REVIEW ARTICLE Synthesis and cytotoxic evaluation for some new 2,5-disubstituted pyrimidine derivatives for anticancer activity Onteddu Surendranatha Reddy • Ch. Venkata Suryanarayana • K. J. P. Narayana • V. Anuradha • B. Hari Babu Received: 11 June 2014 / Accepted: 28 September 2014 Ó Springer Science+Business Media New York 2014 Abstract An efficient synthetic approach for 2,5-disub- stituted pyrimidines has been reported. The desired 2,5- substituted pyrimidines were obtained by Suzuki coupling of 2-substituted benzyloxy-5-bromopyrimidines with vari- ous aryl boronic acids in the presence catalytic amount of PdCl 2 (PPh 3 ) 2 with 0.5 M aqueous Na 2 CO 3 in water at 80 °C. 2-Benzyloxy-5-bromopyrimidines were synthe- sized, in turn by the reaction of 2-chloro-5-bromopyrimi- dine with substituted benzyl alcohols in the presence of Cs 2 CO 3 in CH 3 CN:DMF (1:1). Some of the 2,5-disubsti- tuted pyrimidines have shown moderate in vitro cytotoxic activity against HeLa cell line. Keywords 2-Chloro-5-bromopyrimidine Á Cesium carbonate Á Green synthesis Á HeLa cell line Á PdCl 2 (PPh 3 ) 2 Introduction Nitrogen-containing heterocycles are widely found in nat- ure and are integral part of several biologically active compounds (Garcı ´a-Valverde and Torroba, 2005) (Fig. 1). Many biologically active compounds including nucleic acids, nucleotides, and corresponding nucleosides have pyrimidine as a core unit (Lagoja, 2005). It was reported that pyrimidines and their derivatives exhibited significant in vitro activity against DNA and RNA (Kappe, 1993). In addition, pyrimidine derivatives were found to possess inhibition properties against polio herpes viruses and as diuretics, antitumor agents, anti HIV agents, and for car- diovascular diseases (Kappe, 1993). Further, pyrimidines substituted with nitro group acted as novel allosteric enhancer of c-amino butyric acid receptor function (Ur- wyler et al., 2003). Moreover, heterocyclic compounds containing a CF 3 group exhibit wide range of biological activities (Berber et al., 2002; Jain et al., 2006). Boyd et al. (2001) utilized 2-methoxy bromopyrimidine for the syn- theses of 5-substituted pyrimidones as inhibitors for lipo- protein-associated phospholipase A. Recently, Xie et al. (2011) reported that 2,4,5-trisubstituted pyrimidines as a new class of tubulin polymerization inhibitors and 5-substituted-6-chloro uracils have been reported (Nencka et al., 2007) as efficient inhibitors of human thymidine phosphorylase which plays an important role in angiogen- esis. Conventional syntheses of pyrimidines are well doc- umented in the literature, those methods involve double condensation with elimination of water, alcohol, or hydro- gen halide between amino and carboxylic acid, acid chlo- ride or condensation of amino to CN groups or to polarized double bonds without elimination (Lagoja, 2005; Herrera et al., 2002). In view of aryl-substituted pyrimidines having great potential for anticancer activity, we have designed Electronic supplementary material The online version of this article (doi:10.1007/s00044-014-1276-6) contains supplementary material, which is available to authorized users. O. S. Reddy Á B. H. Babu (&) Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh, India e-mail: dr.b.haribabu@gmail.com Ch. V. Suryanarayana Á V. Anuradha Department of Chemistry, Vignan School of P.G. Studies, Guntur, Andhra Pradesh, India K. J. P. Narayana Department of Microbiology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh, India 123 Med Chem Res DOI 10.1007/s00044-014-1276-6 MEDICINAL CHEMISTR Y RESEARCH