SYNTHESIS AND CHARACTERIZATION OF (S)-3-(5- FLUOROPYRIDIN-2-YL)-5-(PIPERIDIN-3-YL)-L,2,4-OXADIAZOLE DERIVATIVES AND THEIR SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITOR ACTIVITY

摘要

The present invention relates to development of novel (S)-3 -(5 -fluoropyridin-2-yl)-5 -(piperidin- 3-yl)- 1,2,4-oxadiazole derivatives. It particularly relates to the development of novel compounds of (S)-3 -(5 -fluoropyridin-2-yl)-5 -(piperidin-3 -yl)- 1,2,4-oxadiazole derivatives as inhibitors of Secretory Phospholipase A2 (sPLA2). It also relates synthetic process for preparation of novel compounds of (S)-3-(5-fluoropyridin-2-yl)-5-(piperidin-3-yl)-1,2,4-oxadiazole derivatives as inhibitors of Secretory Phospholipase A2 (sPLA2). It further relates to the development of composition with novel compounds of (S)-3-(5-fluoropyridin-2-yl)-5-(piperidin-3-yl)-1, 2,4- oxadiazole derivatives for inhibition of Secretory Phospholipase A2 (sPLA2). The final compounds were characterized by 1H and 13C-NMR, IR, LC-MS and Elemental analysis. In vitro inhibitory effect of series of 7(a-s) [Formula I] on VRV-PL-8a were assessed for PLA2 inhibition studies. The tested compounds 7(a-s) [Formula I] inhibited sPLA2 in dose-dependent manner with an IC50 value ranging from 9.2 to 82μΜ which are computed and analyzed using sigmoidal 4PL curve fit.