Journal of Computer-Aided Molecular Design

, Volume 26, Issue 3, pp 267–277

Development of energetic pharmacophore for the designing of 1,2,3,4-tetrahydropyrimidine derivatives as selective cyclooxygenase-2 inhibitors

  • Deepak Lokwani
  • Reecha Shah
  • Santosh Mokale
  • Padma Shastry
  • Devanand Shinde
Article

DOI: 10.1007/s10822-011-9540-z

Cite this article as:
Lokwani, D., Shah, R., Mokale, S. et al. J Comput Aided Mol Des (2012) 26: 267. doi:10.1007/s10822-011-9540-z

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.

Keywords

E-pharmacophoreDocking1,2,3,4-tetrahydropyrimidineCOX-2Glide XP

Supplementary material

10822_2011_9540_MOESM1_ESM.doc (592 kb)
Supporting Materials (DOC 592 kb)

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Deepak Lokwani
    • 1
  • Reecha Shah
    • 2
  • Santosh Mokale
    • 3
  • Padma Shastry
    • 2
  • Devanand Shinde
    • 1
  1. 1.Department of Chemical TechnologyDr. Babasaheb Ambedkar Marathwada UniversityAurangabadIndia
  2. 2.National Centre for Cell Science (NCCS)Ganeshkhind, PuneIndia
  3. 3.Y.B. Chavan College of PharmacyAurangabadIndia