Inhibitors interacting with the magnesium binding site of reverse transcriptase: synthesis and biological activity studies of 3'-(omega-amino-acyl) amino-3'-deoxy-thymidine.
Active site of reverse transcriptase contains carboxylate groups involved in the magnesium binding. We prepared some nucleoside analogs which could bind to these carboxylates preventing the binding of nucleotides. To the 3'-amino-3'-deoxy-thymidine, different N-protected omega-amino-acids were bound, the protection removed to give the 3'-(omega-amino-acyl-) amino-3'-deoxy-thymidines in good yield. Some showed moderate to low activity in HIV 1 replication test.
Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
Thirumani Venkateshwar
TV
Goud
Anne-Marie
AM
Aubertin
Jean-François
JF
Biellmann
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D054303:HIV Reverse Transcriptase; D008274:Magnesium; D013936:Thymidine