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Nucleoside phosphate and phosphonate prodrug clinical candidates

Thornton, Peter J., Kadri, Hachemi, Miccoli, Ageo and Mehellou, Youcef 2016. Nucleoside phosphate and phosphonate prodrug clinical candidates. Journal of Medicinal Chemistry 59 (23) , pp. 10400-10410. 10.1021/acs.jmedchem.6b00523

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Abstract

Nucleoside monophosphates and monophosphonates have been known for a long time to exert favorable pharmacological effects upon intracellular delivery. However, their development as drug molecules has been hindered by the inherent poor druglike properties of the monophosphate and monophosphonate groups. These include inefficient cellular uptake and poor in vivo stability, with this latter drawback being most relevant to monophosphates than monophosphonates. To address these limitations, numerous monophosphate and monophosphonate prodrug strategies have been developed and applied in the discovery of nucleoside monophosphate and monophosphonate prodrugs that can treat viral infections and cancer. The approval of sofosbuvir, a nucleoside monophosphate prodrug, highlighted the success to be had by employing these prodrug technologies in the discovery of nucleotide therapeutics. In this Miniperspective, we discuss the different key monophosphate and monophosphonate nucleoside prodrugs that entered clinical development, some of which may in the future be approved to treat various human diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Publisher: American Chemical Society
ISSN: 0022-2623
Date of First Compliant Deposit: 12 May 2017
Date of Acceptance: 25 August 2016
Last Modified: 29 Jun 2019 12:56
URI: http://orca.cf.ac.uk/id/eprint/100531

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