Cyanoindole Derivatives as Highly Selective Dopamine D4Receptor Partial Agonists: Solid-Phase Synthesis, Binding Assays, and Functional Experiments

Publisher Website
Google Scholar
Abstract
Traceless linking of diethoxymethyl (DEM)-protected 5- and 6-cyanoindoles and subsequent incorporation of phenylpiperazine derivatives led to the 2- and 3-piperazinylmethyl-substituted cyanoindoles 3a − m. Dopamine receptor binding studies on the final products 3a − m clearly indicated strong and selective recognition of the D4 subtype which is known as a promising target for the treatment of neuropsychiatric disorders. The most interesting binding properties were observed for the 2-aminomethyl-5-cyanoindoles FAUC 299 (3f) and FAUC 316 (3j) (Ki = 0.52 and 1.0 nM, respectively) when the fluoro derivative 3j proved extraordinary selectivity over D1, D2long, D2short, and D3 (>8600). To determine ligand efficacy, mitogenesis experiments were performed indicating partial agonist effects for the test compounds 3f,j (35% and 30%, when compared to the full agonist quinpirole).

This publication has 13 references indexed in Scilit: