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Synthesis, antiviral potency, in vitro ADMET and X-ray structure of potent CD4-mimics as entry inhibitors that target the Phe43 cavity of HIV-1 gp120статья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 17 июня 2021 г.
- Авторы: Curreli F., Kwon Y.D., Belov D.S., Ramesh R.R., Kurkin A.V., Altieri A., Kwong P.D., Debnath A.K.
- Журнал: Journal of Medicinal Chemistry
- Том: 60
- Номер: 7
- Год издания: 2017
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 3124
- Последняя страница: 3153
- DOI: 10.1021/acs.jmedchem.7b00179
- Аннотация: In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure–activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses. The X-ray structure of a similar compound, NBD-14010, confirmed the binding mode of the newly designed compounds. The in vitro ADMET profiles of these compounds are comparable to that of the most potent attachment inhibitor BMS-626529, a prodrug of which is currently undergoing phase III clinical trials. The systematic study presented here is expected to pave the way for improving the potency, toxicity, and ADMET profile of this series of compounds with the potential to be moved to the early preclinical development.
- Добавил в систему: Белов Дмитрий Сергеевич