Synthesis and Cytotoxic Activity of Some Novel Thieno[2,3-d:4,5-d’]Dipyrimidine Derivatives

Elsherbiny Hamdy El-Sayed,Ahmed Ali Fadda

doi:10.17344/acsi.2018.4506

Abstract

Synthesis of some novel tricyclic compounds bearing thienodipyrimidine moiety by the reaction of ethyl 6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,2-d]pyrimidine-7-carboxylate (1) with different types of aromatic amines to give the corresponding carboxamide derivatives 2-11, which cyclized with triethyl orthoformate in acetic anhydride to afford thieno[2,3-d:4,5-d']dipyrimidine derivatives 12-15 is described. Similarly, thieno[2,3-d:4,5-d']dipyrimidine derivative 17 was also prepared via the reaction of carboxamide derivative 2 with chloroacetyl chloride in chloroform to give thieno[3,2-d]pyrimidine-7-carboxamide derivative 16, followed by a cyclization in boiling acetic anhydride. The structure of these compounds was confirmed on the basis of their spectral and analytical data such as IR, 1H-NMR, 13C-NMR spectroscopy and mass spectral data. The synthesized compounds were screened for their cytotoxic activity.

Highlights

The classes of tricyclic compounds bearing thienopyrimidine scaffolds have been the focus of great interest because of their pharmacological activities, such as antitumor,5–9 antiallergic, anti-inflammatory, analgesic, antifungal and antibacterial activities
Thienopyrimidines have become an important class of compounds in drug discovery programs and the medicinal chemistry
In continuation of our previous work on biologically active nitrogen and sulfur heterocycles,26–29 it was of interest to synthesize some novel thieno[2,3-d:4,5-d]dipyrimidine derivatives and evaluate these compounds for their cytotoxic activity

Summary

Introduction

Thienopyrimidines represent structural analogues for biogenic purines and potential nucleic acid antimetabolites. In particular, they are currently an important group of compounds that display anticancer activity, especially against solid tumors (e.g., breast and ovarian). On the other hand, the classes of tricyclic compounds bearing thienopyrimidine scaffolds have been the focus of great interest because of their pharmacological activities, such as antitumor, antiallergic, anti-inflammatory, analgesic, antifungal and antibacterial activities. thienopyrimidines have become an important class of compounds in drug discovery programs and the medicinal chemistry.21–25In continuation of our previous work on biologically active nitrogen and sulfur heterocycles, it was of interest to synthesize some novel thieno[2,3-d:4,5-d]dipyrimidine derivatives and evaluate these compounds for their cytotoxic activity. 2. Thienopyrimidines represent structural analogues for biogenic purines and potential nucleic acid antimetabolites.. Thienopyrimidines represent structural analogues for biogenic purines and potential nucleic acid antimetabolites.1 They are currently an important group of compounds that display anticancer activity, especially against solid tumors (e.g., breast and ovarian).. The classes of tricyclic compounds bearing thienopyrimidine scaffolds have been the focus of great interest because of their pharmacological activities, such as antitumor, antiallergic, anti-inflammatory, analgesic, antifungal and antibacterial activities.. Thienopyrimidines have become an important class of compounds in drug discovery programs and the medicinal chemistry.. In continuation of our previous work on biologically active nitrogen and sulfur heterocycles, it was of interest to synthesize some novel thieno[2,3-d:4,5-d]dipyrimidine derivatives and evaluate these compounds for their cytotoxic activity.

Objectives

Methods

Results

Conclusion