ethyl (1R,2S)-2-ethenyl-1-[[(2S,4R)-1-(hept-6-enylcarbamoyl)-4-[7-methoxy-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate | 922519-96-8

• 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: ethyl (1R,2S)-2-ethenyl-1-[[(2S,4R)-1-(hept-6-enylcarbamoyl)-4-[7-methoxy-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate
• CAS: 922519-96-8
• 化学式: C₃₇H₄₇N₅O₆S
• 分子量: 689.876
• InChiKey: PVCOOZJWUPEMNK-YMBUWOHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  49
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  160
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl (1R,2S)-2-ethenyl-1-[[(2S,4R)-1-(hept-6-enylcarbamoyl)-4-[7-methoxy-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate 在 二氯(邻异丙氧基苯基亚甲基)(三环己基膦)钌 作用下， 以 1,1-二氯乙烷 为溶剂， 反应 16.0h， 以57%的产率得到ethyl (1S,4R,6S,7Z,18R)-18-[7-methoxy-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-2,15-dioxo-3,14,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylate
  参考文献：
  名称：

  WO2007/14925

  摘要：

  公开号：
• 作为产物：
  描述：

  、 6-heptenylamine 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl (1R,2S)-2-ethenyl-1-[[(2S,4R)-1-(hept-6-enylcarbamoyl)-4-[7-methoxy-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxypyrrolidine-2-carbonyl]amino]cyclopropane-1-carboxylate
  参考文献：
  名称：

  WO2007/14925

  摘要：

  公开号：

文献信息

• MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Simmen Kenneth Alan

  公开号：US20090062311A1

  公开（公告）日：2009-03-05

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers thereof, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1a and R 1b are hydrogen, C 3-7 cycloalkyl, aryl, Het, C 1-6 alkoxy, C 1-6 alkyl optionally substituted with halo, C 1-6 alkoxy, cyano, polyhaloC 1-6 alkoxy, C 3-7 cycloalkyl, aryl, or with Het; or R 1a and R 1b together with the nitrogen to which they are attached form a 4 to 6 membered heterocyclic ring which may be optionally substituted; L is a direct bond, —O—, —O—C 1-4 alkanediyl-, —O—CO—, —O—C(═O)—NR 5a — or —O—C(═O)—NR 5a —C 1-4 alkanediyl-; R 2 is hydrogen, and where X is C or CH, R 2 may also be C 1-6 alkyl; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, C 3-7 cycloalkyl, amino, mono- or diC 1-6 alkylamino; R 4 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from O, S and N, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents; and Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S, being optionally condensed with a benzene ring, and wherein Het may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

  公式（I）及其N-氧化物、盐和立体异构体的HCV复制抑制剂，其中每个虚线表示可选的双键；X为N、CH，其中X带有双键时为C；R1a和R1b为氢、C3-7环烷基、芳基、Het、C1-6烷氧基、C1-6烷基（可选用卤代、C1-6烷氧基、氰基、多卤代C1-6烷氧基、C3-7环烷基、芳基或Het取代）、或R1a和R1b与它们所连接的氮一起形成一个4到6成员杂环环，该环可以选择性地被取代；L为直接键，-O-，-O-C1-4烷二基-，-O-CO-，-O-C（═O）-NR5a-或-O-C（═O）-NR5a-C1-4烷二基-；R2为氢，当X为C或CH时，R2也可以是C1-6烷基；R3为氢、C1-6烷基、C1-6烷氧基C1-6烷基、C3-7环烷基、氨基、单取代或二取代C1-6烷基氨基；R4为芳基或饱和、部分不饱和或完全不饱和的5或6成员单环或9到12成员的双环杂环系统，其中所述杂环系统含有一个氮，且可以选择性地含有一个到三个来自O、S和N的其他杂原子，其余环成员为碳原子；其中所述环系统可以选择性地被取代；n为3、4、5或6；p为1或2；芳基为苯基、萘基、茚基或1,2,3,4-四氢萘基，每个都可以选择性地取代一个、两个或三个取代基；Het是一个5或6成员饱和、部分不饱和或完全不饱和的杂环环，其中包含1到4个来自N、O和S的杂原子，可以选择性地与苯环融合，且Het可以选择性地取代一个、两个或三个取代基；含有化合物（I）的制药组合物和制备化合物（I）的方法。
• Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors
  作者：Sandrine Vendeville、Magnus Nilsson、Herman de Kock、Tse-I Lin、Dmitry Antonov、Björn Classon、Susana Ayesa、Vladimir Ivanov、Per-Ola Johansson、Pia Kahnberg、Anders Eneroth、Kristina Wikstrom、Lotta Vrang、Michael Edlund、Stefan Lindström、Wim Van de Vreken、David McGowan、Abdellah Tahri、Lili Hu、Oliver Lenz、Frederic Delouvroy、Marleen Van Dooren、Natalie Kindermans、Dominique Surleraux、Piet Wigerinck、Åsa Rosenquist、Bertil Samuelsson、Kenneth Simmen、Pierre Raboisson

  DOI：10.1016/j.bmcl.2008.10.004

  日期：2008.12

  A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K-i = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 mu M) inhibitor, displaying an excellent PK pro. le in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. (C) 2008 Elsevier Ltd. All rights reserved.
• Macrocylic Inhibitors Of Hepatitis C Virus
  申请人：Simmen Kenneth Alan

  公开号：US20080200503A1

  公开（公告）日：2008-08-21

  Inhibitors of HCV of formula (I). and the N-oxides, salts, and stereoisomers thereof, wherein the dashed line represents an optional double bond between atoms C7 and C8; R 1 is hydrogen or C 1-6 alkyl; R 2 is hydrogen or C 1-6 alkyl; and n is 3, 4, 5, or 6; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I) are provided. Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
• US8008251B2
  申请人：——

  公开号：US8008251B2

  公开（公告）日：2011-08-30
• US8227407B2
  申请人：——

  公开号：US8227407B2

  公开（公告）日：2012-07-24