Abstract
To explore non-aniline aromatic substitution on the pyrimidine C4 position, novel 4-(N, N'-di-n-propyl-3,4-dicarboxamido-1H-pyrrole) pyrimidines are designed and synthesized as anaplastic lymphoma kinase inhibitors for non-small cell lung cancer treatment. To overcome the unexpected cleavage between the C-N linkage of pyrrole nitrogen and C4-pyrimidine during hydrolysis and inaccessibility of the desired diamide formation through coupling agent-mediated conditions, the 4-(N, N'-di-n-propyl-3,4-dicarboxamido-1H-pyrrole) pyrimidine was assembled through direct nucleophilic substitution under microwave irradiation. Thus prepared 4-(N, N'-di-n-propyl-3,4-dicarboxamido-1H-pyrrole) pyrimidines were measured both ALK binding and H3122 cell proliferation assay. Their weak ALK activities are explained with molecular modeling study.