Design, synthesis, and evaluation of tetrasubstituted pyridines as potent 5-HT2CReceptor agonists

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ROUQUET, Guy, MOORE, Dianna E., SPAIN, Malcolm, ALLWOOD, Daniel, BATTILOCCHIO, Claudio, BLAKEMORE, David C., FISH, Paul V., JENKINSON, Stephen, JESSIMAN, Alan S., LEY, Steven V., MCMURRAY, Gordon and STORER, R. Ian (2015). Design, synthesis, and evaluation of tetrasubstituted pyridines as potent 5-HT2CReceptor agonists. ACS Medicinal Chemistry Letters, 6 (3), 329-333. [Article]

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10759:562479

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10759:562479

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Abstract

A series of pyrido[3,4-d]azepines that are potent and selective 5-HT2C receptor agonists is disclosed. Compound 7 (PF-04781340) is identified as a suitable lead owing to good 5-HT2C potency, selectivity over 5-HT2B agonism, and in vitro ADME properties commensurate with an orally available and CNS penetrant profile. The synthesis of a novel bicyclic tetrasubstituted pyridine core template is outlined, including rationale to account for the unexpected formation of aminopyridine 13 resulting from an ammonia cascade cyclization.

More Information

Official URL:

http://pubs.acs.org/doi/abs/10.1021/ml500507v

Research Institute, Centre or Group - Does NOT include content added after October 2018:

Biomedical Research Centre

Page Range:

329-333

Identifiers

Identification Number:

10.1021/ml500507v

ORCID for Daniel Allwood: