(Z)-(1S,4R,6S,18R)-18-ethoxymethoxy-14-(4-methoxybenzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester | 922732-17-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (Z)-(1S,4R,6S,18R)-18-ethoxymethoxy-14-(4-methoxybenzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester
• 英文别名: ethyl (1S,4R,6S,7Z,18R)-18-(ethoxymethoxy)-14-[(4-methoxyphenyl)methyl]-2,15-dioxo-3,14,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylate
• CAS: 922732-17-0
• 化学式: C₃₀H₄₃N₃O₇
• 分子量: 557.687
• InChiKey: CPUTYDGBIGQACI-MGYXXZTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-(1S,4R,6S,18R)-18-ethoxymethoxy-14-(4-methoxybenzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester 在 lithium hydroxide 、 水 、 柠檬酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 3.5h， 以100%的产率得到(Z)-(1S,4R,6S,18R)-18-ethoxymethoxy-14-(4-methoxybenzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid
  参考文献：
  名称：

  WO2008/96001

  摘要：

  公开号：
• 作为产物：
  描述：

  (Z)-(1S,4R,6S,18R)-18-hydroxy-14-(4-methoxybenzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester 、 氯甲基乙醚 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以53%的产率得到(Z)-(1S,4R,6S,18R)-18-ethoxymethoxy-14-(4-methoxybenzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester
  参考文献：
  名称：

  WO2007/14923

  摘要：

  公开号：

文献信息

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

  公开号：US20090247512A1

  公开（公告）日：2009-10-01

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, or 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 1 is —OR 6 , —NH—SO 2 R 7 ; 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, or C 3-7 cycloalkyl; n is 3, 4, 5, or 6; R 4 and R 5 taken together with the nitrogen atom to which they are attached form a bicyclic ring system selected from wherein said ring system may optionally be substituted with 1-3 substituents; R 6 is hydrogen; aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; R 7 is aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; aryl is phenyl or naphthyl, each of which may be optionally substituted with 1-3 substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from N, O or S, and being optionally substituted with 1-3 substituents pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

  HCV复制抑制剂的公式（I）及其N-氧化物，盐或立体异构体，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；R1为—OR6，—NH—SO2R7；R2为氢，其中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烷基或C3-7环烷基；n为3、4、5或6；R4和R5与它们所连接的氮原子共同形成选自下列的双环系统，其中所述环系统可以选择性地被1-3个取代基取代；R6为氢；芳基；Het；C3-7环烷基，可选地取代C1-6烷基；或C1-6烷基，可选地取代C3-7环烷基，芳基或与Het取代基；R7为芳基；Het；C3-7环烷基，可选地取代C1-6烷基；或C1-6烷基，可选地取代C3-7环烷基，芳基或与Het取代基；芳基为苯基或萘基，每个都可以选择性地被1-3个取代基取代；Het是一个含有1-4个杂原子的5或6元饱和、部分不饱和或完全不饱和的杂环，每个杂原子独立地选自N、O或S，并且可以选择性地被1-3个取代基取代。本发明还提供含有化合物（I）的制药组合物和制备化合物（I）的方法。公式（I）的HCV抑制剂与利托那韦的生物利用度组合也提供。
• HCV INHIBITING MACROCYCLIC PHENYLCARBAMATES
  申请人：Antonov Dmitry

  公开号：US20100041728A1

  公开（公告）日：2010-02-18

  Compounds of the formula 1: including a stereoisomer thereof, or an N-oxide, a pharmaceutically acceptable addition salt, or a pharmaceutically acceptable addition solvate thereof; useful as HCV inhibitors; processes for preparing these compounds as well as pharmaceutical compositions comprising these compounds as active ingredient.

  化合物1的配方，包括其立体异构体，或N-氧化物，药学上可接受的加成盐，或药学上可接受的加成溶剂；作为HCV抑制剂有用；制备这些化合物的过程以及包含这些化合物作为活性成分的制药组合物。
• Macrocylic Inhibitors of Hepatitis C Virus
  申请人：Simmen Kenneth Alan

  公开号：US20090105302A1

  公开（公告）日：2009-04-23

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, or stereoisomers thereof, wherein each dashed line (represented by - - - - -) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1 is —OR 6 , —NH—SO 2 R 7 ; 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, or C 3-7 cycloalkyl; n is 3, 4, 5, or 6; R 4 and R 5 independently from one another are hydrogen, halo, hydroxy, nitro, cyano, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxy-carbonyl, amino, azido, mercapto, C 1-6 alkylthio, polyhaloC 1-6 alkyl, aryl or Het; W is aryl or Het; R 6 is hydrogen; aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; R 7 is aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; aryl is phenyl or naphthyl, each optionally substituted with 1-3 substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1-4 heteroatoms each independently selected from N, O or S, and optionally substituted with 1-3 substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

  HCV复制抑制剂的公式(I)及其N-氧化物、盐或立体异构体，其中每个虚线（由- - - - -表示）表示可选的双键；X为N、CH，其中X带有双键时为C；R1为—OR6、—NH—SO2R7；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烷基或C3-7环烷基；n为3、4、5或6；R4和R5相互独立，为氢、卤素、羟基、硝基、氰基、羧基、C1-6烷基、C1-6烷氧基、C1-6烷氧基C1-6烷基、C1-6烷基羰基、C1-6烷氧羰基、氨基、偶氮基、巯基、C1-6烷基硫基、多卤素C1-6烷基、芳基或杂环基；W为芳基或杂环基；R6为氢、芳基、杂环基、C3-7环烷基，可选地被C1-6烷基取代；或C1-6烷基，可选地被C3-7环烷基、芳基或杂环基取代；R7为芳基、杂环基、C3-7环烷基，可选地被C1-6烷基取代；或C1-6烷基，可选地被C3-7环烷基、芳基或杂环基取代；芳基为苯基或萘基，每个可选地取代1-3个取代基；杂环基为含有1-4个杂原子的5或6元饱和、部分不饱和或完全不饱和的杂环，每个独立选择自N、O或S，并可选地取代1-3个取代基；包含化合物(I)的制药组合物和制备化合物(I)的方法。还提供了公式(I)的HCV抑制剂与利托那韦的生物利用度组合。
• WO2007/14922
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/14923
  申请人：——

  公开号：——

  公开（公告）日：——