盐酸伊伐布雷定置于sodium Hydroxide体系中,用 水 用作溶剂,化学反应 0.17H,以95%的收率获得伊伐布雷定 参考文献: New Salt Of Ivabradine And Uses Thereof[fr] Nouveau Sel D'Ivabradine Et Utilisations De Ce Dernier 标题: New Salt Of Ivabradine And Uses Thereof[fr] Nouveau Sel D'Ivabradine Et Utilisations De Ce Dernier 摘要:本发明涉及伊维布地嗪的新型盐和物理形式,其形成方法以及用途,例如用于治疗心肌缺血等.
专利号:US-9506095-B2 优先权日:2012-02-09 标 题:Process for the enzymatic synthesis of (7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid or esters thereof, and application in the synthesis of ivabradine and salts thereof 发明人:PEDRAGOSA-MOREAU SANDRINE; LEFOULON FRANÇOIS 权利人:SERVIER LAB; LES LABORATORIES SERVIER 摘要:Process for the enzymatic synthesis of the compound of formula (I): n nwherein R 1 represents a hydrogen atom or an alkyl group.n n Application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid.
专利号:US-7928223-B2 优先权日:2008-06-20 标题:Process for the synthesis of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one, and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid 发明人:LERESTIF JEAN-MICHEL; LECOUVE JEAN-PIERRE; BRIGOT DANIEL 权利人:SERVIER LAB 摘要:Process for the synthesis of the compound of formula (I): n n n n n n n n n n Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.
专利号:US-9045788-B2 优先权日:2012-07-17 标题:Process for the enzymatic synthesis of (7S)-1-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl) N-methyl methanamine, and application in the synthesis of ivabradine and salts thereof 发明人:PEDRAGOSA-MOREAU SANDRINE; LEFOULON FRANÇOIS; MORIS VARAS FRANCISCO; GONZALEZ SABIN JAVIER 权利人:SERVIER LAB 摘要:Process for the enzymatic synthesis of the compound of formula (I), (7S)-1-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl)N-methyl methanamine: n nand application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid.
专利号:US-8927708-B2 优先权日:2013-03-26 标 题 :Process for the synthesis of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one compounds, and application in the synthesis of ivabradine 发明人:LE FLOHIC ALEXANDRE 权利人:SERVIER LAB 摘要:Process for the synthesis of the compound of formula (I): n nwherein R represents a para-methoxybenzyl (PMB) group or the following group:n n nApplication in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid.
专利号:US-9476071-B2 优先权日:2013-02-28 标 题 :Process for the enzymatic synthesis of (7S)-3,4-dimethoxybicyclo[4.2.0]OCTA-1,3,5-triene-7-carboxylic acid and application in the synthesis of ivabradine and salts thereof 发明人:PEDRAGOSA-MOREAU SANDRINE; LEFOULON FRANÇOIS 权利人:SERVIER LAB 摘要:Process for the enzymatic synthesis of the compound of formula (I): n ncomprising enantioselective enzymatic hydrolysis of the nitrile of formula (IV):n n nusing the nitrilase of Rhodococcus rhodochrous of EMBL accession number EF467367.1, and the application of such a process in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid.
专利号:US-8779122-B2 优先权日:2012-11-08 标 题:Process for the synthesis of (2E)-3-(3,4-dimethoxyphenyl)prop-2-enenitrile, and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid 发明人:CARRANZA MARIA DEL PILAR; GARCIA ARANDA MARIA ISABEL; GONZALEZ JOSÉ LORENZO; SANCHEZ FRÉDÉRIC 权利人:SERVIER LAB 摘要:Process for the synthesis of the compound of formula (I): n nApplication in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid and hydrates thereof.
1: Ide T, Ohtani K, Higo T, Tanaka M, Kawasaki Y, Tsutsui H. Ivabradine for the Treatment of Cardiovascular Diseases. Circ J. 2019 Jan 25;83(2):252-260. doi: 10.1253/circj.CJ-18-1184. Epub 2018 Dec 29. 18(5):393-402. doi: 10.1080/14740338.2019.1612873. Epub 2019 May 10. 243:167-175. doi: 10.1007/164_2016_55. 70(14):1777-1784. doi: 10.1016/j.jacc.2017.08.038. 6(5):1088-1091. doi: 10.1002/ehf2.12499. Epub 2019 Jul 23. 6: Dallapellegrina L, Sciatti E, Vizzardi E. Ivabradine and endothelium: an update. Ther Adv Cardiovasc Dis. 2020 Jan-Dec;14:1753944720934937. doi: 10.1177/1753944720934937.
合成参考文献
摘要:Mach F. [Reducing heart rate to treat angina pectoris]. Rev Med Suisse. 2011 Jun 08;7(298):1276–80. 摘要:Heart failure: ivabradine is no better than optimised beta-blocker therapy. Prescrire Int. 2011 Jul;20(118):189–90. 参考文献:10.1016/j.ijcard.2011.06.098 摘要:Volterrani M, Cice G, Caminiti G, Vitale C, D'Isa S, Perrone Filardi P, Acquistapace F, Marazzi G, Fini M, Rosano GMC. Effect of Carvedilol, Ivabradine or their combination on exercise capacity in patients with Heart Failure (the CARVIVA HF trial). International Journal of Cardiology. 2011 Sep;151(2):218–24. doi: 10.1016/j.ijcard.2011.06.098. 参考文献:10.1007/s00210-011-0664-4 摘要:Goegelein H, Gautier P, Roccon A, O'Connor S, Ruetten H. Effects of the novel amiodarone-like compound SAR114646A on cardiac ion channels and ventricular arrhythmias in rats. Naunyn Schmiedebergs Arch Pharmacol. 2011 Sep;384(3):231–44. doi: 10.1007/s00210-011-0664-4. 参考文献:10.2174/092986711796642427 摘要:Koncz I, Szél T, Jaeger K, Baczkó I, Cerbai E, Romanelli MN, Gy Papp J, Varró A. Selective pharmacological inhibition of the pacemaker channel isoforms (HCN1-4) as new possible therapeutical targets. Curr Med Chem. 2011;18(24):3662–74. doi: 10.2174/092986711796642427.