van Veldhoven, Jacobus P. D.; Campostrini, Giulia; van Gessel, Constantijn J. E.; Ward-van Oostwaard, Dorien; Liu, Rongfang; Mummery, Christine L.; Bellin, Milena; IJzerman, Adriaan P. published an article on February 15 ,2021. The article was titled 《Targeting the Kv11.1 (hERG) channel with allosteric modulators. Synthesis and biological evaluation of three novel series of LUF7346 derivatives》, and you may find the article in European Journal of Medicinal Chemistry.Computed Properties of C6H8N2 The information in the text is summarized as follows:
Three novel series of substituted benzophenones for their allosteric modulation of the human Kv11.1 (hERG) channel were synthesized and evaluated. Effects of this is compared with reference compound LUF7346 previously shown to shorten the action potential of cardiomyocytes derived from human stem cells. Most compounds behaved as neg. allosteric modulators (NAMs) of [3H]dofetilide binding to the channel. Compound III [R = 2-Cl; R1 = CH2cPr; X= Y = C] was the most potent amongst all ligands, remarkably reducing the affinity of dofetilide in competitive displacement assays. One of the other II [R = H; X = N] tested in a second radioligand binding set-up, displayed unusual displacement characteristics with a pseudo-Hill coefficient significantly distinct from unity, further indicative of its allosteric effects on the channel. Some compounds were evaluated in a more physiol. relevant context in beating cardiomyocytes derived from human induced pluripotent stem cells. Surprisingly, the compounds tested showed effects quite different from the reference NAM LUF7346. For instance, compound I [R = 3-Me] prolonged, rather than shortened, the field potential duration, while it did not influence this parameter when the field potential was already prolonged by dofetilide. In subsequent patch clamp studies on HEK293 cells expressing the hERG channel the compounds behaved as channel blockers. In conclusion, new allosteric modulators of the hERG channel were successfully synthesized and identified . Unexpectedly, their effects differed from the reference compound in functional assays on hERG-HEK293 cells and human cardiomyocytes, to the extent that the compounds behaved as stand-alone channel blockers.4-Amino-2-picoline(cas: 18437-58-6Computed Properties of C6H8N2) was used in this study.
4-Amino-2-picoline(cas: 18437-58-6) belongs to anime. Amines characteristically form salts with acids; a hydrogen ion, H+, adds to the nitrogen. With the strong mineral acids (e.g., H2SO4, HNO3, and HCl), the reaction is vigorous. Salt formation is instantly reversed by strong bases such as NaOH. Neutral electrophiles (compounds attracted to regions of negative charge) also react with amines; alkyl halides (R′X) and analogous alkylating agents are important examples of electrophilic reagents.Computed Properties of C6H8N2