Chiral Separation of Manidipine Enantiomers and the Pharmacodynamics of the Hydrochlorides / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the chiral separation of the manidipine enantiomers by the proposed synthetic route, and the blood pressure effect of the hydrochlorides. METHODS: Based on the solubility differences of the salts which are the reaction products of the manidipine enantiomers and the different chiral resolution agents[(+)-Di-p-toluoyl-D-tartaric acid/(-)-Di-p-toluoyl-L-tartaric acid] in the specific solvents, the S and R manidipine enantiomers were obtained respectively, which is called the chemical salting out crystal method. The changes of systolic pressure, diastolic pressure, and mean arterial pressure of spontaneously hypertensive rats(SHR) before and after manidipine hydrochloride medications administration were monitored through implantable physiological signal remote sensing pressure monitoring system (data science international, DSI). RESULTS: The chiral separation process is simple, maneuverability is strong and the ee values and purity of the S and R enantiomorphism isomers are both higher in the synthetic route; in the SHR model, the antihypertensive effect was equivalent between manidipine hydrochloride group and S-manidipine hydrochloride group; R-manidipine hydrochloride did not have the antihypertensive effect. CONCLUSION: The chiral resolution of manidipine enantiomers has certain scientific value, which can improve the efficacy and safety of drug, and which is of great significance to develop manidipine single enantiomeric new drugs.