Shepherd Timothy A, Aikins James A, Bleakman David, Cantrell Buddy E, Rearick John P, Simon Richard L, Smith Edward C R, Stephenson Gregory A, Zimmerman Dennis M, Mandelzys Allan, Jarvie Keith R, Ho Ken, Deverill Michelle, Kamboj Rajender K
NPS Allelix Corporation, 6850 Goreway Drive, Mississaugua, Ontario L4V 1V7, Canada.
J Med Chem. 2002 May 9;45(10):2101-11. doi: 10.1021/jm0105474.
2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) potentiators are ligands that act as positive allosteric modulators at the AMPA receptors. We recently disclosed a novel series of 2-arylpropylsulfonamides that were potent potentiators of responses mediated through AMPA receptors. To further define the structural requirements for activity in this series, new ring-constrained analogues were prepared and a new stereocenter was introduced. The potentiating activity was highly dependent on the stereochemistry at the 2-position of the disubstituted cyclopentane and was independent of the relative stereochemistry at the 1-position. Compound (R,R)-10 represents a potent, novel potentiator of iGluR4 flip receptors (EC(50) = 22.6 nM).
2-氨基-3-(3-羟基-5-甲基异恶唑-4-基)丙酸（AMPA）增强剂是在AMPA受体上作为正变构调节剂起作用的配体。我们最近公开了一系列新型的2-芳基丙基磺酰胺，它们是通过AMPA受体介导的反应的强效增强剂。为了进一步确定该系列中活性的结构要求，制备了新的环约束类似物并引入了新的立体中心。增强活性高度依赖于二取代环戊烷2-位的立体化学，且与1-位的相对立体化学无关。化合物(R,R)-10是一种强效的新型离子型谷氨酸受体4翻转受体增强剂（半数有效浓度（EC(50)）=22.6 nM）。
