title: Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity.
abstract: Extensive structure-activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Harry R
authors.initials: HR
authors.lastname: Chobanian
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Marc
authors.initials: M
authors.lastname: Chioda
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lanza
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Kelly
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Kan
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Oksana
authors.initials: O
authors.lastname: Palyha
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Guan
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Marsh
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Metzger
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Judith N
authors.initials: JN
authors.lastname: Gorski
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Kate
authors.initials: K
authors.lastname: Raustad
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Wang
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Randy
authors.initials: R
authors.lastname: Miller
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Pang
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Madeira
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Kathy
authors.initials: K
authors.lastname: Lyons
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Dragovic
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Nargund
authors.affiliation: Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
keywords: BRS-3; Bombesin receptor subtype-3; MK-7725; agonist; atropisomer; benzodiazepine sulfonamide; obesity