- Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors: Optimization of Whole-Cell Anticryptococcal Activity and Insights into the Structural Origins of Cryptococcal Selectivity
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The essential eukaryotic chaperone Hsp90 regulates the form and function of diverse client proteins, many of which govern thermotolerance, virulence, and drug resistance in fungal species. However, use of Hsp90 inhibitors as antifungal therapeutics has be
- Marcyk, Paul T.,Leblanc, Emmanuelle V.,Kuntz, Douglas A.,Xue, Alice,Ortiz, Francisco,Trilles, Richard,Bengtson, Stephen,Kenney, Tristan M. G.,Huang, David S.,Robbins, Nicole,Williams, Noelle S.,Krysan, Damian J.,Privé, Gilbert G.,Whitesell, Luke,Cowen, Leah E.,Brown, Lauren E.
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p. 1139 - 1169
(2021/02/01)
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- 3-Substituted-(5-arylfuran-2-ylcarbonyl)guanidines as NHE-1 inhibitors
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The C-3 substituents effect on NHE-1 inhibitory activity of (5-arylfuran-2-ylcarbonyl)guanidines, previously identified as potent NHE-1 inhibitors, was investigated. The introduction of amine or alkyl groups at the 3-position of the furan ring, next to the acylguanidine moiety, remarkably improves NHE-1 inhibitory potency. Especially the important finding is that 5-(2,5-dichloro)phenyl and 5-(2-methoxy-5-chloro)phenyl derivatives exhibit high NHE-1 inhibitory activities (IC50 0.02 μM) that match those of 3-unsubstituted derivatives.
- Lee, Sunkyung,Kim, Taemi,Lee, Byung Ho,Yoo, Sung-eun,Lee, Kyunghee,Yi, Kyu Yang
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p. 1291 - 1295
(2008/02/02)
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- Potential antiarthritic agents. II. Benzoylacetonitriles and β-aminocinnamonitriles
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Benzoylacetonitrile and β-aminocinnamonitrile are shown to possess potent intiinflammatory activity in the rat adjuvant arthritis model. In a series of phenyl-substituted analogues, only o-, m-, and p-fluorobenzoylacetonitrile and m- and p-fluoro-β-aminocinnamonitrile retained activity. Additionally, β-amino-2- and β-amino-3-thiopheneacrylonitrile and β-oxo-2- and β-oxo-3-thiophenepropionitrile exhibited similar activity. These agents are not believed to be acting via prostaglandin synthetase inhibition. The metabolic profile of benzoylacetonitrile is also described.
- Ridge,Hanifin,Harten,Johnson,Menschik,Nicolau,Sloboda,Watts
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p. 1385 - 1389
(2007/10/09)
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