Structure-based drug design of tricyclic 8H-indeno [1, 2-d][1, 3] thiazoles as potent FBPase inhibitors

T Tsukada, M Takahashi, T Takemoto, O Kanno…

Index: Tsukada, Tomoharu; Takahashi, Mizuki; Takemoto, Toshiyasu; Kanno, Osamu; Yamane, Takahiro; Kawamura, Sayako; Nishi, Takahide Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 3 p. 1004 - 1007

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Citation Number: 16

Abstract

With the goal of improving metabolic stability and further enhancing FBPase inhibitory activity, a series of tricyclic 8H-indeno [1, 2-d][1, 3] thiazoles was designed and synthesized with the aid of structure-based drug design. Extensive SAR studies led to the discovery of 19a with an IC50 value of 1nM against human FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due to the hydrophobic interaction arising from better ...