3,4-Dihydro-1H-isoquinoline-2-carboxylic acid (3R,5S)-5-(1-cyclopropylaminooxalyl-butylcarbamoyl)-1-{(S)-2-[(S)-2-(5-methoxycarbonyl-pentanoylamino)-3-methyl-butyrylamino]-3-methyl-butyryl}-pyrrolidin-3-yl ester | 402957-78-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 3,4-Dihydro-1H-isoquinoline-2-carboxylic acid (3R,5S)-5-(1-cyclopropylaminooxalyl-butylcarbamoyl)-1-{(S)-2-[(S)-2-(5-methoxycarbonyl-pentanoylamino)-3-methyl-butyrylamino]-3-methyl-butyryl}-pyrrolidin-3-yl ester
• 英文别名: L-prolinamide, N-(6-methoxy-1,6-dioxohexyl)-L-valyl-L-valyl-N-[1-[2-(cyclopropylamino)-1,2-dioxoethyl]butyl]-4-[[(3,4-dihydro-2(1H)-isoquinolinyl)carbonyl]oxy]-, (4R)-；[(3R,5S)-5-[[1-(cyclopropylamino)-1,2-dioxohexan-3-yl]carbamoyl]-1-[(2S)-2-[[(2S)-2-[(6-methoxy-6-oxohexanoyl)amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]pyrrolidin-3-yl] 3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 402957-78-2
• 化学式: C₄₁H₆₀N₆O₁₀
• 分子量: 796.962
• InChiKey: LFMBRHPFQYZPEC-MIIJRMAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  57
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  210
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3,4-Dihydro-1H-isoquinoline-2-carboxylic acid (3R,5S)-5-(1-cyclopropylaminooxalyl-butylcarbamoyl)-1-{(S)-2-[(S)-2-(5-methoxycarbonyl-pentanoylamino)-3-methyl-butyrylamino]-3-methyl-butyryl}-pyrrolidin-3-yl ester 生成 3,4-Dihydro-1H-isoquinoline-2-carboxylic acid (3R,5S)-1-{(S)-2-[(S)-2-(5-carboxy-pentanoylamino)-3-methyl-butyrylamino]-3-methyl-butyryl}-5-(1-cyclopropylaminooxalyl-butylcarbamoyl)-pyrrolidin-3-yl ester
  参考文献：
  名称：

  P4 cap modified tetrapeptidyl α-ketoamides as potent HCV NS3 protease inhibitors

  摘要：

  We describe herein the design, syntheses, and biological evaluation of new series of P4 tetrazole and adipic acid, ester, amide capped tetrapeptidyl alpha-ketoamide based HCV protease inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.078
• 作为产物：
  描述：

  脂肪酸甲酯 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 3,4-Dihydro-1H-isoquinoline-2-carboxylic acid (3R,5S)-5-(1-cyclopropylaminooxalyl-butylcarbamoyl)-1-{(S)-2-[(S)-2-(5-methoxycarbonyl-pentanoylamino)-3-methyl-butyrylamino]-3-methyl-butyryl}-pyrrolidin-3-yl ester
  参考文献：
  名称：

  P4 cap modified tetrapeptidyl α-ketoamides as potent HCV NS3 protease inhibitors

  摘要：

  We describe herein the design, syntheses, and biological evaluation of new series of P4 tetrazole and adipic acid, ester, amide capped tetrapeptidyl alpha-ketoamide based HCV protease inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.078

文献信息

• Peptidomimetic protease inhibitors
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2368878A1

  公开（公告）日：2011-09-28

  The present invention relates to peptidomimetic compounds useful as protease inhibitors (1), particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，用作蛋白酶抑制剂（1），特别是丝氨酸蛋白酶抑制剂，更特别是丙型肝炎NS3蛋白酶抑制剂；中间体；它们的制备，包括到中间体的新型立体选择性过程。本发明还涉及制药组合物和使用这些化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，并使用这些组合物治疗或预防患者的HCV感染的方法。本发明还涉及用于治疗或预防患者的HCV感染的套件或药物包。
• PEPTIDOMIMETIC PROTEASE INHIBITORS
  申请人：BABINE ROBERT EDWARD

  公开号：US20120282219A1

  公开（公告）日：2012-11-08

  The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel stereoselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，作为蛋白酶抑制剂，特别是作为丝氨酸蛋白酶抑制剂，更特别是作为丙型肝炎NS3蛋白酶抑制剂；以及其中间体；它们的制备，包括新的对中间体的立体选择性过程。本发明还涉及制药组合物，以及使用这些化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，并使用这些组合物来治疗或预防患者的HCV感染。本发明还涉及用于治疗或预防患者HCV感染的工具包或药物包。
• Chiral intermediates for the preparation of peptidomimetic protease inhibitors
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2368877A1

  公开（公告）日：2011-09-28

  The present invention relates to peptidomimetic compounds useful as protease inhibitors (1), particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及可用作蛋白酶抑制剂（1），特别是丝氨酸蛋白酶抑制剂，更特别是丙型肝炎 NS3 蛋白酶抑制剂的拟肽化合物；其中间体；其制备方法，包括制备中间体的新型立体选择性工艺。本发明还涉及药物组合物以及使用这些化合物抑制 HCV 蛋白酶或治疗 HCV 感染患者或与感染相关的生理状况的方法。本发明还提供了药物组合物，除一种或多种HCV丝氨酸蛋白酶抑制剂外，还包括一种或多种具有抗HCV活性的干扰素和/或一种或多种具有抗HCV活性的化合物和药学上可接受的载体，以及使用该组合物治疗或预防患者HCV感染的方法。本发明还涉及一种用于治疗或预防患者HCV感染的试剂盒或药包。
• US8529882B2
  申请人：——

  公开号：US8529882B2

  公开（公告）日：2013-09-10
• P4 cap modified tetrapeptidyl α-ketoamides as potent HCV NS3 protease inhibitors
  作者：David X Sun、Lifei Liu、Beverly Heinz、Alexander Kolykhalov、Jason Lamar、Robert B Johnson、Q.May Wang、Yvonne Yip、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2004.05.078

  日期：2004.8

  We describe herein the design, syntheses, and biological evaluation of new series of P4 tetrazole and adipic acid, ester, amide capped tetrapeptidyl alpha-ketoamide based HCV protease inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.