A novel class of AMPA receptor allosteric modulators. Part 1: design, synthesis, and SAR of 3-aryl-4-cyano-5-substituted-heteroaryl-2-carboxylic acid derivatives

  • Bioorg Med Chem Lett. 2006 Oct 1;16(19):5057-61. doi: 10.1016/j.bmcl.2006.07.035.
Maria-Carmen Fernandez  1 ,  Ana Castaño ,  Esteban Dominguez ,  Ana Escribano ,  Delu Jiang ,  Alma Jimenez ,  Eric Hong ,  William J Hornback ,  Eric S Nisenbaum ,  Nancy Rankl ,  Eric Tromiczak ,  Grant Vaught ,  Hamideh Zarrinmayeh ,  Dennis M Zimmerman
Affiliations
  • 1. Lilly S.A., Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain. [email protected]
PMID: 16879964 DOI: 10.1016/j.bmcl.2006.07.035
Abstract

The synthesis and initial SAR studies of novel, highly potent positive allosteric modulators of AMPA receptors based on 3-(4-tert-butylphenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid (6a) are described. SAR studies at the thioether moiety indicated that substitution at this position was mandatory and better potency was achieved with small groups.