N(4)-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine-new drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate)

Schott, H; Goltz, D; Schott, T C; Jauch, C; Schwendener, R A

doi:10.1016/j.bmc.2011.04.015

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Schott, H., Goltz, D., Schott, T. C., Jauch, C., & Schwendener, R. A. (2011). N(4)-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine-new drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate). Bioorganic & Medicinal Chemistry, 19(11), 3520–3526. https://doi.org/10.1016/j.bmc.2011.04.015

Abstract

Amino-bisphosphonates (alendronate, pamidronate) were covalently linked in a three step synthesis, with protected and triazolylated derivatives of therapeutically used nucleoside analogs (5-FdU, araC, AZT) by substitution of their triazolyl residue. From the deprotected and chromatographically purified reaction mixtures N(4)-[alkyl-(hydroxyphosphono) phosphonate]-cytidine combining two differently cytotoxic functions were obtained. This new family of bisphosphonates (BPs) contains as novelty an alkyl side chain with a cytotoxic nucleo