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Editorial
. 2018 Dec 20;10(1):2-5.
doi: 10.1021/acsmedchemlett.8b00586. eCollection 2019 Jan 10.

The ProTide Prodrug Technology: Where Next?

Ashwag S Alanazi  1 , Edward James  1 , Youcef Mehellou  1
Affiliations
Editorial

The ProTide Prodrug Technology: Where Next?

Ashwag S Alanazi et al. ACS Med Chem Lett. .

Abstract

The ProTide prodrug technology has proved very useful in the discovery of nucleotide therapeutics and has successfully led to two FDA-approved drugs. However, with the extensive application of this prodrug approach to nucleotides for nearly three decades, the intellectual property (IP) landscape is becoming congested and, to overcome this, new inventive applications of the ProTide prodrug technology are emerging.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) General chemical structure of the aryloxy triester phosphoramidate (ProTide) prodrug technology. The key masking groups, the aryl motif and the amino acid ester, are labeled and highlighted. X = O (phosphate) or CH2 (phosphonate). X1 = any aromatic substitution. R = any group. (B) Postulated mechanism of the ProTides’ metabolism. (C) Number of ProTide publications from 1990 to 2018 at the indicated time periods. This was gathered by searching PubMed using the terms “phosphoramidate and nucleoside” for the time periods shown. *Indicates November 25th, 2018 when the search was last performed. (D) Chemical structures of the two FDA-approved drugs, sofosbuvir and tenofovir alafenamide along with diseases they are being used to treat. (E) Examples of ProTide clinical candidates along with diseases they are being pursued to treat.
Figure 2
Figure 2
Examples of non-nucleoside monophosphate and monophosphonate-containing molecules to which the ProTide technology has been applied as a means of improving their drug-like properties.
See this image and copyright information in PMC

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