Design, Anti-Hiv Activity, Cellular Pharmacology and Conformation of BCH-189 [(±)3TC], A Novel Nucleoside Analogue

Abstract Reverse transcriptase is an attractive target and nucleoside analogues probably still represent today one of the most promising classes of compounds for the treatment of HIV infection. Chemists at IAF BioChem have devised a novel chemical strategy leading to the synthesis of nucleoside analogues in which the 3'-carbon is replaced by a heteroatom of oxygen or sulfur. Already one very promising compound, BCH-189 (2'3'-dideoxy-3'-thiacytidine or (±)3TC), has shown remarkable properties as a potential anti-HIV drug. Intracellular pharmacokinetic, cytotoxicity, anti-HIV activity and conformation are presented and discussed. The comparative evaluation of (±)3TC and ddC in T and B lymphoblastoid cell lines showed that (±)3TC is converted to the triphosphate more efficiently than ddC, (±)3TC-TP is more stable in cells than ddC-TP and the in vitro therapeutic index of (±)3TC is superior to ddC.