Repository logo
 

Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.


Change log

Authors

Rouquet, Guy 
Moore, Dianna E 
Spain, Malcolm 
Allwood, Daniel M 
Battilocchio, Claudio  ORCID logo  https://orcid.org/0000-0002-4601-8527

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.

Description

Keywords

5-HT2C receptor agonist, CNS penetration, Tetrasubstituted pyridines, pyrido[3,4-d]azepine

Journal Title

ACS Med Chem Lett

Conference Name

Journal ISSN

1948-5875
1948-5875

Volume Title

6

Publisher

American Chemical Society (ACS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/K009494/1)
Engineering and Physical Sciences Research Council (EP/K039520/1)
We would like to thank the EPSRC (SVL, grant nº EP/K0099494/1 and nº EP/K039520/1) for financial support.