Furo[2,3-b]pyridine-based cannabinoid-1 receptor inverse agonists: synthesis and biological evaluation. Part 1

John S Debenham; Christina B Madsen-Duggan; Richard B Toupence; Thomas F Walsh; Junying Wang; Xinchun Tong; Sanjeev Kumar; Julie Lao; Tung M Fong; 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; Mark T Goulet

doi:10.1016/j.bmcl.2009.12.065

Furo[2,3-b]pyridine-based cannabinoid-1 receptor inverse agonists: synthesis and biological evaluation. Part 1

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1448-52. doi: 10.1016/j.bmcl.2009.12.065. Epub 2010 Jan 4.

Authors

John S Debenham¹, Christina B Madsen-Duggan, Richard B Toupence, Thomas F Walsh, Junying Wang, Xinchun Tong, Sanjeev Kumar, Julie Lao, Tung M Fong, 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, Mark T Goulet

Affiliation

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

PMID: 20096577
DOI: 10.1016/j.bmcl.2009.12.065

Abstract

The synthesis, SAR and binding affinities of cannabinoid-1 receptor (CB1R) inverse agonists based on furo[2,3-b]pyridine scaffolds are described. Food intake, mechanism specific efficacy, pharmacokinetic, and metabolic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R.

MeSH terms

Animals
Benzopyrans
Dogs
Drug Design*
Furans / chemical synthesis*
Furans / chemistry
Furans / pharmacology
Haplorhini
Humans
Inhibitory Concentration 50
Mice
Mice, Knockout
Molecular Structure
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / pharmacology
Rats
Receptor, Cannabinoid, CB1 / agonists*
Receptor, Cannabinoid, CB1 / genetics
Structure-Activity Relationship

Substances

Benzopyrans
Furans
Pyridines
Receptor, Cannabinoid, CB1
furobenzopyranone