Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595811 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
A new oxazole scaffold showing great promise in HIV-1 inhibition has been discovered by cell-based screening of an in-house library and scaffold modification. Follow-up SAR study focusing on the 5-aryl substituent of the oxazole core has identified 4k (EC50 = 0.42 μM, TI = 50) as a potent inhibitor. However, the analogues suffered from poor aqueous solubility. To address this issue, we have developed broadly applicable potential prodrugs of indazoles. Among them, N-acyloxymethyl analogue 11b displayed promising results (i.e., increased aqueous solubility and susceptibility to enzymatic hydrolysis). Further studies are warranted to fully evaluate the analogues as the potential prodrugs with improved physiochemical and PK properties
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Se-Ho Kim, Benjamin Markovitz, Richard Trovato, Brett R. Murphy, Harry Austin, Adam J. Willardsen, Vijay Baichwal, Scott Morham, Ashok Bajji,