AI Article Synopsis
- New derivatives of (S)-isothiazolidinone (S)-IZD were developed to act as inhibitors of protein tyrosine phosphatase 1B (PTP1B) using a peptidomimetic approach.
- These inhibitors show strong competitive and reversible inhibition of PTP1B and have better absorption properties through Caco-2 cells.
- X-ray crystallography revealed the structural details of the inhibitors bonding with the PTP1B enzyme, highlighting specific interactions that contribute to their effectiveness.
Article Abstract
Benzothiazole benzimidazole (S)-isothiazolidinone ((S)-IZD) derivatives 5 were discovered through a peptidomimetic modification of the tripeptide (S)-IZD protein tyrosine phosphatase 1B (PTP1B) inhibitor 1. These derivatives are potent, competitive, and reversible inhibitors of PTP1B with improved caco-2 permeability. An X-ray co-crystal structure of inhibitor 5/PTP1B at 2.2A resolution demonstrated that the benzothiazole benzimidazole forms bi-dentate H-bonds to Asp48, and the benzothiazole interacts with the surface of the protein in a solvent exposed region towards the C-site. The design, synthesis, and SAR of this novel series of benzothiazole benzimidazole containing (S)-IZD inhibitors of PTP1B are presented herein.
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| http://dx.doi.org/10.1016/j.bmcl.2006.10.079 | DOI Listing |
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