Add time:08/22/2019         Source:sciencedirect.com

The synthesis of S-(−)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride (D140S·HCl 6), a novel short acting β1-specific adrenoceptor antagonist, has been described. The antagonist potency for D140S·HCl 6 has been compared with esmolol, another short acting agent, and other well known β-adrenoceptor antagonists in isolated rat tissue preparations. The pharmacokinetics of D140S·HCl 6 in 7 day continuous intravenous infusions and 4 weeks intravenous bolus injection studies in conscious rats and dogs have been examined in toxicology studies. The effect on the isoprenaline-induced heart rate increase and the pharmacodynamic half-life of D140S·HCl 6 has been compared with esmolol in a conscious rat model. In addition, the results of a range of toxicological studies are presented. The results indicate that D140S·HCl 6 is a highly specific β1-adrenoceptor antagonist (pA2=8.15±0.22, β1/β2 selectivity>4400). The in vitro studies suggest D140S·HCl is ca. ten times more potent and 60 times more β1-specific than racemic esmolol. Pharmacokinetic non-linearity was seen when given as a 7 day intravenous infusion at toxicological doses above 10 mg kg−1 h−1 in the rat and 2.5 mg kg−1 h−1 in the dog. Both D140S·HCl 6 and esmolol have very short durations of action after intravenous infusion in the rat (pharmacodynamic half-life is <15 min for D140S·HCl and 10 min for esmolol). The toxicological tests indicate that D140S·HCl 6 shows no unexpected toxicity and none of the tissue irritancy problems reported for esmolol formulations.

We also recommend Trading Suppliers and Manufacturers of 2-(2-Ethoxyethoxy)ethyl acetate (cas 112-15-2). Pls Click Website Link as below: cas 112-15-2 suppliers