"Lock-in" modified cyclosal nucleotides--the second generation of cyclosal prodrugs.
A new generation of cycloSal-pronucleotides is presented. CycloSal-d4TMPs have been modified by introduction of an esterase-cleavable site in order to trap them inside cells. Hydrolysis studies in different media (PBS, CEM/0- and liver extracts) and anti-HIV evaluation of separated diastereomers revealed unexpected differences between the isomers.
Vukadinović
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Institute of Organic Chemistry, University of Hamburg, Hamburg, Germany.
Böge
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NP
Balzarini
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Meier
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C
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D054306:Dideoxynucleotides; D015195:Drug Design; D004950:Esterases / Q000737:chemistry; D006678:HIV / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D006868:Hydrolysis; D008956:Models, Chemical; D009154:Mutation; D009711:Nucleotides / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry*; D020033:Protein Isoforms; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013942:Thymine Nucleotides
D019380:Anti-HIV Agents; C415254:Cyclosaligenyl-2',3'-didehydro-2',3'-dideoxythymidine monophosphate; D054306:Dideoxynucleotides; D009711:Nucleotides; D011355:Prodrugs; D020033:Protein Isoforms; D013942:Thymine Nucleotides; D018119:Stavudine; D004950:Esterases