CAS: 155974-00-8; Ivabradine

该化合物是一种选择性的降低心率的低温剂,主要用于治疗某些心血管疾病,特别是慢性稳定的心血管炎和心脏衰竭,其作用是抑制超极-热活性循环核素固化(HCN)渠道,特别是HCN4渠道,该渠道降低心率,但不会显著影响心肌梗塞或血压.伊瓦布拉迪因具有独特的行动机制的特点,将其与传统的乙型阻塞者区分开来.该物质一般是口服的,吸收得很好,生物利用率可能受食物摄入的影响.其药用动力涉及广泛的肝细胞代谢,主要通过细胞色素P450酶,导致各种代谢物.伊瓦布拉迪因的功效往往通过临床试验来评估,表明其有能力提高锻炼耐受力和降低脑炎袭击的频率.常见副作用包括胸腔,视觉干扰和与其他药物的潜在相互作用.

结构式图片

MSDS等安全信息

    上下游产品

    CAS号866783-12-2 (S)-(4,5-dimeth... | CAS号85175-82-2 3-(7,8-dimethox... | CAS号1086026-31-4 3-[3-[[[(7S)-3,... | CAS号20925-64-8 7,8-二甲氧基-1,3,4,... | CAS号1031767-71-1 3-chloro-N-{[(7... | CAS号120-20-7 3,4-二甲氧基苯乙胺 | CAS号148849-67-6 盐酸伊伐布雷定 | CAS号1086026-42-7 3-{3-[((S)-3,4-... | CAS号148849-67-6 盐酸伊伐布雷定

    合成工艺路线路线简述

    • 合成目标产物 Ivabradine 主要起始原料 3-[3-[[[(7S)-3,4-Dimethoxybicyclo[4.2.0]Octa-1,3,5-Trien-7-Yl]Methyl]Methylamino]Propyl]-1,3-Dihydro-7,8-Dimethoxy-H-3-Benzazepin-2-One
    • (文献来源)合成步骤主要原料 3-[3-[[[(7S)-3,4-Dimethoxybicyclo[4.2.0]Octa-1,3,5-Trien-7-Yl]Methyl]Methylamino]Propyl]-1,3-Dihydro-7,8-Dimethoxy-H-3-Benzazepin-2-One
    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.

    海关参考信息

    专利信息


    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.
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    主要参考文献


    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.
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