- Design of Benzoxathiazin-3-one 1,1-Dioxides as a New Class of Irreversible Serine Hydrolase Inhibitors: Discovery of a Uniquely Selective PNPLA4 Inhibitor
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The design and examination of 4,1,2-benzoxathiazin-3-one 1,1-dioxides as candidate serine hydrolase inhibitors are disclosed, and represent the synthesis and study of a previously unexplored heterocycle. This new class of activated cyclic carbamates provi
- Kornahrens, Anne F.,Cognetta, Armand B.,Brody, Daniel M.,Matthews, Megan L.,Cravatt, Benjamin F.,Boger, Dale L.
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supporting information
p. 7052 - 7061
(2017/05/31)
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- Novel N-benzoyl-2-hydroxybenzamide disrupts unique parasite secretory pathway
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Toxoplasma gondii is a protozoan parasite that can damage the human brain and eyes. There are no curative medicines. Herein, we describe our discovery of N-benzoyl-2-hydroxybenzamides as a class of compounds effective in the low nanomolar range against T. gondii in vitro and in vivo. Our lead compound, QQ-437, displays robust activity against the parasite and could be useful as a new scaffold for development of novel and improved inhibitors of T. gondii. Our genome-wide investigations reveal a specific mechanism of resistance to N-benzoyl-2-hydroxybenzamides mediated by adaptin-3β, a large protein from the secretory protein complex. N-Benzoyl-2-hydroxybenzamide-resistant clones have alterations of their secretory pathway, which traffics proteins to micronemes, rhoptries, dense granules, and acidocalcisomes/plant-like vacuole (PLVs). N-Benzoyl-2-hydroxybenzamide treatment also alters micronemes, rhoptries, the contents of dense granules, and, most markedly, acidocalcisomes/PLVs. Furthermore, QQ-437 is active against chloroquine- resistant Plasmodium falciparum. Our studies reveal a novel class of compounds that disrupts a unique secretory pathway of T. gondii, with the potential to be used as scaffolds in the search for improved compounds to treat the devastating diseases caused by apicomplexan parasites. Copyright
- Fomovska, Alina,Huang, Qingqing,El Bissati, Kamal,Mui, Ernest J.,Witola, William H.,Cheng, Gang,Zhou, Ying,Sommerville, Caroline,Roberts, Craig W.,Bettis, Sam,Prigge, Sean T.,Afanador, Gustavo A.,Hickman, Mark R.,Lee, Patty J.,Leed, Susan E.,Auschwitz, Jennifer M.,Pieroni, Marco,Stec, Jozef,Muench, Stephen P.,Rice, David W.,Kozikowski, Alan P.,McLeod, Rima
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experimental part
p. 2666 - 2682
(2012/08/27)
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- Novel N-dealkylation of N-alkyl sulfonamides and N,N-dialkyl sulfonamides with periodic acid catalyzed by chromium(III) acetate hydroxide
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Chromium(III) acetate hydroxide has been found to be an efficient catalyst for N-dealkylation of N-alkyl sulfonamides and N,N-dialkyl sulfonamides to furnish sulfonamides in good to excellent yields with periodic acid in acetonitrile at room temperature.
- Xu, Liang,Zhang, Suhong,Trudell, Mark L.
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p. 1901 - 1904
(2007/10/03)
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- Carboxylic acids and acylsulfonamides, compositions containing such compounds and methods of treatment
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Compounds of formula I: as well as pharmaceutically acceptable salts, hydrates and esters thereof, are disclosed. The compounds are useful for treating or preventing prostaglandin mediated diseases. Pharmaceutical compositions containing such compounds and methods of treatment are also included.
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