Synthesis of functionalized 1,8-naphthyridinones and their evaluation as novel, orally active CB1 receptor inverse agonists

John S Debenham; Christina B Madsen-Duggan; Thomas F Walsh; Junying Wang; Xinchun Tong; George A Doss; Julie Lao; Tung M Fong; Marie-Therese Schaeffer; Jing Chen Xiao; Cathy R-R C Huang; Chun-Pyn Shen; Yue Feng; Donald J Marsh; D Sloan Stribling; Lauren P Shearman; Alison M Strack; D Euan MacIntyre; Lex H T Van der Ploeg; Mark T Goulet

doi:10.1016/j.bmcl.2005.10.028

Synthesis of functionalized 1,8-naphthyridinones and their evaluation as novel, orally active CB1 receptor inverse agonists

Bioorg Med Chem Lett. 2006 Feb;16(3):681-5. doi: 10.1016/j.bmcl.2005.10.028. Epub 2005 Nov 2.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. john_debenham@merck.com

PMID: 16263284
DOI: 10.1016/j.bmcl.2005.10.028

Abstract

Synthesis, SAR, and binding affinities are described for a new class of 1,8-naphthyridinone CB1 receptor specific inverse agonists. Food intake, knockout mouse, and pharmacokinetic evaluation of 14 indicate that this compound is an effective orally active modulator of CB1.

Publication types

Evaluation Study

MeSH terms

Administration, Oral
Animals
Binding Sites
Eating / drug effects*
Mice
Mice, Knockout
Models, Chemical
Naphthyridines / chemical synthesis
Receptor, Cannabinoid, CB1 / agonists
Receptor, Cannabinoid, CB1 / antagonists & inhibitors*

Substances

Naphthyridines
Receptor, Cannabinoid, CB1