Novel 4‐Heteroaryl‐antipyrines: Synthesis, Molecular Docking, and Evaluation as Potential Anti‐breast Cancer Agents

Abstract

Reaction of 1‐[4‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3 H ‐pyrazol‐4‐yl)‐2‐phenylsulfonyl‐1‐ethanone ( 1 ) with phenyl isothiocyanate afforded the 4‐(3‐mercapto‐3‐(phenylamino)‐2‐(phenylsulfonyl)acryloyl)‐1,5‐dimethyl‐2‐phenyl‐1 H ‐pyrazol‐3(2 H )‐one ( 2 ). Treatment of compound 2 with hydrazonoyl chlorides 3a – h afforded the corresponding1,3,4‐thiadiazole derivatives 5a – h . Cyclocondensation reaction of compound 2 with the appropriate α‐halo‐compounds 6 , 8 , 10 , 12a , b or 14 (ethyl 2‐chloroacetate, chloroacetonitrile, 1‐chloropropan‐2‐one, 2‐bromo‐1‐phenylethanone, 2‐bromo‐1‐ p ‐tolylethanone, and 2‐bromoacetyl‐3 H ‐benzo [f]chromen‐3‐one) afforded the 1,3‐thiazole derivatives 7 , 9 , 11 , 13a , b , and 15 , respectively. Coupling of the ketosulphone 1 with the appropriate diazotized 4 H ‐1,2,4‐triazol‐3‐amine 16 and 2‐aminobenzimidazole 19 afforded triazolo[5,1‐c][1, 2, 4]triazine 18 and benzo[4,5]imidazo[2,1‐c][1, 2, 4]triazine 21 , respectively. The structures of the synthesized compounds were confirmed on the basis of their elemental analysis and spectral data and evaluated as potential anti‐breast cancer agents. Moreover, the computational studies using MOE 2014.09 software are confirming the results in biological activity.