Design, asymmetric synthesis, and evaluation of pseudosymmetric sulfoximine inhibitors against HIV-1 protease

Ding, Lei; Sham, Yuk Y.; Vince, Robert

doi:10.1016/j.bmc.2010.01.020

Cited by 36 publications

(26 citation statements)

References 40 publications

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“…Docking studies of this compound in the HIV-1 protease active site revealed that the inhibitor formed extensive hydrogen bonding interactions in the active site. 155 The amide NHs formed hydrogen bonds with the carbonyl of Gly27/27’. The hydroxyl groups of the aminoindanol moiety made hydrogen bonds with the carboxylate oxygens of Asp29/29’.…”

Section: (5) Recent Progress Towards Hiv-1 Protease Inhibitorsmentioning

confidence: 99%

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS

2016

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HIV-1 protease inhibitors continue to play an important role in the treatment of HIV/AIDS, transforming this deadly ailment into a more manageable chronic infection. Over the years, intensive research led to a variety of approved protease inhibitors for the treatment of HIV/AIDS. In this review, we outline current drug design and medicinal chemistry efforts toward the development of new generation protease inhibitors beyond the currently approved drugs.

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Section: (5) Recent Progress Towards Hiv-1 Protease Inhibitorsmentioning

confidence: 99%

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS

2016

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“…An HIV-1 protease fluorescence resonance energy transfer (FRET) assay kits are commercially available for biochemical evaluation of potential protease inhibitors [29]. HIV-1 protease activity can be monitored in human cells based on expression of a precursor protein harboring the viral protease fused to the reporter protein GFP [28]. Western analysis of intracellular and virion protein processing can be utilized as well to evaluate HIV-1 protease inhibition.…”

Section: Protease Inhibitorsmentioning

confidence: 99%

The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets

Hartman

Buckheit

2012

Molecular Biology International

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During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today’s highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of problems which require continued development efforts to improve efficacy and reduce toxicity, while making drugs that can be used throughout both the developed and developing world, in pediatric populations, and in pregnant women. Highly active antiretroviral therapies (HAARTs) have significantly delayed the progression to AIDS, and in the developed world HIV-1-infected individuals might be expected to live normal life spans while on lifelong therapies. However, the difficult treatment regimens, the presence of class-specific drug toxicities, and the emergence of drug-resistant virus isolates highlight the fact that improvements in our therapeutic regimens and the identification of new and novel viral and cellular targets for therapy are still necessary. Antiretroviral therapeutic strategies and targets continue to be explored, and the development of increasingly potent molecules within existing classes of drugs and the development of novel strategies are ongoing.

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“…Asp25) in the active site, leading to immature, non-infective virus particles (Ashorn et al, 1990;Lambert et al, 1992). Due to its importance, the HIV protease has become an important target for HIV therapeutics, resulting in the development of several inhibitors (Randolph et al, 2006;Jochim et al, 2009;Lu et al, 2010;Ridky and Leis, 1995).…”

Section: A Recent Aspartyl Family Member: Hiv Proteasementioning

confidence: 99%

Looking at the proteases from a simple perspective

Castro

Abreu

Geraldo

et al. 2011

J of Molecular Recognition

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Proteases have received enormous interest from the research and medical communities because of their significant roles in several human diseases. Some examples include the involvement of thrombin in thrombosis, HIV-1 protease in Acquired Immune Deficiency Syndrome, cruzain in Trypanosoma cruzi infection, and membrane-type 1 matrix metalloproteinase in tumor invasion and metastasis. Many efforts has been undertaken to design effective inhibitors featuring potent inhibitory activity, specificity, and metabolic stability to those proteases involved in such pathologies. Protease inhibitors usually target the active site, but some of them act by other inhibitory mechanisms. The understanding of the structure-function relationships of proteases and inhibitors has an impact on new inhibitor drugs designing. In this paper, the structures of four proteases (thrombin, HIV-protease, cruzain, and a matrix metalloproteinase) are briefly reviewed, and used as examples of the importance of proteases for the development of new treatment strategies, leading to a longer and healthier life.

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Design, asymmetric synthesis, and evaluation of pseudosymmetric sulfoximine inhibitors against HIV-1 protease

Cited by 36 publications

References 40 publications

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS

The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets

Looking at the proteases from a simple perspective

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