Facile Synthesis, Inhibition of VEGFR-2, Anticancer activity, Molecular Dynamics Simulation And Target Identification Of Some New Pyrano thiazine derivatives

A new series of)2-amino-4-(substituted)-4,10-dihydrobenzo[b]pyrano[2,3-e][1,4]thiazine-3-carbonitrile( 3(a, b) was synthesized by the reaction of 2-(substituted) malononitrile with 2H-benzo[b][1,4]thiazin-3(4H)-one as a key starting material,)2-amino-4-(substituted)-4,10-dihydrobenzo[b]pyrano[2,3-e][1,4]thiazine-3-carbonitrile( 3(a, b) reacted with some reagents, namely, formic acid, sulphuric acid, thiosemicarbazide, ethyl acetoacetate, triethyl orthoformate, carbon disulphide, diethylmalonate, malononitrile, phosphoryl chloride, and acetic anhydride to produce compounds 4(a,b), 5(a,b), 6(a,b), 8(a,b), 9(a,b), 10(a,b),11(a,b),14(a,b),15(a,b), and 18(a,b) some of newly synthesized compounds were studied and screened for their in vitro anticancer activity. Moreover, molecular dynamics simulation and target identification studies were conducted to support the findings.All the newly synthesized compounds were structurally confirmed by various modern analytical methods (IR, 1H NMR and MS).