Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.
Basic Information
ID: ALA3425406
Journal: ACS Med Chem Lett
Title: Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.
Authors: Rouquet G, Moore DE, Spain M, Allwood DM, Battilocchio C, Blakemore DC, Fish PV, Jenkinson S, Jessiman AS, Ley SV, McMurray G, Storer RI.
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.
CiteXplore: 25815155
DOI: 10.1021/ml500507v
Patent ID: ┄