880089-70-3Relevant academic research and scientific papers
NOVEL AZOLES AND RELATED DERIVATIVES AS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS) IN ANTIVIRAL THERAPY (HIV)
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Sheet 2, (2009/03/07)
The present invention relates to novel heterocyclic compounds, including oxadiazole compounds, pharmaceutical compositions and their use in the inhibition of reverse transcriptase and the treatment of HIV (1 and 2) infections, AIDS and ARC and other viral
Optimization of azoles as anti-human immunodeficiency virus agents guided by free-energy calculations
Zeevaart, Jacob G.,Wang, Ligong,Thakur, Vinay V.,Leung, Cheryl S.,Tirado-Rives, Julian,Bailey, Christopher M.,Domaoal, Robert A.,Anderson, Karen S.,Jorgensen, William L.
supporting information; experimental part, p. 9492 - 9499 (2009/02/03)
Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP "chlorine scan" was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. FEP calculations for additional substituent modifications and change of the core heterocycle readily led to oxazoles 28 and 29, which were confirmed as highly potent anti-HIV agents with activities in the 10-20 nM range. The designed compounds were also monitored for possession of desirable pharmacological properties by use of additional computational tools. Overall, the trends predicted by the FEP calculations were well borne out by the assay results. FEP-guided lead optimization is confirmed as a valuable tool for molecular design including drug discovery; chlorine scans are particularly attractive since they are both straightforward to perform and highly informative.
Unsubstituted and substituted 4-benzyl-1,3-dihydro-imidazole-2-thiones acting as specific or selective alpha2 adrenergic agonists and methods for using the same
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Page/Page column 10, (2010/10/20)
Compounds of Formula 1 where the variables have the meaning defined in the specification are used to activate alpha2 adrenergic receptors. The compounds of Formula 1 are incorporated in pharmaceutical compositions and are used as medicaments in mammals, including humans, for treatment of diseases and or alleviations of conditions which are responsive to treatment by agonists of alpha2 adrenergic receptors.
