2. Academic Validation
  3. Introduction 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

Introduction 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

  • RSC Med Chem. 2021 Apr 29;12(5):804-808. doi: 10.1039/d1md00086a.
Shuai Tan 1,  Elisabetta Groaz 1 2,  Mark N Prichard 3,  Raj Kalkeri 4,  Roger Ptak 4,  Piet Herdewijn 1
Affiliations

Affiliations

  • 1 KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry Herestraat 49-Box 1041 3000 Leuven Belgium Piet.Herdewijn@kuleuven.be.
  • 2 Department of Pharmaceutical and Pharmacological Sciences, University of Padova Via Marzolo 5 35131 Padova Italy.
  • 3 Department of Paediatrics, University of Alabama at Birmingham Birmingham AL 35294-3412 USA.
  • 4 Department of Infectious Disease Research, Drug Development, Southern Research Institute 431 Aviation Way Frederick Maryland 21701 USA.
PMID: 34124679 DOI: 10.1039/d1md00086a
Abstract

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; EC50 = 0.33 μM), without significant antiretroviral activity. These findings suggest new strategies to synthesize unique ANPs with a targeted Antiviral profile.

Figures