Agents that disrupt tubulin assembly are some of the most widely used cancer chemotherapeutics drugs. Inhibition of tubulin assembly can be achieved by targeting different sites of binding on tubulin, namely, the vinca binding site, the taxol binding site and the colchicine binding site (CBD). Currently CBD is of particular interest as there are no clinically approved agents available which bind to this site. In addition these agents provide the advantage of being effective against �-III resistant cancer cell lines. We have previously reported a series of 5-amino-6-chloro-2-methyl N4-substituted pyrimidines as potent anti-tubulin agents. These compounds circumvent �-III tubulin and Pgp- mediated drug resistance. These monocyclic compounds also have the advantage of being water soluble. To further explore the SAR of monocyclic pyrimidines as potential anti-tubulin agents additional analogs were designed and synthesized by interchanging the 5-amino and 6- chloro groups in the parent scaffold to determine its effect on biological activity. The design, synthesis and biological activities of these compounds will be presented.

Design, synthesis, and biological evaluation of 6-amino-5-chloro-2-methyl N<sup>4</sup>-substituted pyrimidine analogs as potential antitubulin agents

248th National Meeting (2014)

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Design, synthesis, and biological evaluation of 6-amino-5-chloro-2-methyl N4-substituted pyrimidine analogs as potential antitubulin agents

Design, synthesis, and biological evaluation of 6-amino-5-chloro-2-methyl N⁴-substituted pyrimidine analogs as potential antitubulin agents