Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.

M Sodeoka, R Sampe, S Kojima, Y Baba, T Usui, K Ueda, H Osada

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai 980-8577, Japan. sodeoka@tagen.tohoku.ac.jp

Journal of medicinal chemistry 2001 Sep 27

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Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibitors in which 3-acyltetronic acid is used as a "core" phosphate mimic. A series of novel tetronic acid derivatives were synthesized and evaluated as inhibitors of the dual-specificity protein phosphatases VHR and cdc25B. Several compounds are found to be potent inhibitors of cdc25B, which is a key enzyme for cell-cycle progression. The promising results described herein strongly indicated that this tetronic acid library is potent as a library focused on the PTP/DSP-selective inhibitor.

Citation

M Sodeoka, R Sampe, S Kojima, Y Baba, T Usui, K Ueda, H Osada. Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition. Journal of medicinal chemistry. 2001 Sep 27;44(20):3216-22