期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 18, 期 12, 页码 4363-4373出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.04.089
关键词
Seco-DCK analogs; Anti-HIV agents
资金
- National Natural Science Foundation of China [20272010, 30200348, 30873164]
- National Education Administration of China [2002046069]
- National Institute of Allergies and Infectious Diseases [AI-33066]
- National Ministry of Science and Technology, China [2009zx09301-011]
Thirteen novel seco-DCK analogs (4-16) with several new skeletons were designed, synthesized and screened for in vitro anti-HIV-1 activity. Among them, three compounds (5, 13, and 16) showed moderate activity, and compound 9 exhibited the best activity with an EC(50) value of 0.058 mu M and a therapeutic index (TI) of 1000. The activity of 9 was better than that of 4-methyl DCK (2, EC(50): 0.126 mu M, TI: 301.2) in the same assay. Additionally, 9 also showed antiviral activity against a multi-RT inhibitor-resistant strain (RTMDR), which is insensitive to most DCK analogs. Compared with 2, compound 9 has a less complex structure, fewer hydrogen-bond acceptors, and a reduced log P value. Therefore, it is likely to exhibit better ADME, and appears to be a promising new lead for further development as an anti-HIV candidate. (C) 2010 Elsevier Ltd. All rights reserved.
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