FAST-DISSOCIATING DOPAMINE 2 RECEPTOR ANTAGONISTS

摘要

The present invention relates to 4-aryl-6-piperazin-1-yl-3-substituted-pyridazines that are fast dissociating dopamine 2 receptor antagonists, processes for preparing these compounds, pharmaceutical compositions comprising these compounds as an active ingredient. The compounds find utility as medicines for treating or preventing central nervous system disorders, for example schizophrenia, by exerting an antipsychotic effect without motor side effects.

主权项

1. A compound of formula (I) or a stereoisomeric form thereof, wherein R1 is chloro, trifluoromethyl or cyano; R2 is phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C1-4alkyl, C1-4alkyloxy, C1-4alkylsulfonyl, perfluoroC1-4alkyl, perfluoroC1-4alkyloxy, diC1-4alkylamino, hydroxyl, and phenyl optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, C1-4alkyl and perfluoroC1-4alkyl; thienyl; thienyl substituted with 1 or 2 substituents each independently selected from the group consisting of halo and C1-4alkyl; naphthyl; pyridinyl; pyrrolyl; benzothiazolyl; indolyl; quinolinyl; C3-8cycloalkyl; or C5-7cycloalkenyl; R3 is hydrogen, C1-4alkyl, C1-4alkyloxy or halo; R4 and R5 are each independently hydrogen or C1-4alkyl, or R4 and R5 together form C1-4alkanediyl; n is 1 or 2; and R6 is hydrogen, C1-4alkyl, hydroxyC2-4alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, pyridinylmethyl, or phenylmethyl optionally substituted on the phenyl with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C1-4alkyl, C1-4alkyloxy, C1-4alkylsulfonyl, perfluoroC1-4alkyl, perfluoroC1-4alkyloxy and diC1-4alkylamino; or R5 and R6 together form C2-5alkanediyl; or a pharmaceutically acceptable salt or solvate thereof.