Document Report Card

ID: ALA1148596

Journal: J Med Chem

Title: Discovery of nonpeptidic small-molecule AP-1 inhibitors: lead hopping based on a three-dimensional pharmacophore model.

Authors: Tsuchida K, Chaki H, Takakura T, Kotsubo H, Tanaka T, Aikawa Y, Shiozawa S, Hirono S.

Abstract: We designed and synthesized small-molecule activator protein-1 (AP-1) inhibitors based on a three-dimensional (3D) pharmacophore model that we had previously derived from a cyclic decapeptide exhibiting AP-1 inhibitory activity. New AP-1 inhibitors with a 1-thia-4-azaspiro[4.5]decane or a benzophenone scaffold, which inhibit the DNA-binding and transactivation activities of AP-1, were discovered using a "lead hopping" procedure. An additional investigation of the benzophenone analogues confirmed the reliability of the pharmacophore model, its utility to discover AP-1 inhibitors, and the potency of the benzophenone derivatives as a lead series.

CiteXplore: 16392794

DOI: 10.1021/jm050550d