Mosapride(KOREA UNITED PHARM, Inc.)

Aryl fluorosulfates of varying complexities have been used in amination reactions in water using a new Pd oxidative addition complex (OAC‐1) developed specifically to match the needs of the fine chemicals industry, not only in terms of functional group tolerance, but also reflecting time considerations associated with these important C−N couplings. Also especially noteworthy is that they replace both PFAS‐related triflates and nonaflates, which are today out of favor due to recent government regulations. The new complex based on the BippyPhos ligand is used at low loadings and under aqueous micellar conditions. Moreover, it is easily prepared and stable to long term storage. DFT calculations on the OAC precatalyst compare well with the X‐ray structure of the crystals with π‐complexation to the aromatic system of the ligand and also confirm the NMR data showing a mixture of conformers in solution that differ from the X‐ray structure in rotation of the phenyl and t‐butyl ligand substituents. An extensive variety of coupling partners, including pharmaceutically relevant APIs, readily participate under mild and environmentally responsible reaction conditions.

Mosapride (4-amino-5-chloro-2-ethoxy-N-[[4-[(4-fluorophenyl) methyl]-2-morpholinyl]-methyl] benzamide) is a potent agonist at gastrointestinal 5-HT4 receptors. Mosapride is an approved drug to treat several gastric diseases. We tested the hypothesis that mosapride also stimulates 5-HT4 receptors in the heart. Mosapride increased the force of contraction and beating rate in isolated atrial preparations from mice with cardiac overexpression of human 5-HT4-serotonin receptors (5-HT4-TG). However, it is inactive in wild-type mouse hearts (WT). Mosapride was less effective and potent than serotonin in raising the force of contraction or the beating rate in 5-HT4-TG. Only in the presence of cilostamide (1 μM), a phosphodiesterase III inhibitor, mosapride, and its primary metabolite time dependently raised the force of contraction under isometric conditions in isolated paced human right atrial preparations (HAP, obtained during open heart surgery). In HAP, mosapride (10 μM) reduced serotonin-induced increases in the force of contraction. Mosapride (10 µM) shifted the concentration–response curves to serotonin in HAP to the right. These data suggest that mosapride is a partial agonist at 5-HT4-serotonin receptors in HAP.