Synthesis and D-2-like binding affinity of 4,5-dihydro-1H-benzo[g]indole-3-carboxamide derivatives as conformationally restricted 5-phenyl-pyrrole-3-carboxamide analogs

A series of 4,5-dihydro-1H-benzo[g]-indole-3-carboxamide derivatives 2a-g w ere synthesized as conformationally restricted analogs of the dopamine D-2- like 5-phenylpyrrole-3-carboxamide ligands and evaluated for their affinity for the dopamine D-2-like receptors. In this series, N3-[(1-ethyltetrahydr o-1H-2-pyrrolyl)methyl]-4,5-dihydro-1H-benzo[g]indole-3-carboxamide (2a) sh owed the highest affinity for D-2-like receptors (IC50 = 160 nM). Replaceme nt of the N-(1-ethyl-2-pyrrolidinyl)methyl side chain with a 2-(N,N-diethyl amino)ethyl or a 1-benzyl-4-piperidinyl group (2b, 2d) decreased affinity f or the D-2-like receptor. The other compounds tested were found to be devoi d of D-2-like binding affinity. (C) 1998 Elsevier Science S.A. All rights r eserved.