7623-09-8Relevant articles and documents
Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors
Xie, Yiyue,Tummala, Padmaja,Oakley, Aaron J.,Deora, Girdhar Singh,Nakano, Yuji,Rooke, Melissa,Cuellar, Matthew E.,Strasser, Jessica M.,Dahlin, Jayme L.,Walters, Michael A.,Casarotto, Marco G.,Board, Philip G.,Baell, Jonathan B.
, p. 2894 - 2914 (2020/04/08)
Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1β and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the kinact/KI values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine kinact/KI values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.
Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold
Zhu, Xiang,Zhang, Min,Yu, Linhua,Xu, Zhihong,Yang, Dan,Du, Xiaoying,Wu, Qinglai,Li, Junkai
supporting information, p. 2453 - 2460 (2018/03/29)
Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158?mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059?mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.
Terpene Cyclizations inside a Supramolecular Catalyst: Leaving-Group-Controlled Product Selectivity and Mechanistic Studies
Zhang, Qi,Catti, Lorenzo,Pleiss, Jürgen,Tiefenbacher, Konrad
supporting information, p. 11482 - 11492 (2017/08/30)
The tail-to-head terpene cyclization is arguably one of the most complex reactions found in nature. The hydrogen-bond-based resorcinarene capsule represents the first man-made enzyme-like catalyst that is capable of catalyzing this reaction. Based on noncovalent interactions between the capsule and the substrate, the product selectivity can be tuned by using different leaving groups. A detailed mechanistic investigation was performed to elucidate the reaction mechanism. For the cyclization of geranyl acetate, it was found that the cleavage of the leaving group is the rate-determining step. Furthermore, the studies revealed that trace amounts of acid are required as cocatalyst. A series of control experiments demonstrate that a synergistic interplay between the supramolecular capsule and the acid traces is required for catalytic activity.
