57203-01-7Relevant articles and documents
The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist
Moir, Michael,Lane, Samuel,Montgomery, Andrew P.,Hibbs, David,Connor, Mark,Kassiou, Michael
, (2020/12/21)
The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.
Site- And enantiodifferentiating C(sp3)-H oxidation enables asymmetric access to structurally and stereochemically diverse saturated cyclic ethers
Liu, Lei,Sun, Shutao,Yang, Yiying,Zhang, Dongju,Zhao, Ran
supporting information, p. 19346 - 19353 (2020/12/01)
A manganese-catalyzed site- and enantiodifferentiating oxidation of C(sp3)-H bonds in saturated cyclic ethers has been described. The mild and practical method is applicable to a range of tetrahydrofurans, tetrahydropyrans, and medium-sized cyclic ethers with multiple stereocenters and diverse substituent patterns in high efficiency with extremely efficient site- and enantiodiscrimination. Late-stage application in complex biological active molecules was further demonstrated. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity. The ability to employ ether substrates as the limiting reagent, together with a broad substrate scope, and a high level of chiral recognition, represent a valuable demonstration of the utility of asymmetric C(sp3)-H oxidation in complex molecule synthesis.
COMPOUNDS AND THEIR METHODS OF USE
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Page/Page column 149, (2018/09/08)
The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.