3KC1

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

(2010) Bioorg Med Chem Lett 20: 1004-1007

• PubMed: 20045638 Search on PubMed
• DOI: https://doi.org/10.1016/j.bmcl.2009.12.056
• Primary Citation of Related Structures:  
  3KBZ, 3KC0, 3KC1


• PubMed 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 IC(50) 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 shape complementarity and to the hydrogen bonding network involving the side chain on the tricyclic scaffold.

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Organizational Affiliation: 

Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.