Gliotoxin analogues as inhibitors of reverse transcriptase. 1. Effect of lipophilicity
Ottenheijm, H C × Herscheid, J D Tijhuis, M W Oosterbaan, M De Clercq, Erik #
Journal of Medicinal Chemistry vol:21 issue:8 pages:796-9
The reaction scheme, developed for the synthesis of the gliotoxin analogue 2, was found to be of general applicability for analogues with varying substituents at N(1) and C(2). Analogues 11b-g prepared by this method are inhibitors of reverse transcriptase (RNA-directed DNA polymerase). Their inhibitory activity seems to be related to the lipophilicity of the effector molecules: the most lipophilic compound is the most active inhibitor. The techniques of reversed-phase thin-layer chromatography with silylated, precoated plates as well as reversed-phase high-performance liquid chromatography were used to measure the relative lipophilicities; both techniques gave analogous results.