Synthesis and antiinflammatory activity of novel 2,5-disubstituted thiophene derivatives

New series of 2,5-disubstituted thiophenes were synthesized. Thiosemicarbazones 1a-b were reacted with various reagents, such as diethyl-2-bromomalonate, ethyl-2-chloroacetoacetate, thioglycolic acid, 4- ubstituted phenacyl bromides, and acetic anhydride, to afford heterocyclic substituted thiophene deriva- ives 2a-b, 3a-b, 4a-b, 5a-b, 6a-b,and 7a-b, respectively. Moreover, cyclization of the key intermediate 1b with chloroacetic acid yielded thiazolidine 9, which on reaction with appropriate aromatic aldehydes af- orded the corresponding arylidene derivatives 10a-f. Finally, reaction of N -arylidene cyanoacetohydrazide 11 with sulfur and phenylisothiocyanate yielded thiazoline derivative 12, which on treatment with triethy- orthoformate and acetic anhydride afforded thiazolo[4,5-d]pyrimidinone derivative 13. Some of the newly ynthesized compounds showed promising antiinflammatory activity.