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

…, T Takakura, H Kotsubo, T Tanaka…

Index: Tsuchida, Keiichi; Chaki, Hisaaki; Takakura, Tadakazu; Kotsubo, Hironori; Tanaka, Tadashi; Aikawa, Yukihiko; Shiozawa, Shunichi; Hirono, Shuichi Journal of Medicinal Chemistry, 2006 , vol. 49, # 1 p. 80 - 91

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Citation Number: 29

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 ...