Molecular modeling and synthesis of ZINC02765569 derivatives as protein tyrosine phosphatase 1B inhibitors: lead optimization study

Prashant Joshi, Girdhar Singh Deora, Vandana Rathore, Arun K. Rawat, A. K. Srivastava, Deepti Jain

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

This article describes design, synthesis, and molecular modeling studies of the ZINC02765569 derivatives as potent protein tyrosine phosphatase 1B (PTP1B) inhibitors, which was previously reported as a vHTS hit (ZINC02765569) by our laboratory. Ten compounds were synthesized and characterized by IR, MASS, and NMR followed by in vitro screening for PTP1B inhibition and glucose uptake in skeletal muscle L6 myotubes. The most potent compound 3j shows 66.4 % in vitro PTP1B inhibition and 39.6 % increase in glucose uptake. Glide was used to study the nature of interactions governing binding of designed molecules with active site of the PTP1B enzyme. 

Original languageEnglish
Pages (from-to)1618-1623
Number of pages6
JournalMedicinal Chemistry Research
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2013
Externally publishedYes

Keywords

  • Diabetes
  • Lead optimization study
  • Molecular modeling
  • PTP1B inhibitors
  • ZINC02765569 derivatives

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