxy, dihaloC1-C4alkoxy, trihaloC1-C4alkoxy, hydroxy, cyano, halogen, amino, mono-C1-C4alkylamino, di-C1-C4alkylamino, heteroaryl, C1-C4alkyl substituted with hydroxy, C1-C4alkoxy substituted with aryl, —C(O)NHC1-C4alkyl-heteroaryl, —NHC(O)—C1-C4alkyl-heteroaryl, C1-C4alkylC(O)NH-heteroaryl, C1-C4alkylNHC(O)-heteroaryl, 3-7 membered cycloalkyl, 5-7 membered cycloalkenyl and 5, 6 or 9 membered heterocycle containing 1 or 2 heteroatoms, independently, selected from S, O and N, wherein heteroaryl has 5, 6 or 9 ring atoms, 1, 2 or 3 ring heteroatoms selected from N, O and S, and substituted with 0, 1, or 2 substituents independently selected from oxo, hydroxy, nitro, halogen, C1-C4alkyl, C1-C4alkenyl, C1-C4alkoxy, C3-C7cycloalkyl, C1-C4alkyl-OH, trihaloC1-C4alkyl, mono-C1-C4alkylamino, di-C1-C4alkylamino, —C(O)NH2, —NH2, —NO2, hydroxyC1-C4alkylamino, hydroxyC1-C4alkyl, 4-7 member heterocycleC1-C4alkyl, aminoC1-C4alkyl, mono-C1-C4alkyl and di-C1-C4alkylaminoC1-C4alkyl; or A′ is 6 member heteroaryl having 1-3 ring nitrogen atoms, which 6 member heteroaryl is substituted by phenyl or a heteroaryl having 5 or 6 ring atoms, 1 or 2 ring heteroatoms independently selected from N, O and S, and substituted with 0, 1, or 2 substituents independently selected from C1-C4alkyl, mono-C1-C4alkylamino, di-C1-C4alkylamino, hydroxyC1-C4alkylamino, hydroxyC1-C4alkyl, aminoC1-C4alkyl, mono-C1-C4alkylaminoC1-C4alkyl and di-C1-C4alkylaminoC1-C4alkyl; or A′ is bicyclic heteroaryl having 9 to 10 ring atoms and 1, 2, or 3 ring heteroatoms independently selected from N, O or S, which bicyclic heteroaryl is substituted with 0, 1, or 2 substituents independently selected from oxo, cyano, halogen, hydroxy, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4alkoxy substituted with hydroxy, C1-C4alkoxy, amino, mono-C1-C4alkylamino and di-C1-C4alkylamino; B is