Intrinsic and acquired multidrug resistance (MDR) is a limitation in the clinical efficacy of many anticancer drugs including those that target microtubules. We previously reported water soluble antitubulins N-(4'-methoxyphenyl)-N, 2, 6-trimethyl cyclopenta[d]pyrimidin-4-amine 1  (IC50=17 nM) and N-(4'-methoxyphenyl)-N, 2-dimethyl pyrrolo[2,3-d]pyrimidin-4-amine 2  (IC50=183 nM) as inhibitors of the proliferation of human cancer cells (MDA-MB-435) in culture, as well as parental and Pgp expressing SKOV-3 cell lines (IC50 38.6 nM and 278 nM respectively). In this report we present the novel synthesis and biological activities of the 5, 6-dihydropyrrolo[2,3-d]pyrimidine scaffold as cytotoxic agents. This scaffold possesses both the flexibility of the fused cyclopenta ring in 1  and the hydrogen bonding ability of the fused pyrrole ring in 2  . The novel synthesis and cytotoxic activities of methyl and desmethyl substituted 4-(4'-methoxyphenylamine)-5, 6-dihydropyrrolo[2,3-d]pyrimidines will be presented and discussed.

Novel methodology for the synthesis of methyl substituted 4-(4'-methoxyphenylamine)-5, 6-dihydropyrrolo[2,3-<i>d</i>]pyrimidines as water-soluble microtubule targeting agents that circumvent multiple drug resistance

246th National Meeting (2013)

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Novel methodology for the synthesis of methyl substituted 4-(4'-methoxyphenylamine)-5, 6-dihydropyrrolo[2,3-d]pyrimidines as water-soluble microtubule targeting agents that circumvent multiple drug resistance