Dineshkumar Manvar - Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines.

Version 1

      Publication Details (including relevant citation   information):

      Molecular Diversity, 2009,    14 (2), 285-305,

      Abstract:

      In continuation of our research program on new antitubercular   agents, this article is a report of the synthesis of 97 various   symmetrical, unsymmetrical, and N-substituted   1,4-dihydropyridines. The synthesized molecules were tested for   their activity against M. tuberculosis H 37Rv strain with   rifampin as the standard drug. The percentage inhibition was   found in the range 3–93%. In an effort to understand the   relationship between structure and activity, 3D-QSAR studies were   also carried out on a subset that is representative of the   molecules synthesized. For the generation of the QSAR models, a   training set of 35 diverse molecules representing the synthesized   molecules was utilized. The molecules were aligned using the   atom-fit technique. The CoMFA and CoMSIA models generated on the   molecules aligned by the atom-fit method show a correlation   coefficient (r 2) of 0.98 and 0.95 with cross-validated r 2(q 2)   of 0.56 and 0.62, respectively. The 3D-QSAR models were   externally validated against a test set of 19 molecules (aligned   previously with the training set) for which the predictive   r2(r2pred) is recorded as 0.74 and 0.69 for the CoMFA and CoMSIA   models, respectively. The models were checked for chance   correlation through y-scrambling. The QSAR models revealed the   importance of the conformational flexibility of the substituents   in antitubercular activity.

      Address (URL): http://