Exploration of synthetic approaches and pharmacological evaluation of PNU-69176E and its stereoisomer as 5-HT2C receptor allosteric modulators.

ABSTRACT: Allosteric modulators of the serotonin (5-HT) 5-HT(2C) receptor (5-HT(2C)R) present a unique drug design strategy to augment the response to endogenous 5-HT in a site- and event-specific manner with great potential as novel central nervous system probes and therapeutics. To date, PNU-69176E is the only reported selective positive allosteric modulator for the 5-HT(2C)R. For the first time, an optimized synthetic route to readily access PNU-69176E (1) and its diastereomer 2 has been established in moderate to good overall yields over 10 steps starting from commercially available picolinic acid. This synthetic approach not only enables a feasible preparation of a sufficient amount of 1 for use as a reference compound for secondary pharmacological studies, but also provides an efficient synthe

SUBMITTER: Ding C 

PROVIDER: S-EPMC3400380 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature