title: Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. michael_lo@merck.com
authors.forename: Michael M-C
authors.initials: MM
authors.lastname: Lo
authors.forename: Harry R
authors.initials: HR
authors.lastname: Chobanian
authors.forename: Oksana
authors.initials: O
authors.lastname: Palyha
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Kan
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Kelly
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Guan
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Jasminka
authors.initials: J
authors.lastname: Dragovic
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Nargund
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001682:Biological Availability; D006860:Hydrogen Bonding; D008297:Male; D011725:Pyridines / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018004:Receptors, Bombesin / Q000819:agonists*; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D011725:Pyridines; D018004:Receptors, Bombesin; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; C107120:bombesin receptor subtype 3; C023666:pyridine