| 摘要 |
PURPOSE: Ivabradine and additional salts of pharmaceutically acceptable acids thereof are provided to show superior pharmacological and therapeutic characteristics, especially bradycardia and to treat various diseases and heart failure. CONSTITUTION: A method for synthesizing ivabradine of chemical formula I comprises the steps of: performing lactamization reaction of a compound of chemical formula VI in an organic solvent under the presence of a coupling agent and a base to prepare ivabradine of chemical formula I; and converting ivabradine into addition salts of pharmaceutically acceptable acids or a hydrate thereof. The pharmaceutically acceptable acid is selected among hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulfonic acid, benzenesulfonic acid, and camporic acid of ivabradine. The coupling agent is thionyl chloride. |
