Synthesis and biological screening of diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates

Article abstract of DOI:10.24820/ark.5550190.p010.534

A three-step synthesis, involving condensation of bromomethyl aryl ketones with urea to afford 2- aminothiazoles, their chloroacetylation and subsequent solvent-free Arbuzov phosphonation has afforded a series of novel diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates 3a-3f in good overall yields; the 4- carboxythiazole analogue 3g was obtained by selective hydrolysis of the corresponding ethyl ester 3f. The phosphonate esters exhibited significant anti-cancer activity (nM - low μM IC₅₀ values) against SH-SY5Y cells and, in one case, 7.6 μM MIC90 anti-TB activity against the virulent M. tuberculosis H₃₇Rv strain; the chloroacetamido precursors all exhibited some antimalarial (PfLDH) activity, three with IC₅₀ values in the range 1.0 - 8.9 μM.