MK-7725的发现，一种用于治疗肥胖症的强效、选择性胃泌素释放肽受体亚型3激动剂。
Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity.
作者信息
Chobanian Harry R, Guo Yan, Liu Ping, Chioda Marc, Lanza Thomas J, Chang Linda, Kelly Theresa M, Kan Yanqing, Palyha Oksana, Guan Xiao-Ming, Marsh Donald J, Metzger Joseph M, Gorski Judith N, Raustad Kate, Wang Sheng-Ping, Strack Alison M, Miller Randy, Pang Jianmei, Madeira Maria, Lyons Kathy, Dragovic Jasminka, Reitman Marc L, Nargund Ravi P, Lin Linus S
机构信息
Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
出版信息
ACS Med Chem Lett. 2012 Jan 21;3(3):252-6. doi: 10.1021/ml200304j. eCollection 2012 Mar 8.
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.
摘要
对源自前所述手性苯并二氮杂卓磺酰胺系列的阻转异构体1的一系列化合物进行了广泛的构效关系研究，得到了一种强效、可穿透血脑屏障且具有选择性的化合物，该化合物在不同物种中均具有优异的临床前药代动力学特性。我们还描述了一种高通量小鼠药效学测定方法的应用，该方法可方便地评估药代动力学和脑内分布情况。
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