Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Organic Chemistry

The present Thesis comprises six chapters and aims at the synthesis and evaluation of the anticancer activity of a number of tetrahydrobenzothieno [2,3-d] pyrimidines as well as tetrahydrobenzothieno [3,2-e][1,2,4] triazolo [4,3-a] pyrimidine derivatives. Chapter I is an introduction which consists of a brief literature survey on the recent approaches in the synthesis of thieno[2,3-d]pyrimidine derivatives and 1,2,4-triazolo[4,3-a]pyrimidines in addition to an account on their cytotoxic activity. Moreover, a brief account on matrix metalloproteinase inhibitors and their fundamental interactions with MMP binding sites is included. Chapter II presents the aim of the work together with illustration of the schemes carried out to obtain the new thieno [2,3-d]pyrimidine derivatives. Chapter III explains the theoretical discussion of the experimental work used for the synthesis of the newly synthesized compounds (schemes A-H) and spectroscopic confirmation of the intermediates and the target compounds. Scheme A is concerned with the preparation of the starting compound; ethyl 2- amino-4,5,6,7-tetrahydro[1] benzothiophene-3-carboxylate (I). Reaction of I with benzyl isothiocyanate yielded the key intermediate 3-benzyl-2-sulphanyl-5,6,7,8- tetrahydro-4-oxo(3H)-[1]benzothieno[2,3-d]pyrimidine (II). Alkylation of the 2- sulfanylthienopyrimidine II was carried out using different solvent/ base systems in order to obtain a series of S-alkylated derivatives VIa-d, VIIa-c and VIIIa-c which differ in the linker skeleton as well as the bioactive amine

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