cycloSal-d4TMP pronucleotides structural variations, mechanistic insights and antiviral activity.
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.
Meiera
Chris
C
Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, D-20146, Germany. chris.meier@chemie.uni-hamburg.de
Renzea
Jürgen
J
Ducho
Christian
C
Balzarini
Jan
J
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
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