Open AccessIntroduction of a cyano group at the 2-position of an (R,S)-3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) derivative of thymine elicits selective anti-HBV activity
Author(s) -
Shuai Tan,
Elisabetta Groaz,
Mark N. Prichard,
Raj Kalkeri,
Roger G. Ptak,
Piet Herdewijn
Publication year - 2021
Publication title -
rsc medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 55
ISSN - 2632-8682
DOI - 10.1039/d1md00086a
Subject(s) - thymine , stereochemistry , chemistry , hepatitis b virus , derivative (finance) , nucleoside , nucleoside analogue , virus , virology , biology , biochemistry , dna , financial economics , economics
The substantial impact of acyclic nucleoside phosphonates (ANPs) on human medicine encourages the synthesis of new ANP analogues with a potentially differentiated antiviral spectrum. Herein, we demonstrate the functionalization of the 2-position of the ( R , S )-3-hydroxy-2-(phosphonomethoxy)propyl side-chain of an inactive ANP with a polar cyano group to generate a thymine analogue with selective inhibition of hepatitis B virus (HBV) replication (SI > 302; EC 50 = 0.33 μM), without significant antiretroviral activity. These findings suggest new strategies to synthesize unique ANPs with a targeted antiviral profile.