Journal Papers Discovery and structure-activity relationship of a novel spirocarbamate series of NPY Y5 antagonists.


Abstract

A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development. Both compounds significantly inhibited the food intake induced by a Y5 selective agonist with minimal effective doses of 3mg/kg po.



Paper Details

Authors

C. Leslie,  J. Bentley,  M. Biagetti,  S. Contini,  R. Di Fabio,  D. Donati,  T. Genski,  S. Guery,  A. Mazzali,  G. Merlo ,  D. Pizzi,  F. Sacco,  C. Seri,  M. Tessari,  L. Zonzini,  L. Caberlotto

Publication

Bioorg Med Chem Lett., 20, , 6103-7

Download

http://www.sciencedirect.com/science/article/pii/S0960894X10011649

Language

English
.