Bioorganic & Medicinal Chemistry Letters 2007-08-15

Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors.

Mankil Jung, Yongnam Lee, Moonsoo Park, Hanjo Kim, Heekyeong Kim, Eunyoung Lim, Jungae Tak, Minjoo Sim, Dongeun Lee, Namsoo Park, Won Keun Oh, Kyu Yeon Hur, Eun Seok Kang, Hyun-Chul Lee

Index: Bioorg. Med. Chem. Lett. 17 , 4481-6, (2007)

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Abstract

Dihydroxy stilbene derivatives were designed based on lithospermic acid B and were prepared from 4-(chloromethyl)benzoic acid. The inhibitory activities of the novel compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated. 3,4-Dihydroxy stilbene carbonyl compounds (7, 11b, 27b) inhibited PTP1B with IC50 values comparable to molybdate, while the conjugation-extended compound (15b) showed inhibition 3-fold better than preclinical RK682. The introduction of electron withdrawing groups or amides into the second phenyl ring, or extension of the conjugation into the stilbene molecule may increase stability of the generated radicals.