Development of Polar Organic Mode Chromatographic Method by Polysaccharide-Based Immobilized Chiral Selector and Validation for the Determination of the Enantiopurity of Novel Mineralocorticoid Receptor Antagonist Atropisomer–Esaxerenone

Atropisomerism in the Pharmaceutically Relevant Realm

“…Recent examples of class-3 atropisomers include BMS’s noncovalent BTK inhibitor BMS-986142 (which possesses a class-3 and a class-2 atropisomeric axis), Astra-Zeneca’s MCL-1 inhibitor AZD-5991, and Mirati’s PRMT5-MTA inhibitor MTRX-1719 . Esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist (MCRA) developed by Daiichi-Sankyo and approved in Japan for the treatment of hypertension, also exists as isolable atropisomers, with one atropisomer possessing the majority of activity. , Unsurprisingly, there are fewer examples of class-2 atropisomers in clinical trials. There are myriad examples of class-1 atropisomers currently in clinical trials, with a few illustrative examples in Figure .…”

“…28 Esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist (MCRA) developed by Daiichi-Sankyo and approved in Japan 29 for the treatment of hypertension, also exists as isolable atropisomers, with one atropisomer possessing the majority of activity. 29,30 There have also been myriad examples of class-3 atropisomers in the recent medicinal chemistry literature (Figure 5). Gilead published a series of papers 31,32 that led to the discovery of a selective PI3Kβ inhibitor that existed as a class-3 atropisomer.…”

“… 28 Esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist (MCRA) developed by Daiichi-Sankyo and approved in Japan 29 for the treatment of hypertension, also exists as isolable atropisomers, with one atropisomer possessing the majority of activity. 29 , 30 Unsurprisingly, there are fewer examples of class-2 atropisomers in clinical trials. There are myriad examples of class-1 atropisomers currently in clinical trials, with a few illustrative examples in Figure 4 .…”