methyl (1R,2S)-1-[[(2S,4R)-4-[2-(2-bromoacetyl)-7-methoxy-8-methylquinolin-4-yl]oxy-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate | 801282-45-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (1R,2S)-1-[[(2S,4R)-4-[2-(2-bromoacetyl)-7-methoxy-8-methylquinolin-4-yl]oxy-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate
• CAS: 801282-45-1
• 化学式: C₃₇H₄₇BrN₄O₉
• 分子量: 771.706
• InChiKey: XSSAIPGGAUJNGI-CSGIZIPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  51
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl (1R,2S)-1-[[(2S,4R)-4-[2-(2-bromoacetyl)-7-methoxy-8-methylquinolin-4-yl]oxy-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate 、 N-(氨基硫代甲酰)丙酰胺 以 异丙醇 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Discovery of a Potent and Selective Noncovalent Linear Inhibitor of the Hepatitis C Virus NS3 Protease (BI 201335)

  摘要：

  C-Terminal carboxylic acid containing inhibitors of the NS3 protease are reported. A novel series of linear tripeptide inhibitors that are very potent and selective against the NS3 protease are described. A substantial contribution to the potency of these linear inhibitors arises from the introduction of a C8 substituent on the B-ring of the quinoline moiety found on the P2 of these inhibitors. The introduction of a CS methyl group results not only in a modest increase in the cell-based potency of these inhibitors but more importantly in a much better pharmacokinetic profile in rats as well. Exploration of C8-substitutions led to the identification of the bromo derivative as the best group at this position, resulting in a significant increase in the cell-based potency of this class of inhibitors. Structure activity studies on the C8-bromo derivatives ultimately led to the discovery of clinical candidate 29 (BI 201335), a very potent and selective inhibitor of genotypel NS3 protease with a promising PK profile in rats.

  DOI：

  10.1021/jm100690x
• 作为产物：
  描述：

  methyl (1R,2S)-1-[[(2S,4R)-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]-4-[2-[(2Z)-2-diazoacetyl]-7-methoxy-8-methylquinolin-4-yl]oxypyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate 在 氢溴酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.25h， 以89%的产率得到methyl (1R,2S)-1-[[(2S,4R)-4-[2-(2-bromoacetyl)-7-methoxy-8-methylquinolin-4-yl]oxy-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate
  参考文献：
  名称：

  [EN] HEPATITIS C INHIBITOR COMPOUNDS
  [FR] COMPOSES INHIBITEURS DE L'HEPATITE C

  摘要：

  公式（I）的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如本文所述。这些化合物可用作丙型肝炎病毒NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。

  公开号：

  WO2004103996A1

文献信息

• [EN] HEPATITIS C INHIBITOR COMPOUNDS<br/>[FR] COMPOSES INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004103996A1

  公开（公告）日：2004-12-02

  Compounds of formula (I): wherein B, X, R3, L0, L1, L2, R2, R1 and RC are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  公式（I）的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如本文所述。这些化合物可用作丙型肝炎病毒NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Hepatitis C Inhibitor Compounds
  申请人：LLINAS-BRUNET Montse

  公开号：US20070243166A1

  公开（公告）日：2007-10-18

  Compounds of formula (I): wherein B, X, R 3 , L 0 , L 1 , L 2 , R 2 , R 1 and R C are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  式(I)的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如下。该化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• US7585845B2
  申请人：——

  公开号：US7585845B2

  公开（公告）日：2009-09-08
• US7939667B2
  申请人：——

  公开号：US7939667B2

  公开（公告）日：2011-05-10
• Discovery of a Potent and Selective Noncovalent Linear Inhibitor of the Hepatitis C Virus NS3 Protease (BI 201335)
  作者：Montse Llinàs-Brunet、Murray D. Bailey、Nathalie Goudreau、Punit K. Bhardwaj、Josée Bordeleau、Michael Bös、Yves Bousquet、Michael G. Cordingley、Jiamin Duan、Pat Forgione、Michel Garneau、Elise Ghiro、Vida Gorys、Sylvie Goulet、Ted Halmos、Stephen H. Kawai、Julie Naud、Marc-André Poupart、Peter W. White

  DOI：10.1021/jm100690x

  日期：2010.9.9

  C-Terminal carboxylic acid containing inhibitors of the NS3 protease are reported. A novel series of linear tripeptide inhibitors that are very potent and selective against the NS3 protease are described. A substantial contribution to the potency of these linear inhibitors arises from the introduction of a C8 substituent on the B-ring of the quinoline moiety found on the P2 of these inhibitors. The introduction of a CS methyl group results not only in a modest increase in the cell-based potency of these inhibitors but more importantly in a much better pharmacokinetic profile in rats as well. Exploration of C8-substitutions led to the identification of the bromo derivative as the best group at this position, resulting in a significant increase in the cell-based potency of this class of inhibitors. Structure activity studies on the C8-bromo derivatives ultimately led to the discovery of clinical candidate 29 (BI 201335), a very potent and selective inhibitor of genotypel NS3 protease with a promising PK profile in rats.