Dineshkumar Manvar - Synthesis, screening for antitubercular activity and 3D-QSAR studies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxamides.

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      Publication Details (including relevant citation   information):

      European Journal of Medicinal Chemistry, 2008, 43 (10), 2103-2115

      Abstract:

      Multi-drug resistance to commonly used antitubercular drugs has   propelled the development of new structural classes of   antitubercular agents. This paper reports the synthesis,   evaluation and 3D-QSAR analysis of a set of substituted   N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamides   as antitubercular agents. Substituted acetoacetanilides were   reacted with various aromatic aldehydes and urea which yielded   the tetrahydropyrimidine derivatives with a phenyl carbamoyl   group at C5 position, and with various substitutions on the   4-phenyl and the N-phenyl aromatic rings. All compounds were   screened for antitubercular activity against Mycobacterium   tuberculosis H37Rv strain. The QSAR models were generated on a   training set of 23 molecules. The molecules were aligned using   the atom-fit and field-fit techniques. The CoMFA and CoMSIA   models generated on the molecules aligned by the atom-fit method   show a correlation coefficient (r2) of 0.98 and 0.95 with   cross-validated r2(q2) of 0.68 and 0.58, respectively. The   3D-QSAR models were externally validated against a test set of 7   molecules for which the predictive r2 (r(pred)2) is recorded as   0.41 and 0.32 for the CoMFA and CoMSIA models, respectively. The   CoMFA and CoMSIA contours helped to design some new molecules   with improved activity.

      Address (URL): http://www.sciencedirect.com/science/article/pii/S0223523407003248