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4'-Ethynyl-2'-deoxy-2'-β-fluoro-2-fluoroadenosine: A Highly Potent and Orally Available Clinical Candidate for the Treatment of HIV-1 Infection. | LitMetric
2'-Deoxy-2'-β-fluoroadenosines bearing 4'-azido or 4'-ethynyl groups designed for the treatment of HIV-1 infection have been synthesized. All these compounds possess nanomolar anti-HIV-1 activity, with the 4'-ethynyl-2-fluoroadenosine analog () being the most potent compound with low cytotoxicity (EC = 0.9 nM, CC > 100 μM). It also shows potent inhibitory activities on drug resistant and clinical HIV-1 strains. Oral administration of to Beagle dogs resulted in high levels of its bioactive form in peripheral blood mononuclear cells, the HIV-1 target cells, where the resulting triphosphate exhibited a long-term intracellular retention and could prevent HIV-1 infection for an extended time. displayed low toxicity and favorable pharmacokinetics profiles in Sprague-Dawley rats. The preclinical data support further development of as a highly potent and orally bioavailable clinical candidate to treat HIV-1 infection. Currently, is in clinical trials in China (registration number: CXHL2200529).
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