Synthesis of deuterium-labelled etravirine

摘要

Etravirine, a second-generation non-nucleoside reverse transcrip-tase inhibitor (NNRTI), is highly potent and effective against wild-type and drug-resistant HIV-1 variants. It was granted accelerated approval by the FDA (18 January 2008) and marketed under the name Intelence~TM. In clinical development, etravirine has shown durable efficacy and, with the exception of rash, a safety profile similar to placebo. Furthermore, the nature and magnitude of adverse events observed with etravirine suggest that the drug may offer improved tolerability over first-generation NNRTIs. In addition it could offer safety benefits over first-generation NNRTIs in early experienced patients. Etravirine can be used in combination with other antiretrovirals such as boosted protease inhibitors and raltegravir with little potential for additional toxicity. Therefore, given this favorable safety profile along with its enhanced barrier to the development of resistance and demonstrated efficacy, etravirine provides an important treatment option for HIV-infected, treatment-experienced patients.