MK-8133的鉴定：一种具有良好开发特性的食欲素-2选择性受体拮抗剂。
Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties.
作者信息
Kuduk Scott D, Skudlarek Jason W, DiMarco Christina N, Bruno Joseph G, Pausch Mark H, O'Brien Julie A, Cabalu Tamara D, Stevens Joanne, Brunner Joseph, Tannenbaum Pamela L, Garson Susan L, Savitz Alan T, Harrell Charles M, Gotter Anthony L, Winrow Christopher J, Renger John J, Coleman Paul J
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
出版信息
Bioorg Med Chem Lett. 2015 Jun 15;25(12):2488-92. doi: 10.1016/j.bmcl.2015.04.066. Epub 2015 Apr 29.
Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype. Judicious selection of the substituents on the pyridine ring and benzamide groups led to 6b; which was highly potent, OX2R selective, and exhibited excellent development properties.
食欲素受体拮抗剂已显示出作为治疗失眠及相关疾病的新范例的临床疗效。在此，与双重食欲素受体拮抗剂菲洛雷生相关的分子被转化为对OX2R亚型具有选择性的化合物。对吡啶环和苯甲酰胺基团上取代基的明智选择产生了6b；其具有高效力、OX2R选择性，并表现出优异的开发特性。
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