Identification of A Butyrophenone Analog as a Potential Atypical Antipsychotic Agent: 4-4-(4-Chlorophenyl)-14-diazepan-1-yl-1-(4-fluorophenyl)butan-1-one

摘要

The synthesis and exploration of novel butyrophenones have led to the identification of a diazepane analog of haloperidol, 4-[4-(4-Chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one (Compound >13) with an interesting multireceptor binding profile. Compound >13 was evaluated for its binding affinities at DA subtype receptors, 5HT subtype receptors, H-1, M-1 receptors and at NET, DAT and SERT transporters. At each of these receptors, compound >13 was equipotent or better than several of the standards currently in use. In in vivo mouse and rat models to evaluate its efficacy and propensity to elicit catalepsy and hence EPS in humans, compound >13 showed similar efficacy as clozapine and did not produce catalepsy at five times its ED50 value.