Pyridazinone compounds

摘要

The invention relates to pyridazinone and pyridone compounds having formula (I) or (I′), and pharmaceutically acceptable salts, hydrates, and solvates thereof (I) wherein R1/R4 and X and X3 are as defined in the claims. The invention further relates to their use as inhibitors of copper-containing amine oxidases. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds, pharmaceutically acceptable salts, hydrates, or solvates thereof.;

主权项

1. A pyridazinone compound of general formula (I′), or pharmaceutically acceptable salt, hydrate, or solvate thereof,wherein
X is N; R1 is phenyl, optionally substituted with R11, wherein R11 is selected from the group consisting of halogen, halo-C1-3-alkyl, and C1-6-alkoxy; R2 is H or triazolyl; (i) X3 is O or S, and R3 is selected from the group consisting of C2-6-alkenyl, and phenyl, said phenyl being optionally substituted one or more times with R31, each R31 is independently selected from the group consisting of halogen, halo-C1-3-alkyl and C1-6-alkoxy; or (ii) X3 is NR3′, and R3 and R3′ together with the nitrogen, to which they are attached, form a 5 or 6 membered saturated heterocyclic ring, —N3, or triazole, said triazole being optionally substituted with R32, wherein R32 is selected from the group consisting of phenyl, C1-6-alkyl, and —CO2(C1-3-alkyl); or R3′ is H or C1-3-alkyl, and R3 is selected from the group consisting of H; C1-6-alkyl; C2-6-alkenyl; C2-6-alkynyl; C3-6-cycloalkyl-C1-6-alkyl; C3-6-cycloalkyl; cyano-C1-6-alkyl; amino-C1-6-alkyl; benzyl; pyridyl saturated 5 or 6 membered heterocyclic ring having 1 to 2 heteroatoms selected from N, O, and S, and wherein said N is optionally substituted with C1-6-alkyl; R33R33′N—C1-6-alkylenyl; and phenyl, said phenyl being optionally substituted 1 to 3 times with R34; wherein R33 and R33′ are both C1-3-alkyl, or R33 and R33′ together with the nitrogen, to which they are attached, form a saturated 5 or 6 membered heterocyclic ring optionally comprising one further heteroatom selected from N, O, and S; each R34 is independently selected from the group consisting of NR35R35′, hydroxy and C1-6-alkoxy; or two adjacent R34 together with the carbon atoms, to which they are attached, form a 5 or 6 membered fused heterocyclic ring comprising 1 or 2 heteroatom(s) each independently selected from N, O and S; wherein R35 and R35′ are both H or C1-6-alkyl; or R35 and R35′ together with the nitrogen, to which they are attached, form a 5 or 6 membered saturated heterocyclic ring optionally further comprising as a ring member O, S, N, or NR36, wherein R36 is H, C1-6-alkyl or benzoyl; R4 is selected from the group consisting of —CN; —C(═O)X4R41; phenyl, wherein said phenyl is optionally substituted with R42; and an 5 or 6 membered unsaturated heterocyclic ring having 1 to 4 heteroatoms each independently selected from N, O and S and being optionally substituted one or more times with R43; wherein X4 is NH; and R41 is selected from the group consisting of H, C1-6-alkyl, R44R44′N—C1-6-alkylenyl, and —NHR45, wherein R44 and R44′ are both H or C1-6-alkyl; or R44 and R44′ together with the nitrogen, to which they are attached, form a 5 or 6 membered saturated heterocyclic ring; and R45 is H or imino-C1-6-alkyl; or X4 and R41 taken together form —N═CR46R47, wherein R46 is H or methyl, and R47 is di(C1-3-alkyl)amino; R42 is selected from the group consisting of halogen, halo-C1-3-alkyl, and C1-6-alkoxy; each R43 is independently selected from the group consisting of —OH, —SH, and methyl;excluding 5-phenoxy-2-phenyl-6-(1H-1,2,4-triazol-3-yl)pyridazin-3(2H)-one.