Tenofovir: Structure-Activity Relationship and Synthetic Methods

Abstract

Acyclic nucleosides phosphonates (ANPs) belong to a class of antiviral agents, which exhibited activity against several infections. Tenofovir disoproxyl fumarate (TDF) was the first ANP licensed for use as nucleotide reverse transcriptase inhibitors (NRTI) of HIV. TDF is an adenosine-5'-monophosphate analogue and pro-drug of (R)-9-(2-phosphonomethoxylpropyl) adenine (PMPA), also known as tenofovir (TEN). Currently, is one of the most used drugs in the antiretroviral therapy due to excellent results in reducing viral load. In the last few years, the emergence of resistant cases has led to development of new analogs of TDF. Thus, the aims of this revision are to analyze the structure-activity relationships of TDF and its analogs and to describe the main synthetic routes for obtaining this drug.