Olprinone Hydrochloride Hydrate

Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition.

Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning (IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl).

The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group.

The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

The imidazo[1,2‐a]pyridine scaffold has gained significant attention due to its presence as a lead structure in several commercially available pharmaceuticals like zolimidine, zolpidem, olprinone, soraprazan, etc. Further, indole‐based imidazo[1,2‐a]pyridine derivatives have been found interesting due to their anticancer and antibacterial activities. However, limited methods have been reported for the synthesis of indole‐based imidazo[1,2‐a]pyridines. In this study, we have successfully developed a biocatalytic process for synthesizing indole‐based imidazo[1,2‐a]pyridine derivatives using the α‐amylase enzyme catalyzed Groebke‐Blackburn‐Bienayme (GBB) multicomponent reaction of 2‐aminopyridine, indole‐3‐carboxaldehyde, and isocyanide. The generality and robustness of this protocol were shown by synthesizing differently substituted indole‐based imidazo[1,2‐a]pyridines in good isolated yields. Furthermore, to make α‐amylase a reusable catalyst for GBB multicomponent reaction, it was immobilized onto magnetic metal‐organic framework (MOF) materials [Fe3O4@MIL‐100(Fe)] and found reusable up to four consecutive catalytic cycles without the significant loss in catalytic activity.