The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds

Abstract

Compounds 7, 8, and 9, derived from the novel scaffolds 3, 5, and 6, were synthesized and evaluated in vitro. The b,c→c,d shift of the E-phenyl ring resulted in a large decrease (ca. 20- to 1000-fold) in binding to the 5-HT2A, 5-HT2C and H2, receptors, and a modest decrease (ca. 10- to 20-fold) in binding to the 5-HT5A, D2, D5, and α1D, receptors. The b,c→d,e shift resulted in a large decrease in binding to the 5-HT1D, 5-HT2C, 5-HT6, and H1 receptors, a modest decrease in binding to 5-HT1A, 5-HT5A and D2, D5, α2B, and H2 receptors, and a large increase in affinity to the 5-HT3, 5-HT6, and σ1 receptors.

Keywords: Dopamine; Gamma carboline; Histamine; Pyridoindolobenzazepine; Serotonin.