Synthesis and Biological Evaluation of Some New Pyrimidines

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General Papers

ARKIVOC 2008 (xi) 131-141

Synthesis and biological evaluation of some new pyrimidines via a novel chalcone series Amit R.Trivedi, Dipti K. Dodiya, Naresh R. Ravat, and Viresh H. Shah* Department of Chemistry, Saurashtra University, Rajkot (Gujarat), India, Pin-360005 E-mail:

Abstract In the present investigation ethyl 2-(4-carboxyphenylazo)acetoacetate 1 on condensation with various aromatic aldehydes in ethanolic NaOH solution yielded the corresponding chalcones 2a-j. These chalcones were further reacted with urea in the presence of base in ethanol, which led to the formation of pyrimidine derivatives 3a-j. The newly synthesized heterocyles were characterized on the basis of their chemical properties and spectroscopic data. All newly synthesized compounds were evaluated for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv. Keywords: Pyrimidine, antimycobacterial, Mycobacterium tuberculosis

Tuberculosis (TB) is by far the most frequently encountered mycobacterial disease in the world.1 Although its incidence has diminished significantly in the industrially more developed countries; it remains a major public health problem in most of the developing nations. Tuberculosis is still the single largest infection having a high mortality rate and 0.1 to 0.3 percent of the population become infected each year in the developed countries. This year, 2 million people may develop the disease and 30 million may die worldwide (as per a WHO report). It is commonly known that Mycobacterium tuberculosis has developed resistance to the majority of the existing drugs. However, powerful new anti-TB drugs with new mechanisms of action have not been developed in the last forty years. In the developing countries, the annual infection rate is 20–50 times greater than in the developed countries and its high level shows little or no downward trend. It is expected that development of new effective anti-TB drugs will bring various outcomes viz: shortening the total duration of therapy, reducing the total expenditure and treatment of multiple drug resistant tuberculosis (MDR-TB) by single dosage regiment.2,3 In pursuit of achieving this goal, our research efforts are focused on the development of novel structural moieties having antimycobacterial properties.4,5 Chalcones have various biological activities such as cytotoxic,5

ISSN 1551-7012

Page 131



General Papers

ARKIVOC 2008 (xi) 131-141

antimalarial,6 antioxidant,7 tyrosinase Inhibitory,8 anti-inflammatory,9 cancer chemopreventive9 and antibacterial.10 Several pyrimidine derivatives have wide varieties of usages and its nucleus is also present in vitamin B2 and folic acid. Pyrimidine heterocycles possessing hydroxyl group has a unique place in medicinal chemistry,11 and also plays a vital role in biological processes12, 13 as well as synthetic drugs.14 Pyrimidines are associated with various therapeutic activities e.g., anti-HIV,15 anti-tubercular,16 antitumor,17 antineoplastic,18 anti-inflammatory,19 diuretic,20 antimalaria,21 cardiovascular.22 To the best of our knowledge, there has been no previous reports of analogous pyrimidines and parent chalcones as antituberculosis agents. However, there are numerous examples of nitrogen containing heterocycles being used to treat TB, for example Clofazimine, Isoniazid and Pyrazinamide. These compounds provide structural precedence that our chalcone and pyrimidine analogues may lead to the generation of novel anti-TB therapeutics. Herein the synthesis and in vitro antimycobacterial activity of novel chalcone and pyrimidine derivatives are described.

Results and Discussion
Chemistry The synthesis of chalcone and pyrimidine derivatives was performed following the steps shown in Scheme-1. In the initial step, chalcones (2a-j) were synthesized by condensing 2-(4carboxyphenylazo)acetoacetate23 1 with appropriate arometic aldehydes in...
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