Synthesis, in vitro anti-HIV activity, and biological stability of 5'- O-myristoyl analogue derivatives of 3'-fluoro-2',3'dideoxythymidine (FLT) as potential bifunctional prodrugs of FLT

Article abstract of DOI:10.1080/07328319808004216

A group of 5'-O-myristoyl analogue derivatives of FLT (2) were evaluated as potential anti-HIV agents that were designed to serve as prodrugs to FLT. 3'-Fluoro-2',3'-dideoxy-5'-O-(12-methoxydodecanoyl)thymidine (4) (EC₅₀ = 3.8 nM) and 3'-fluoro-2',3'-dideoxy-5'-O-(12-azidododecanoyl)thymidine (8) (EC₅₀ = 2.8 nM) were the most effective anti-HIV-1 agents. There was a linear correlation between Log P and HPLC Log retention time for the 5'-O- FLT esters. The in vitro enzymatic hydrolysis half-life (t(1/2)), among the group of esters (3-8) in porcine liver esterase, rat plasma and rat brain homogenate was longer for 3'-fluoro-2',3'-dideoxy-5'-O-(myristoyl)thymidine (7), with t(1/2) values of 20.3, 4.6 and 17.5 min, respectively.

Full text of DOI:10.1080/07328319808004216

Nucleosides and Nucleotides
ISSN: 0732-8311 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/lncn19
Synthesis, In Vitro Anti-HIV Activity, and Biological
Stability of 5′-O-Myristoyl Analogue Derivatives of
3′-Fluoro-2′,3′-Dideoxythymidine (FLT) as Potential
Bifunctional Prodrugs of FLT
Keykavous Parang , Edward E. Knaus & Leonard I. Wiebe
To cite this article: Keykavous Parang , Edward E. Knaus & Leonard I. Wiebe (1998) Synthesis,
In Vitro Anti-HIV Activity, and Biological Stability of 5′-O-Myristoyl Analogue Derivatives of 3′-
Fluoro-2′,3′-Dideoxythymidine (FLT) as Potential Bifunctional Prodrugs of FLT, Nucleosides and
Nucleotides, 17:6, 987-1008, DOI: 10.1080/07328319808004216
To link to this article: http://dx.doi.org/10.1080/07328319808004216
Published online: 21 Aug 2006.
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Date: 11 November 2015, At: 20:13