title: cycloSal-d4TMP pronucleotides structural variations, mechanistic insights and antiviral activity.
abstract: Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogues against different viral diseases. The basic idea is to achieve nucleotide delivery into cells, bypassing limitations with intracellular formation of nucleotides from their nucleoside precursors. The cycloSal-concept is one of several pronucleotide systems reported so far. For the nucleoside analogue d4T, the cycloSal-approach improved antiviral potency. The basic idea, chemistry, different structural modifications and their effects on the antiviral potency of the cycloSal-d4TMP triesters have been discussed in this review.
authors.affiliation: Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, D-20146, Germany. chris.meier@chemie.uni-hamburg.de
authors.forename: Chris
authors.initials: C
authors.lastname: Meiera
authors.forename: Jürgen
authors.initials: J
authors.lastname: Renzea
authors.forename: Christian
authors.initials: C
authors.lastname: Ducho
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000737:chemistry; D001711:Biotransformation; D054306:Dideoxynucleotides; D006678:HIV / Q000187:drug effects; D006801:Humans; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D018119:Stavudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides
chemical_list: D000998:Antiviral Agents; D001592:Benzyl Alcohols; C415254:Cyclosaligenyl-2',3'-didehydro-2',3'-dideoxythymidine monophosphate; D054306:Dideoxynucleotides; D011355:Prodrugs; D013942:Thymine Nucleotides; D018119:Stavudine; C010631:salicyl alcohol