Raltegravir, formerly named MK-0518, is an HIV-1 integrase strand transfer inhibitor which has been shown to have activity against multidrug-resistant HIV-1 and both CCR5-trophic and CXCR4-trophic HIV-1 in vitro. Structural modifications on these molecules are made in order to maximize potency as HIV-integrase inhibitors against the wild type virus, a selection of mutants, and optimize the selectivity, pharmacokinetic, and metabolic profiles in preclinical species. Raltegravir derives from the evolution of 5,6-dihydroxypyrimidine-4-carboxamides and N-methyl-4-hydroxypyrimidinone-carboxamides. It has been shown to have potent antiretroviral effects, with a mean decrease from baseline in HIV-1 RNA concentrations of about 2 log10 copies per mL after 10 days of monotherapy.
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[1].Beatriz Grinsztejn, Dr Bach-Yen Nguyen, Christine Katlama, Jose M Gatell, Adriano Lazzarin, Daniel Vittecoq, Charles J Gonzalez, Joshua Chen, Charlotte M Harvey, Robin D Isaacs. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Then Lancet. 2007. 369(9569): 1261–1269.
[2].Vincenzo Summa, Alessia Petrocchi, Fabio Bonelli, Benedetta Crescenzi, Monica Donghi, Marco Ferrara, Fabrizio Fiore, Cristina Gardelli, Odalys Gonzalez Paz, Daria J. Hazuda, Philip Jones, Olaf Kinzel, Ralph Laufer, Edith Monteagudo, Ester Muraglia, Emanuela Nizi, Federica Orvieto, Paola Pace, Giovanna Pescatore, Rita Scarpelli, Kara Stillmock, Marc V. Witmer, Michael Rowley. Discovery of Raltegravir, a Potent, Selective Orally Bioavailable HIV-Integrase Inhibitor for the Treatment of HIV-AIDS Infection. J. Med. Chem., 2008, 51 (18), pp 5843–5855.