English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

A comparative study of three cycloSal-d4TMP 1, 2 and 3 and a variety of bis(benzyl) phosphate triester 4–8 of the antivirally active nucleoside analogue 2′,3′-dideoxy-2′,3′-didehydrothymidine (d4T) will be described. This study has been initiated by the observation that the introduction of a simple 7-methyl group in the cycloSal-structure (2) led to a completely different hydrolysis pattern as compared to the prototype cycloSal- d4TMP 1. Instead of the selective formation of d4TMP, a phenyl phosphate diester was formed in the case of the 7-methyl-substituted compound 2. The difference in degradation pathway was caused by a change of the reaction mechanism. The phenyl phosphate diester was chemically and enzymatically inert to further cleavage to yield d4TMP. For comparison bis(benzyl)-d4TMP 4, bis(α-methylbenzyl)-d4TMP 5, bis(α-methoxycarbonylmethyl [MCM]-benzyl)-d4TMP 6 as well as the enzyme-cleavable bis(4-acetoxybenzyl)- d4TMP [bis(AB)-d4TMP(7 and bis(α-methoxycarbonylmethyl-4-acetoxybenzyl)-d4TMP [bis(α-MCM-AB)-d4TMP] 8 were synthesized. Chemical hydrolysis studies proved that all bis(benzyl) triesters hydrolyze to give the intermediate benzyl phosphate diesters. Moreover, the latter two triesters 7,8 and cycloSal-d4TMPs 1 and 3 led finally to the delivery of d4TMP. The chemical hydrolysis studies allowed a detailed mechanistic interpretation of the degradation pathways of triesters 1–8. Cell extract studies of the bis(benzyl) triesters 4–8 confirmed that only triesters 7 and 8 released d4TMP although with a considerable increase of the reaction rate. Anti-HIV evaluation of the compounds showed that cycloSal-d4TMP 1 and the bis(AB) triesters 7,8 were entirely independent of the presence of cellular thymidine kinase (TK).

antiviral chemistry and chemotherapy

Comparative Study of Bis(Benzyl)Phosphate Triesters of 2′,3′-Dideoxy-2′,3′-Didehydrothymidine (d4T) and<i>Cyclo</i>Sal-d4TMP — Hydrolysis, Mechanistic Insights and Anti-HIV Activity

Comparative Study of Bis(Benzyl)Phosphate Triesters of 2′,3′-Dideoxy-2′,3′-Didehydrothymidine (d4T) andCycloSal-d4TMP — Hydrolysis, Mechanistic Insights and Anti-HIV Activity