Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity

P Wipf, W Li, CM Adeyeye, JM Rusnak…

Index: Wipf, Peter; Li, Wenjie; Adeyeye, Christianah M.; Rusnak, James M.; Lazo, John S. Bioorganic and Medicinal Chemistry, 1996 , vol. 4, # 10 p. 1585 - 1596

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Citation Number: 34

Abstract

N4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4, 4-dialkyloxazolinones. An azapeptide prodrug of ara-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N4 prevented nonspecific proteolytic cleavage in biological medium. ara-C prodrugs 10, 15, 17, and 19 released active drug with half-lives ...