Utilisation of heteroarene carboxamide as dopamine-D3 ligands for the treatment of CNS diseases

摘要

N-((4-Phenyl-piperazin-1-yl)-alkyl) 2-benzo-heterocyclyl-carboxamides (I) - (III) and N-((4-phenyl-piperazin-1-yl)-alkyl) 2-ferrocenyl-carboxamides (II) are new. Piperazine derivatives of formula (I) - (IV) (including salts of (I)) are new. [Image] n : 1-4; R : H, alkyl or halogen; and X : O or S; R1OH, alkoxy, alkenyl, alkynyl, aryl, acyl, alkoxycarbonyl or CN; and R2, R3H, OH, alkoxy, alkyl, alkenyl, alkynyl, aryl, halo, CF3, acyl, alkoxycarbonyl or CN; or R1H, alkyl, halo or CF3; R2OH, alkenyl, alkynyl, aryl, acyl, alkoxycarbonyl or CN; and R3H, OH, alkoxy, alkyl, alkenyl, alkynyl, aryl, halo, CF3, acyl, alkoxycarbonyl or CN; R21 - R23H, OH, alkoxy, alkyl, alkenyl, alkynyl, aryl, halo, CF3, acyl, alkoxycarbonyl or CN (provided that the compound N-4-(4-(2-methoxyphenyl)-piperazin-1-yl)-butyl-2-indolyl-carboxamide is excluded); R31 - R33H, OH, alkoxy, alkyl, alkenyl, alkynyl, aryl, halo, CF3, acyl, alkoxycarbonyl or CN; and R12, R13H, OH, alkoxy, alkyl, alkenyl, alkynyl, aryl, halo, CF3, acyl, alkoxycarbonyl or CN (the R12 and R13 groups optionally being combined). Provided that alkyl, alkenyl, alkynyl and aryl groups are all optionally substituted. An independent claim is also included for the preparation of (I) - (V). ACTIVITY : Antiaddictive; Antialcoholic; Antismoking; Neuroprotective; Antiparkinsonian; Vasotropic; Antidepressant; Neuroleptic; Ophthalmological; Nootropic; Tranquilizer. MECHANISM OF ACTION : Dopamine D3 receptor ligand. N-4-(4-(2-Methoxyphenyl)-piperazin-1-yl)-butyl-2-benzo(b)thiophene-carboxamide (Ia) had Ki 0.23 nM in a D3 receptor binding assay.