Synthesis of 4-Azaindole-morpholine-1,3,4-oxadiazole Conjugates as Epidermal Growth Factor Receptor Inhibitors

Herein, we synthesized some new 4-azaindole-morpholine-1,3,4-oxadiazole conjugates (11 a-n) and evaluated for their in vitro anticancer potency towards three human cancer cell lines namely MCF-7, A549 and HepG2 using MTT assay. Among all, compounds (1-((5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridin-3-yl) (morpholino) methanone (11 d), 4-(5-((3-(morpholine-4-carbonyl)-1H-pyrrolo[3,2-b]pyridin-1-yl)methyl)-1,3,4-oxadiazol-2-yl) benzonitrile (11 f) and (1-((5-(4-chloro-3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)(morpholino) methanone (11 k) displayed greater in vitro activity against all the cell lines than the erlotinib with IC50 values ranging from 1.12 to 14.15 mu M. The active compounds 11 d, 11 f and 11 k were also screened for their inhibiting power of tyrosine kinase EGFR and results revealed that the compounds 11 d and 11 f exhibited more inhibition than the standard erlotinib. Further, docking studies of compounds 11 d, 11 f and 11 k on EGFR revealed that compound 11 d had highest binding energy (-10.37 kcal/mol). Finally, compounds 11 d and 11 f followed the rules of Lipinski, Ghose, Veber, Egan rule and Muegge rules without any deviation.