A New Synthesis of Indole 5‐Carboxylic Acids and 6‐Hydroxy‐indole‐5‐carboxylic Acids in the Preparation of an o‐Hydroxylated Metabolite of Vilazodone.

Abstract

The synthesis of a major metabolite (I) of vilazodone using a Japp-Klingemann type Frischer-indole synthesis protocol is presented. -(HEINRICH*, T.; BOETTCHER, H.; Bioorg. Med.

Vilazodone: A 5‐HT1A Receptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders

“…The synthesis of the hydroxylated metabolite (Fig. 1) was reported by Heinrich and Böttcher [40] who also reported a reduction in the dual activity of this molecule (although no data were presented). Unfortunately, to these authors knowledge, no further information is available on the hydroxylated metabolite or any other minor metabolites, so it is difficult to speculate on the likely contribution of the metabolites to vilazodone's in vivo and subsequent clinical profiles.…”

“…Vilazodone was synthesized by coupling ethyl 5-(piperazino)benzofuran-2-carboxylate and 3-(4chlorobutyl)-1H-indole-5-carbonitrile. Several patents and publications describe the chemical synthesis, production of intermediates, and ultimately the identification of vilazodone and its active metabolites [38][39][40].…”

Vilazodone Hydrochloride, a Combined SSRI and 5-HT1A Receptor Agonist for Major Depressive Disordersts

“…This may be one reason for the modest efficacy of the compound in vivo in clinical trials in contrast to its in vitro and in vivo (animal) activity. 9 The principal CYP450 isozyme involved in vilazodone metabolism is 3A4 in humans while isozymes 2C19 and 2D6 play only a minor role. In vitro studies suggest that isozymes 1A2, 2A6, 2C9, and 2E1 contribute to a minimal extent.…”