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Dipyridodiazepinone Analogs as Human Immunodeficiency Virus Type 1- Specific Non-Nucleoside Reverse Transcriptase Inhibitors: An Overview

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According to World Health Organization (WHO)/Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (UNAIDS) Report in 2007, 33.2 million people are living with HIV, 2.5 million ones have been newly infected with HIV, and 2.1 million ones died from AIDS, including 330,000 children. Therefore, HIV/AIDS still remains a public health emergency and a leading cause of mortality worldwide. It is believed that reverse transcriptase (RT) is a crucial enzyme in the life cycle of HIV-1, and thereby RT has been the important drug target for antiretroviral (ARV) chemotherapy against AIDS. To our knowledge, dipyridodiazepinone analogs have been considered as one class of potential non-nucleoside reverse transcriptase inhibitors (NNRTIs), especially the structurally and chemically related nevirapine (Viramune®), which was the first NNRTI approved by the U. S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection for adults in 1996 and for children in 1998. This review mainly highlights the progress of synthesis and structure-activity relationship (SAR) of dipyridodiazepinone analogs; in the meantime, the mechanism of action is also presented. It will pave the way for the design and development of novel dipyridodiazepinone analogs as NNRTIs in AIDS chemotherapy in the future.
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Keywords: Dipyridodiazepinone; acquired immunodeficiency syndrome; human immunodeficiency virus type 1; mechanism of action; nonnucleoside reverse transcriptase inhibitor; structure-activity relationship

Document Type: Research Article

Affiliations: Laboratory of Pharmaceutical Design & Synthesis, College of Sciences, Northwest A&F University, Yangling 712100, P. R. China.

Publication date: 2010-06-01

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