Jenson Verghese - CoMFA Study on Thiazolidine-2,4-diones for their Antihyperglycemic Activity

Version 1

      Publication Details (including relevant citation   information):

      Letters in Drug Design & Discovery, 2008, 5, 79-87


      The present CoMFA study on thiazolidine-2,4-diones attempts to   quantitatively describe the structural features
      of the compounds for high PPAR- agonistic action. A set of 50   compounds was used for the analysis. A training set and a
      test set were designed consisting of 39 and 11 compounds,   respectively. All the molecules were modeled and energy
      minimized using SYBYL 6.7 software. The molecules were aligned   using the most active analog as the template by field
      fit method. PLS (partial least square) analysis was performed on   the training set and statistical parameters like q2, r2, F
      value and P value were calculated. A final model was generated by   excluding four outliers from the training set. Cross
      Validation was done by leave one out method. The developed CoMFA   model showed a good external as well as internal
      predictivity in most of the compounds with low residual values.   The q2 value of the developed model was 0.549 and r2
      value was 0.976. Contour plots generated from the steric and   electrostatic contributions of this model were used to derive
      structure-activity relationships and to design a hypothetical   molecular structure, which can be used as a lead for design
      and syntheses of newer molecules.

      Address (URL): .SGM