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.
A major metabolite of the potential antidepressant vilazodone formed in rat, dog, monkey and human liver microsomes is the 5-cyano-6-hydroxy-1H-indole derivative. For the construction of the salicyl-like substituted indole we adapted a synthesis of carmoxirole using Japp-Klingemann type Fischer-indole synthesis protocols. Functional group interconversion of carboxylic acid via carboxamide into cyanide was performed with methanesulfonic acid chloride.
Heinrich
Timo
T
Merck KGaA, Preclinical Pharmaceutical Research, Frankfurter Str. 250, 64293 Darmstadt, Germany. timo.heinrich@merck.de
Böttcher
Henning
H
D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002264:Carboxylic Acids; D006801:Humans; D006900:Hydroxylation; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D000069503:Vilazodone Hydrochloride
D000928:Antidepressive Agents; D001572:Benzofurans; D002264:Carboxylic Acids; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000069503:Vilazodone Hydrochloride; C071485:carmoxirole