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ABSTRACT:
We have synthesized various substituted thieno(2,3-d)pyrimidines, first by synthesizing ethyl 2-aminothiophene-3- carboxylate (3), by treatment of diethane with ethyl cynoacetate in presence of triethylamine, acetic acid and DMF. Further, the intermediate Ethyl 2-(ethoxycarbonyl)thiophene-3-carboxylate (5) was prepared by compound (3) refluxed with ethyl chloroformate. The key intermediate 3-(3-chloro-4-fluorophenyl) thieno [2, 3-d]pyrimidine-2, 4(1H, 3H)-dione (7) was prepared by cyclisation of compound (5) with 3-chloro-4-fluoro aniline. The nucleophilic substitution of compound 3-(3-chloro-4-fluorophenyl) thieno [2, 3-d]pyrimidine-2, 4(1 H, 3 H)-dione (7) with various aromatic amines(8a-m), aminophenol(8n) gives substituted thienopyrimidines(8a-n). The synthesized new compounds were characterized by MP, TLC, IR and NMR spectra.
KEYWORDS: Thienopyrimidine
INTRODUCTION:
The known approaches to the synthesis of thienopyrimidines can be divided into two main groups: the construction of the pyrimidine ring by intramolecular cyclization of thiophene derivatives and the thiophene ring closure in pyrimidine derivatives.
Synthetic approaches to the construction of thienopyrimidines are sufficiently well developed. Three possible types of annelation of thiophene to the pyrimidine ring and correspondingly, Three isomeric thieno pyrimidines are known: thieno[2,3-d]pyrimidine, thieno[3,2-d]pyrimidine, and thieno[3,4-d]pyrimidine.
Condensed thienopyrimidines exhibit interesting biological activity like antibacterial1-6, anticancer 7-10, aldose reductase inhibitor 11, 12, antiviral activity 13-14, anti-inflammatory and analgesic 15-16, anticonvulsant 17, antipsychotic18, DHFR inhibitory19, VEGFR-2 kinase inhibitors 20, tyrosine kinase inhibitors21, adenosine receptor binding properties22
In continuation with our past research on synthesizing a novel class of thienopyrimidines and testing them for appropriate pharmacological activity. Here in, we are presenting synthesis of substituted thieno(2,3-d)pyrimidines 8(a-n) and their antibacterial activities.
Bacteria that resist the effects of the most powerful antibiotics are posing a great challenge to the field of medicines. Thus scientists are working to find new ways to defeat bacteria, which are increasingly resistant to the antibiotics already available.
To achieve the above mentioned target, scientists have utilized the concept of bioisosterism. It has been defined as group of molecules, which have chemical and physical similarities producing broadly similar biological properties. It is now known that many heterocycles, when appropriately substituted exhibits bioisosterism. Thienopyrimidines occupy a special position among these as these are the structural analogs of biogenic purines. It has been well established, that thienopyrimidines are bioisosteres of quinazolines.
EXPERIMENTAL:
Melting points were determined by Thiel's melting point tube( capillary tube method). I.R. were recorded on Shimadzu 8700...