Discovery and structural modification of novel inhibitors of PTP1B inspired by the ACT fragment of scleritodermin A

Yi Wei; Yue-Ting Chen; Lei Shi; Li-Xin Gao; Shen Liu; Yong-Mei Cui; Wei Zhang; Qiang Shen; Jia Li; Fa-Jun Nan

doi:10.1039/C1MD00153A

Discovery and structural modification of novel inhibitors of PTP1B inspired by the ACT fragment of scleritodermin A†

Yi Wei,^a Yue-Ting Chen,^a Lei Shi,^a Li-Xin Gao,^a Shen Liu,^a Yong-Mei Cui,^a Wei Zhang,^a Qiang Shen,^a Jia Li*^a and Fa-Jun Nan*^a

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* Corresponding authors

^a Chinese National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guoshoujing Road, Zhangjiang Hi-Tech Park, Shanghai, People's Republic of China
E-mail: fjnan@mail.shcnc.ac.cn, jli@mail.shcnc.ac.cn

Abstract

A series of compounds synthesized from a key intermediate in the total synthesis of Scleritodermin A containing a novel conjugated thiazole moiety, 2-(1-amino-2-p-hydroxyphenylethane)-4-(4-carboxy-2,4-dimethyl-2Z,4E-propadiene)-thiazole (ACT), were discovered to be potent inhibitors of protein tyrosine phosphatase 1B, with IC₅₀ values in the low micromolar range. Structure–activity relationships around the scaffold were investigated and some compounds exhibited more potent PTP1B inhibitory activity and improved specificities compared with the original hit.

MedChemComm

Discovery and structural modification of novel inhibitors of PTP1B inspired by the ACT fragment of scleritodermin A†

Abstract

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Discovery and structural modification of novel inhibitors of PTP1B inspired by the ACT fragment of scleritodermin A

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