A new series of N6,5'-bis-ureido-5'-amino-5'-deoxyadenosine derivatives was prepared and evaluated for anticancer activities using the NCI 60 panel of human cancers. Certain of the derivatives showed promising activities (low micromolar GI50's) against several of the representative cancers. These included cell lines from the following general cell types in the NCI 60: Leukemia, Breast, Central Nervous System, Non-Small Cell Lung, Ovarian, Prostate, Renal, and Colon cancers. Select compounds were also screened for their affinities for protein kinases. The synthesis of the compounds was straightforward and involved N6 acylation with arylisocyanates, preceded by activation and nucleophilic substitution of the 5'-position to give the desired 5'-azido-5'-deoxyadenosine derivatives. Reduction of the 5'-azido function with either H2/Pd-C, or Ph3P/H2O, gave the desired 5'-amino-5' deoxyadenosine products. Acylation of the 5'-amino group with N-methyl 4-nitrophenylcarbamate gave the N6,5'-bis-ureido-5'-amino-5' deoxyadenosine products. Yields ranged from good (50–75%) to excellent (75–95%) for all synthetic transformations.
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
BYU ScholarsArchive Citation
Oliveira, Marcelio, "Synthesis and Evaluation of N6,5'-Bis-Ureido-5'-Amino-5'-Deoxyadenosine Derivatives: Novel Nucleosides with Antiproliferative and Protein Kinase Binding Activities" (2009). Theses and Dissertations. 1964.
Anti-cancer agents, N6, 5'-bis-ureido deoxyadenosine, protein kinases