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Medicinal Chemistry Research

, Volume 22, Issue 7, pp 3478–3484 | Cite as

Pharmacophore modeling and 3D QSAR analysis of isothiazolidinedione derivatives as PTP1B inhibitors

  • Girdhar Singh Deora
  • Prashant Joshi
  • Vandana Rathore
  • K. Lalith Kumar
  • Renu Ohlyan
  • Ajit Kandale
Original Research

Abstract

The article describes the development of a robust pharmacophore model and investigation of structure activity relationship analysis of 56 isothiazolidinedione derivatives reported as PTP1B inhibitors. A six-point pharmacophore model consisting of four aromatic rings (R), one hydrogen bond donor (D) and one hydrogen bond acceptor (A) with discrete geometries as pharmacophoric features was developed and the generated pharmacophore model was used to derive a predictive 3D QSAR model for the studied dataset. The obtained 3D QSAR model has an excellent correlation coefficient value (r 2 = 0.98) along with good statistical significance as shown by a high Fisher ratio (F = 428.60). The model also exhibits good predictive power confirmed by the high value of cross-validated correlation coefficient (q 2 = 0.62). The QSAR model suggests that hydrophobic aromatic character is crucial for the PTP1B inhibitory activity at the R-15 site.

Keywords

Isothiazolidinedione derivatives PTP1B inhibitors Pharmacophore modeling 3D QSAR PHASE 

Supplementary material

44_2012_349_MOESM1_ESM.doc (604 kb)
Supplementary material 1 (DOC 604 kb)

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Girdhar Singh Deora
    • 1
    • 2
  • Prashant Joshi
    • 1
  • Vandana Rathore
    • 3
  • K. Lalith Kumar
    • 2
  • Renu Ohlyan
    • 4
  • Ajit Kandale
    • 2
  1. 1.School of Pharmaceutical SciencesRajiv Gandhi Prodyogiki VishwavidyalayaBhopalIndia
  2. 2.Institute of Life SciencesUniversity of Hyderabad CampusHyderabadIndia
  3. 3.B. N. Institute of Pharmaceutical SciencesUdaipurIndia
  4. 4.M.M. College of PharmacyAmbalaIndia

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