Abstract
We present here the Energetic pharmacophore model representing complementary features of the 1,2,3,4-tetrahydropyrimidine for selective cyclooxygenase-2 (COX-2) inhibition. For the development of pharmacophore hypothesis, a total of 43 previously reported compounds were docked on active site of COX-2 enzyme. The generated pharmacophore features were ranked using energetic terms of Glide XP docking for 1,2,3,4-tetrahydropyrimidine scaffold to optimize its structure requirement for COX-2 inhibition. The thirty new 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine derivatives were synthesized and assessed for selective COX-2 inhibitory activity. Two compounds 4B1 and 4B11 were found to be potent and selective COX-2 inhibitors. The molecular docking studies revealed that the newly synthesized compounds can be docked into COX-2 binding site and also provide the molecular basis for their activity.
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Acknowledgments
The authors are thankful to University Grant Commission (UGC), New Delhi for financial assistance (No.F.37-145/2009). The authors thank the Head, Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004 (MS), India for providing the laboratory facility. Ms. Reecha Shah is a research assistant in ICMR funded project (No.53/6/2010-BMS).
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Lokwani, D., Shah, R., Mokale, S. et al. Development of energetic pharmacophore for the designing of 1,2,3,4-tetrahydropyrimidine derivatives as selective cyclooxygenase-2 inhibitors. J Comput Aided Mol Des 26, 267–277 (2012). https://doi.org/10.1007/s10822-011-9540-z
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DOI: https://doi.org/10.1007/s10822-011-9540-z