title: The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization.
abstract: Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and obesity. We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-7725(1) Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. harry_chobanian@merck.com
authors.forename: Harry R
authors.initials: HR
authors.lastname: Chobanian
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lanza
authors.forename: Marc
authors.initials: M
authors.lastname: Chioda
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Kelly
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Kan
authors.forename: Oksana
authors.initials: O
authors.lastname: Palyha
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Guan
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Metzger
authors.forename: Katie
authors.initials: K
authors.lastname: Raustad
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Wang
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: Judith N
authors.initials: JN
authors.lastname: Gorski
authors.forename: Randy
authors.initials: R
authors.lastname: Miller
authors.forename: Jianmei
authors.initials: J
authors.lastname: Pang
authors.forename: Kathy
authors.initials: K
authors.lastname: Lyons
authors.forename: Jasminka
authors.initials: J
authors.lastname: Dragovic
authors.forename: Jian G
authors.initials: JG
authors.lastname: Ning
authors.forename: Wes A
authors.initials: WA
authors.lastname: Schafer
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Welch
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gong
authors.forename: Ying-Duo
authors.initials: YD
authors.lastname: Gao
authors.forename: Viktor
authors.initials: V
authors.lastname: Hornak
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Nargund
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D051379:Mice; D011485:Protein Binding; D051381:Rats; D018004:Receptors, Bombesin / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D013696:Temperature
chemical_list: D018004:Receptors, Bombesin; D013449:Sulfonamides; C107120:bombesin receptor subtype 3; D001569:Benzodiazepines