New N-acyl-5,6,7, (8-substituted) -tetrahydro- [1,2,4] -triazolo [4,3-a] chiral pyrazines, as selective NK-3 receptor antagonists, pharmaceutical composition and methods for use in disorders mediated by the NK-3 receptor
A compound of Formula I: ** Formula ** and pharmaceutically acceptable salts and solvates thereof, wherein Ar1 is unsubstituted thiophene-2-yl, unsubstituted phenyl, or 4-fluorophenyl； R1 is H or methyl； Ar2 is of general Formula (i), (ii) or (iii): ** Formula ** wherein R2 is alkyl of 1 to 4 linear or branched carbon atoms, haloalkyl of 1 to 2 carbon atoms, alkenyl of 2 at 3 linear or branched carbon atoms, cycloalkyl of 3 to 4 carbon atoms or cycloalkyl di (alkyl of 1 to 2 carbon atoms) amino； X1 is N or C-R6 where R6 is H, fluorine or alkyl of 1 to 2 carbon atoms； X2 is O or S； X3 is N, or X3 is CH with the proviso that X1 is N and X2 is N-R7 where R7 is alkyl of 1 to 3 linear or branched carbon atoms or cyclopropyl； R3 is alkyl of 1 to 4 linear or branched carbon atoms or cycloalkyl of 3 to 4 carbon atoms； X4 is N or C-R8, where R8 is H or alkyl of 1 to 2 carbon atoms； X5 is O or S； X6 is N, or X6 is CH with the proviso that X4 is N and X5 is N-R9 where R9 is alkyl of 1 to 3 linear or branched carbon atoms or cyclopropyl； R4 is halo, cyano, methyl or hydroxyl； R5 is H or halo； with the proviso that when Ar2 is of Formula (iii), then R1 is methyl； and the compound of Formula I is not (3- (2-isobutylthiazol-4-yl) -5,6-dihydro- [1,2,4] triazolo [4,3-a] pyrazin-7 (8H) -yl ) (4- (thiophen-2-yl) phenyl) methanone； [1,1'-biphenyl] -4-yl (8-methyl-3- (6-methylpyridin-2-yl) -5,6-dihydro- [1,2,4] triazolo [4,3-a] pyrazin-7 (8H) -yl) methanone； (8-methyl-3- (6-methylpyridin-2-yl) -5,6-dihydro- [1,2,4] triazolo [4,3-a] pyrazin-7 (8H) -yl) (4- (thiophen-2-yl) phenyl) methanone.Un compuesto de Fórmula I: **Fórmula** y sales y solvatos farmacéuticamente aceptables del mismo, en donde Ar1 es tiofen-2-ilo no sustituido, fenilo no sustituido, o 4-fluorofenilo； R1 es H o metilo； Ar2 es de Fórmula general (i), (ii) o (iii): **Fórmula** en donde R2 es alquilo de 1 a 4 átomos de carbono lineal o ramificado, haloalquilo de 1 a 2 átomos de carbono, alquenilo de 2 a 3 átomos de carbono
