@article {De Clercq:2004:1567-2042:543,
title = "New Anti-HIV Agents in Preclinical or Clinical Development",
journal = "Frontiers in Medicinal Chemistry - Online",
parent_itemid = "infobike://ben/fmc",
publishercode ="ben",
year = "2004",
volume = "1",
number = "1",
publication date ="2004-01-01T00:00:00",
pages = "543-579",
itemtype = "ARTICLE",
issn = "1567-2042",
url = "https://www.ingentaconnect.com/content/ben/fmc/2004/00000001/00000001/art00025",
doi = "doi:10.2174/1567204043396244",
keyword = "integrase, transcription, reverse transcriptase, protease, fusion, human immunodeficiency virus, cxcr4",
author = "De Clercq, Erik",
abstract = "Virtually all the compounds that are currently used (or have been the subject of advanced clinical trials), for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine and nucleotide reverse transcriptase inhibitors (NtRTIs) (i.e. tenofovir disoproxil fumarate); (ii) nonnucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. In addition to the reverse transcriptase and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 [i.e. bicyclam (AMD3100) derivatives] and CCR5 (i.e. TAK-779 derivatives); (iii) virus-cell fusion, through binding to the viral envelope glycoprotein gp41 (T-20, T-1249); (iv) viral assembly and disassembly, through NCp7 zinc fingertargeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)]; (v) proviral DNA integration, through integrase inhibitors such as 4-aryl-2,4-dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides by-passing the first phosphorylation step of the NRTIs), (ii) increased activity [second generation NNRTIs (i.e. TMC-125, DPC-083)] against those HIV strains that are resistant to the first generation NNRTIs, or (iii), as in the case of PIs, a different, modified peptidic [i.e. azapeptidic (atazanavir)] or non-peptidic scaffold [i.e. cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)]. Non-peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs.",
}