ABSTRACT
The acquired immunodeficiency syndrome (AIDS) related to HIV-1 infection is one of the most serious threats to human health, and it has been estimated that more than 25 million people have died since it was first recognized. In the fight against AIDS, first-and second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) are now established as part of highly active antiretroviral therapy (HAART) for treating HIV infection. However, the efficacy of currently available NNRTIs, e.g., nevirapine (NVP, Viramune®), delavirdine (DLV, Rescriptor®), and efavirenz (EFV, Sustiva®, Stocrin®), is impaired by rapid emergence of drug resistance. On the other hand, as patients live longer on HAART therapy and the pool of NNRTI-resistant viruses increases, so does the need for the development of new NNRTIs with antiviral activity against clinically relevant mutant strains. Our research group was recently involved in a multitarget approach to defeat the HIV
Abstract .................................................................................................................. 325 Introduction ............................................................................................................ 326 S-DABO ................................................................................................................. 329 Chemistry ............................................................................................................... 330 Results and Discussion .......................................................................................... 330 Molecular Modeling Calculations ......................................................................... 334 Reverse Transcriptase Mutants .............................................................................. 337 6-Vinylpyrimidines ................................................................................................ 338 Acknowledgment ................................................................................................... 343 References .............................................................................................................. 343
virus, focusing on the inhibition of HIV-1 reverse transcriptase according to both classical and nonclassical approaches.
