ABSTRACT Pyrimidine-5-sulfonamides are new organic compounds of wide spectrum activity. A new trend is to incorporate a salicylate moiety in an attempt to enhance a thrombolytic activity. We started this strategy using 2-thiouracil 1 as a blocking unit by its ability to be chlorosulfonated at 5th position by refluxing with chlorosulfonic acid giving sulfonyl derivative 2 which was condensed with three common aromatic amines namingmethyl-4- aminosalicylate, methyl-3-aminobenzoate and methyl-4-aminobenzoate respectively yielding sulfonamide derivatives 3a-c. Moreover, 3a-c derivatives were reacted with chloroacetic acid-producing thiazolopyrimidines 4a-c,which in turn were reacted with pnitrobenzaldehyde giving arylidine derivatives 5a-c. Also compounds 3a-c were cyclocondensed with anthranilic acid yielding pyrimidoquinazoline derivatives 6a-c. They also were condensed with ethanolamine forming imidazopyrmidine derivatives 7a-c. All the newly synthesized compounds were subjected for thrombolytic evaluation and some of them showed promising activity especially those bearing methyl salicylate moiety as compared to ticlopidine and clopidogrel. We performed different modifications in the thienopyridine chemical structure of ticlopidine and clopidogrel to conclude that the presence of second nitrogen atom in the pyridine ring (yielding pyrimidine moiety) and the presence of the other cycle instead of thienyl ring would lead to enhanced the thrombolytic effect which was maximized by incorporation of a methyl salicylate moiety. We concluded that 4a, 6a, 8a, 7a, 3a, compounds have more potent than both clopidogrel and ticlopidine respectively. They certainly deserve further studying in the future.