Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists

Michael M-C Lo; Harry R Chobanian; Oksana Palyha; Yanqing Kan; Theresa M Kelly; Xiao-Ming Guan; Marc L Reitman; Jasminka Dragovic; Kathryn A Lyons; Ravi P Nargund; Linus S Lin

doi:10.1016/j.bmcl.2011.02.011

Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists

Bioorg Med Chem Lett. 2011 Apr 1;21(7):2040-3. doi: 10.1016/j.bmcl.2011.02.011. Epub 2011 Feb 25.

Authors

Michael M-C Lo¹, Harry R Chobanian, Oksana Palyha, Yanqing Kan, Theresa M Kelly, Xiao-Ming Guan, Marc L Reitman, Jasminka Dragovic, Kathryn A Lyons, Ravi P Nargund, Linus S Lin

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]

PMID: 21354793
DOI: 10.1016/j.bmcl.2011.02.011

Abstract

Bombesin receptor subtype-3 (BRS-3) is an orphan G-protein coupled receptor belonging to the subfamily of bombesin-like receptors. BRS-3 is implicated in the development of obesity and diabetes. We report here small-molecule agonists that are based on a 4-(alkylamino)pyridine-3-sulfonamide core. We describe the discovery of 2a, which has mid-nanomolar potency, selectivity for human BRS-3 versus the other bombesin-like receptors, and good bioavailability.

MeSH terms

Animals
Biological Availability
Hydrogen Bonding
Male
Pyridines / chemistry*
Rats
Rats, Sprague-Dawley
Receptors, Bombesin / agonists*
Sulfonamides / chemistry
Sulfonamides / pharmacokinetics
Sulfonamides / pharmacology*
Sulfonylurea Compounds / chemistry
Sulfonylurea Compounds / pharmacokinetics
Sulfonylurea Compounds / pharmacology*

Substances

Pyridines
Receptors, Bombesin
Sulfonamides
Sulfonylurea Compounds
bombesin receptor subtype 3
pyridine