124578-19-4Relevant articles and documents
Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts
Le Manach, Claire,Dam, Jean,Woodland, John G.,Kaur, Gurminder,Khonde, Lutete P.,Brunschwig, Christel,Njoroge, Mathew,Wicht, Kathryn J.,Horatscheck, André,Paquet, Tanya,Boyle, Grant A.,Gibhard, Liezl,Taylor, Dale,Lawrence, Nina,Yeo, Tomas,Mok, Sachel,Eastman, Richard T.,Dorjsuren, Dorjbal,Talley, Daniel C.,Guo, Hui,Simeonov, Anton,Reader, Janette,Van Der Watt, Mari?tte,Erlank, Erica,Venter, Nelius,Zawada, Jacek W.,Aswat, Ayesha,Nardini, Luisa,Coetzer, Theresa L.,Lauterbach, Sonja B.,Bezuidenhout, Belinda C.,Theron, Anjo,Mancama, Dalu,Koekemoer, Lizette L.,Birkholtz, Lyn-Marie,Wittlin, Sergio,Delves, Michael,Ottilie, Sabine,Winzeler, Elizabeth A.,Smith, Dennis,Fidock, David A.,Street, Leslie J.,Basarab, Gregory S.,Duffy, James,Chibale, Kelly
supporting information, p. 2291 - 2309 (2021/03/01)
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.
Lipase-catalyzed hydrolysis of 2-(4-hydroxyphenyl)propionic acid ethyl ester to (R)-(?)-2-(4-hydroxyphenyl)propanoic acid
Yuan, Xin,Zhang, Panliang,Liu, Guangyong,Xu, Weifeng,Tang, Kewen
, p. 2461 - 2468 (2019/07/16)
Stereoselective hydrolysis of (±)-2-(4-hydroxyphenyl)propionic acid ethyl ester (2-HPPAEE) by lipase catalyzed in aqueous system was investigated. Lipase AK with higher catalytic activity and enantioselectivity was selected as catalyst. Simultaneously, factors affecting the conversion of substrate (c) and the enantiomeric excess of product (eep) were optimized. The optimal conditions were established, involving 45?°C of temperature, 5.5 of pH, 10?mg of lipase AK dosage, 0.04?mmol of substrate dosage and 40?h of reaction time. Under the optimum conditions, c and eep could reach up to 49% and 98%, respectively.
PROPIONIC ACID DERIVATIVE
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, (2008/06/13)
A propionic acid derivative represented by general formula (I) or a pharmaceutically acceptable acid-addition salt thereof, wherein A represents OH, C1-C8 lower alkoxy, -NR1R2, or C1-C8 lower alkoxy which may be substituted by halogen, optionally susbtitu