Synthesis of calcium sensitizer levosimendan
|School||Shenyang Pharmaceutical University|
|Keywords||Levosimendan Heart Failure Calcium sensitizer Synthesis Medicinal Chemistry|
This article briefly the pathogenesis of heart failure and drug treatment , described in detail the mechanism of its development overview of the role of the anti-heart failure drug , levosimendan . In reference to the literature on the basis of L-lactic acid as the starting material by esterification , replaced by acid hydrolysis , the Friedel-Crafts acylation , alkylation , hydrolysis , catalytic hydrogenolysis , cyclization and diazotization 12 of step reaction of levosimendan , and its structure was confirmed by mass spectrometry , NMR conclusive evidence of the total yield increased by 0.5 % compared to literature . Meanwhile, 4 , 6 , 8 and 9, the reaction conditions of levosimendan and its important intermediates more detailed research and study , in which 6.5 % Synthesis of Intermediate 4 in yield compared with the literature ; Intermediate 8 the increase in yield compared with literature ; in the intermediates 6 synthesis using cheap nitrobenzene instead of the literature relatively expensive 1,2,4 - trichlorobenzene , 1% increase in yield than reported in the literature , the cost significantly reduced; with inexpensive readily available sodium methoxide instead of sodium hydride, to simplify the operating conditions reported in the literature during the synthesis of the intermediate 9 . Furthermore, in the intermediate 2,6,7 and 11 post-treatment process using recrystallization instead of column chromatography method reported in the literature , to shorten the cycle of operation , simplifies the experimental procedures , reduce production costs and facilitates in large The scale used in the production .