Inhibitors interacting with the magnesium binding site of reverse transcriptase: synthesis and biological activity studies of 3'-(omega-amino-acyl) amino-3'-deoxy-thymidine

Abstract

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.