In order to develop a better bioactive molecules with good efficacy, we synthesized a new series of Thiazolo [3,2-a] pyrimidine derivatives with good yield and studied their anthelmintic properties, structure- activity relationships (SARs). A new series of Thiazolo[3,2-a]pyrimidines have been synthesized through duff formylation, ‘One pot’ Biginelli reaction, cyclization followed by knoevenagel condensation and were characterized by IR, 1H NMR, 13C NMR, Mass spectra and elemental analysis. New molecules were screened for their in-vitro anthelmintic activity against Indian earthworm Pheretima posthuma and studied their physico-chemical properties. Effect of substitution at arylidene part on anthelmintic property was studied. Compounds 3j and 3s with electron withdrawing groups were found to be highly potent among the series and were also supported by ADME parameters.