Document Report Card

ID: ALA1135411

Journal: J Med Chem

Title: 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.

Authors: Shepherd TA, Aikins JA, Bleakman D, Cantrell BE, Rearick JP, Simon RL, Smith EC, Stephenson GA, Zimmerman DM, Mandelzys A, Jarvie KR, Ho K, Deverill M, Kamboj RK.

Abstract: 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).

CiteXplore: 11985477

DOI: 10.1021/jm0105474