内酰胺类作为前列环素受体EP4亚型选择性激动剂。第1部分：2-吡咯烷酮类——立体化学及低级侧链优化。
Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization.
作者信息
Elworthy Todd R, Kertesz Denis J, Kim Woongki, Roepel Michael G, Quattrocchio-Setti Lina, Smith David B, Tracy Jahari Laurant, Chow Audrey, Li Fujun, Brill Emma R, Lach Leang K, McGee Daren, Yang Diana S, Chiou San-San
机构信息
Roche Palo Alto, Department of Medicinal Chemistry, 3431Hillview Avenue, Palo Alto, CA 94304-1397, USA.
出版信息
Bioorg Med Chem Lett. 2004 Apr 5;14(7):1655-9. doi: 10.1016/j.bmcl.2004.01.063.
A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP(4) receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP(4) versus the other EP prostanoid receptors.
制备了一系列7-[(5R)-取代的2-氧代-1-吡咯烷基]-庚酸，测定了它们的异构体纯度，并进行了药理学评价。对EP(4)受体具有亲和力的内酰胺表现出激动剂行为。内酰胺模板的较低侧链可以被取代，以提供对EP(4)的效力高且与其他EP前列腺素受体相比亲和力大于1000倍的配体（例如17、24、30、31和33）。
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