Thieno[2,3-d]pyrimidines in the Synthesis of New Fused Heterocyclic Compounds of Prospective Antitumor and Antioxidant Agents (Part II)

Diethyl azodicarboxylate and 3,4,5,6-tetrachloro-1,2-benzoquinone react with cyclopentano- and cycloheptano-fused thienopyrimidines to form the oxidative dimer of the starting material via S-S bond formation. Reaction of two equivalents of 2,2'-(cyclohexa-2',5'-diene-1,4-diylidene)dimalononitrile with thienopyrimidines afforded 3-(4',4'-dicyanomethylene-cycloalka[a]-2,5-dienyl)-4-oxo-6,7,8,9-tetrahydro-5H-cyclo-hepta[4,5]-[1,3]thiazolo[3,2-a]-thieno[2,3-d]pyrimidin-2-ylidene-2-dicarbonitriles. The thioenopyrimidines react with 2-[1,3-dioxo-1H-inden-2(3H)-ylidene]malononitrile to produce 1,3,5'-trioxo-1,3,3',5'-tetrahydrospiro-(indene-2,2'-thiazolo[2,3-b]-cycloalkyl[b]-thieno[2,3-d]pyrimidine)-3'-carbonitriles. However, the reaction of thienopyrimidines with 2,3-dicyano-1,4-naphthoquinone proceeded to afford the fused cycloalkyl-thieno form of naphtho[1,3] thiazolo[3,2-a]thieno[2,3-d]pyrimidine-6.7,12-triones. Reaction of 2-hydrazino-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidine-4(1H)-one with dimethyl acetylenedicarboxylate and ethyl propiolate, respectively, afforded cyclohexano-fused (Z)-dimethyl 2 [(E)-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-2(1H)-ylidene)hydrazono]succinate and thieno-pyrimidinotriazine. Both oxidative dimers of thienopyrimidines showed high inhibition of Hep-G2 cell growth compared with the growth of untreated control cells. Moreover, the cycloheptano-fused thiazinothienopyrimidine indicates a promising specific antitumor agent against Hep-G2 cells because its IC50 is < 20 mu M.