Synthesis of a FTO inhibitor with anticonvulsant activity

具有抗惊厥活性的FTO抑制剂的合成

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作者:Guanqun Zheng, Thomas Cox, Leah Tribbey, Gloria Z Wang, Paulina Iacoban, Matthew E Booher, Gregory J Gabriel, Lu Zhou, Nancy Bae, Joie Rowles, Chuan He, Mark J Olsen

Abstract

We describe the rationale for and the synthesis of a new class of compounds utilizing a modular approach that are designed to mimic ascorbic acid and to inhibit 2-oxoglutarate-dependent hydroxylases. Preliminary characterization of one of these compounds indicates in vivo anticonvulsant activity (6 Hz mouse model) at nontoxic doses, inhibition of the 2-oxoglutarate-dependent hydroxylase FTO, and expected increase in cellular N(6)-methyladenosine. This compound is also able to modulate various microRNA, an interesting result in light of the recent view that modulation of microRNAs may be useful for the treatment of CNS disease.

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