Structure‐Based Optimization of Protein Tyrosine Phosphatase‐1 B Inhibitors: Capturing Interactions with Arginine 24
2008; Wiley; Volume: 3; Issue: 10 Linguagem: Inglês
10.1002/cmdc.200800188
ISSN1860-7187
AutoresZhao‐Kui Wan, Jinbo Lee, Rajeev Hotchandani, Alessandro Moretto, Eva Binnun, Douglas Wilson, Steve Kirincich, Bruce Follows, Manus Ipek, Weixin Xu, Diane Joseph‐McCarthy, Yan‐Ling Zhang, May Tam, David V. Erbe, James F. Tobin, Wei Li, S. Y. K. TAM, Tarek S. Mansour, Junjun Wu,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoFurther optimization efforts on the previously disclosed PTP-1B inhibitor 1 a led to the discovery of a new series of potent compounds, for example derivative 33, which targeted the second phosphotyrosine binding pocket near the catalytic site. In the new series, the N-sulfonylpiperidine group of 1 a was replaced with a smaller substituent, capable of forming a new hydrogen bond interaction with arginine 24. The series reported here maintains the binding mode of 1 a and has the added advantages of a lower molecular weight, smaller polar surface area, and fewer rotatable bonds.
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