期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 9, 页码 3284-3286出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.03.019
关键词
CCR5 receptor antagonist; Anti-HIV-1; SAR
资金
- key National Science and Technology Program-'Major New Drug Development During the 11th Five-Year Period of China [2009ZX09103-628]
- Natural Science Foundation of China [81102373, 81173098]
A series of novel 1,4-disubstituted piperidine/piperazine derivatives were designed, synthesized and evaluated for their in vitro activities against HIV-1 Bal (R5) infection in CEMX174 5.25M7 cells. A majority of these compounds showed potent anti-HIV-1 activities with IC50 at nanomolar levels. N-(4-Fluoro-benzyl)piperazine analog B07 hydrochloride exhibited potency against HIV-1 activity similar to that of TAK-220 hydrochloride, but it had much better water solubility (25 mg/ml in phosphate sodium buffer at 25 degrees C) and oral bioavailability (56%) than TAK-220 hydrochloride (a solubility of 2 mg/ml and oral bioavailability of 1.4%). These results suggest that B07 hydrochloride may serve as a better lead for the development of new anti-HIV-1 therapies or microbicides for treatment and prevent of HIV-1 infection. (C) 2012 Elsevier Ltd. All rights reserved.
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