Development of energetic pharmacophore for the designing of 1,2,3,4-tetrahydropyrimidine derivatives as selective cyclooxygenase-2 inhibitors.
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.
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, MS 431004, India.
Deepak
D
Lokwani
Reecha
R
Shah
Santosh
S
Mokale
Padma
P
Shastry
Devanand
D
Shinde
D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D011743:Pyrimidines