Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors: Optimization of Whole-Cell Anticryptococcal Activity and Insights into the Structural Origins of Cryptococcal Selectivity was written by 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.;Prive, Gilbert G.;Whitesell, Luke;Cowen, Leah E.;Brown, Lauren E.. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C8H6ClFO2 This article mentions the following:
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 been precluded by human host toxicities and suppression of immune responses. We recently described resorcylate aminopyrazoles (RAPs) as the first class of Hsp90 inhibitors capable of discriminating between fungal (Cryptococcus neoformans, Candida albicans) and human isoforms of Hsp90 in biochem. assays. Here, we report an iterative structure-property optimization toward RAPs capable of inhibiting C. neoformans growth in culture. In addition, we report the first X-ray crystal structures of C. neoformans Hsp90 nucleotide binding domain (NBD), as the apoprotein and in complexes with the non-species-selective Hsp90 inhibitor NVP-AUY922 and three RAPs revealing unique ligand-induced conformational rearrangements, which reaffirm the hypothesis that intrinsic differences in protein flexibility can confer selective inhibition of fungal vs. human Hsp90 isoforms. In the experiment, the researchers used many compounds, for example, Methyl 2-chloro-4-fluorobenzoate (cas: 85953-29-3Synthetic Route of C8H6ClFO2).
Methyl 2-chloro-4-fluorobenzoate (cas: 85953-29-3) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Synthetic Route of C8H6ClFO2
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics