Effects of five-membered ring conformation on bioreceptor recognition: identification of 3R-amino-1-hydroxy-4R-methylpyrrolidin-2-one (L-687,414) as a potent glycine …

…, BJ Williams, R Baker, T Ladduwahetty…

Index: Leeson; Williams; Baker; Ladduwahetty; Moore; Rowley Journal of the Chemical Society - Series Chemical Communications, 1990 , # 22 p. 1578 - 1580

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Citation Number: 19

Abstract

Syntheses of the 4-methyl (2 and 3) and [3.2. 1] bicyclo (4 and 5) analogues of the glycine/N- methyl-D-aspartate (NMDA) antagonist 3-amino-1-hydroxypyrrolidin-2-one (HA-966, 1) provide evidence that glycine receptor recogntion requires the energetically less favoured 3- pseudoaxial conformation of the pyrrolidone ring, resulting in a 5–10 fold improvement in activity with the 3R-amino, 4R-methyl derivative (2a, L-687,414).