期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 15, 期 7, 页码 2690-2700出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2007.01.036
关键词
human papillomavirus; protein-protein interaction; indandione; NMR
We have previously reported the discovery and initial SAR optimization of the first series of inhibitors of the human papillomavirus type-11 (HPV11) E1-E2 protein-protein interaction. These inhibitors featured an indandione system spiro-fused onto an all syn substituted tetrahydrofuran ring. In this paper, we report new SAR efforts which have led to the identification of the first low nanomolar inhibitor of the HPV11 E1-E2 protein-protein interaction. In addition, we report a combined NMR and computational chemistry approach which allowed the successful determination of the absolute stereochernistry of the active species originating from the initial racemic lead. (c) 2007 Elsevier Ltd. All rights reserved.
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