Design and Synthesis of a Novel Series of 1,2-Disubstituted Cyclopentanes as Small, Potent Potentiators of 2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic Acid (AMPA) Receptors
2002; American Chemical Society; Volume: 45; Issue: 10 Linguagem: Inglês
10.1021/jm0105474
ISSN1520-4804
AutoresTimothy A. Shepherd, James Aikins, David Bleakman, Buddy E. Cantrell, John P. Rearick, Richard L. Simon, Edward C. Smith, Gregory A. Stephenson, Dennis M. Zimmerman, Allan Mandelzys, Keith R. Jarvie, Ken H. Ho, Michelle Deverill, Rajender K. Kamboj,
Tópico(s)Bioactive Compounds and Antitumor Agents
Resumo2-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).
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