(2S,4R)-2-((1R,2S)-1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester | 922732-11-4

• 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: (2S,4R)-2-((1R,2S)-1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)pyrrolidine-1-carboxylate；tert-butyl (2S,4R)-2-[[(1R,2S)-2-ethenyl-1-ethoxycarbonylcyclopropyl]carbamoyl]-4-(4-nitrobenzoyl)oxypyrrolidine-1-carboxylate
• CAS: 922732-11-4
• 化学式: C₂₅H₃₁N₃O₉
• 分子量: 517.536
• InChiKey: MFPNGSKEDSSMEI-VDQVMUTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,4R)-2-((1R,2S)-1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-nitrobenzoic acid (3R,5S)-5-((R)-1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl ester
  参考文献：
  名称：

  WO2007/14921

  摘要：

  公开号：
• 作为产物：
  描述：

  4-硝基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.08h， 以56%的产率得到(2S,4R)-2-((1R,2S)-1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2007/14921

  摘要：

  公开号：

文献信息

• Macrocylic Inhibitors of Hepatitis C Virus
  申请人：Simmen Kenneth Alan

  公开号：US20090118312A1

  公开（公告）日：2009-05-07

  Compounds of the formula I: and N-oxides, salts, and stereoisomers thereof wherein A is OR 1 , NHS(═O) p R 2 ; wherein; R 1 is hydrogen, C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkylene-heterocyclyl; R 2 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl; p is independently 1 or 2; n is 3, 4, 5 or 6; — denotes an optional double bond; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; Rq is H or when L is CRz, Rq can also be C 1 -C 6 alkyl; Rr is quinazolinyl, optionally substituted with one two or three substituents each independently selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxyl, halo, haloC 1 -C 6 alkyl, amino, mono- or dialkylamino, mono- or dialkylaminocarbonyl, C 1 -C 6 alkyl-carbonylamino, C 0 -C 3 alkylenecarbocyclyl and C 0 -C 3 alkyleneheterocyclyl; R 5 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkyl or C 3 -C 7 cycloalkyl; R 6 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkylene-heterocyclyl, hydroxy, bromo, chloro or fluoro have utility in the treatment or prophylaxis of flaviviral infections such as HCV

  公式I的化合物： 以及其N-氧化物、盐和立体异构体 其中 A是OR 1 ，NHS(═O) p R 2 ；其中； R 1 是氢、C 1 -C 6 烷基、C 0 -C 3 烷基烯基环烷基、C 0 -C 3 烷基烯基杂环烷基； R 2 是C 1 -C 6 烷基、C 0 -C 3 烷基烯基环烷基、C 0 -C 3 烷基烯基杂环烷基； p独立地为1或2； n为3、4、5或6；— 表示一个可选的双键； L是N或CRz； Rz是H或与带星号的碳形成双键； Rq是H或当L为CRz时，Rq也可以是C 1 -C 6 烷基； Rr是喹唑啉基，可选择地取代一个、两个或三个取代基，每个取代基独立地选自C 1 -C 6 烷基、C 1 -C 6 烷氧基、羟基、卤素、卤代C 1 -C 6 烷基、氨基、单烷基或二烷基氨基、单烷基或二烷基氨基甲酰基、C 1 -C 6 烷基-甲酰氨基、C 0 -C 3 烷基烯基环烷基和C 0 -C 3 烷基烯基杂环烷基； R 5 是氢、C 1 -C 6 烷基、C 1 -C 6 烷氧基C 1 -C 6 烷基或C 3 -C 7 环烷基； R 6 是氢、C 1 -C 6 烷基、C 1 -C 6 烷氧基、C 0 -C 3 烷基烯基环烷基、C 0 -C 3 烷基烯基杂环烷基、羟基、溴、氯或氟在治疗或预防黄病毒感染如HCV中具有用途
• Macrocyclic Inhibitors of Hepatitis C Virus
  申请人：Wahling Horst

  公开号：US20090023758A1

  公开（公告）日：2009-01-22

  Compounds of the formula (I): and N-oxides, salts and stereoisomers thereof wherein A is OR 1 , NHS(═O) p R 2 , NHR 3 , NRaRb, C(═O)NHR 3 or C(═O)NRaRb wherein; R 1 is hydrogen, C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl; R 2 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl or NRaRb; R 3 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl, —OC 1 -C 6 alkyl, —OC 0 -C 3 alkylenecarbocyclyl, —OC 0 -C 3 alkyleneheterocyclyl; wherein any alkyl, carbocyclyl or heterocycylyl in R 1 , R 2 or R 3 are optionally substituted p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; Rq is H or when L is CRz, Rq can also be C 1 -C 6 alkyl; Ry and Ry′ are independently C 1 -C 6 alkyl; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; W is —CH 2 —, —O—, —OC(═O)NH—, —OC(═O)—, —S—, —NH—, —NRa, —NHS(═O) 2 —, —NHC(=0)NH— or —NHC(═O)—, —NHC(═S)NH— or a bond; R 8 is an optionally substituted ring system containing 1 or 2 saturated, partially saturated or unsaturated carbo or heterocyclic rings have utility in the inhibition of NS-3 serine proteases, such as flavivirus infections.

  式(I)的化合物：及其N-氧化物、盐和立体异构体，其中A为OR1、NHS(═O)pR2、NHR3、NRaRb、C(═O)NHR3或C(═O)NRaRb，其中；R1为氢、C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基；R2为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基或NRaRb；R3为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基、—OC1-C6烷基、—OC0-C3烷基环戊基、—OC0-C3烷基杂环戊基；其中R1、R2或R3中的任何烷基、环戊基或杂环戊基可选择性地被取代；p独立地为1或2；n为3、4、5或6；表示可选的双键；Rq为H或当L为CRz时，Rq也可以是C1-C6烷基；Ry和Ry′独立地为C1-C6烷基；L为N或CRz；Rz为H或与带星号的碳形成双键；W为—CH2—、—O—、—OC(═O)NH—、—OC(═O)—、—S—、—NH—、—NRa、—NHS(═O)2—、—NHC(=0)NH—或—NHC(═O)—、—NHC(═S)NH—或键；R8为含有1或2个饱和、部分饱和或不饱和碳或杂环环的可选择性取代的环系统，在NS-3丝氨酸蛋白酶的抑制中具有用途，例如黄病毒感染。
• 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。
• MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Simmen Kenneth Alan

  公开号：US20090281141A1

  公开（公告）日：2009-11-12

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers thereof, wherein X is N, CH and where X bears a double bond it is C; R 1 is —OR 1 , —NH—SO 2 R 6 ; 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; R 4 is isoquinolinyl optionally substituted with one, two or three substituents each independently selected from C 1-6 alkyl, C 1-6 alkoxy, hydroxy, halo, polyhaloC 1-6 alkyl, polyhaloC 1-6 alkoxy, amino, mono- or diC 1-6 alkylamino, mono- or diC 1-6 alkylaminocarbonyl, C 1-6 alkylcarbonyl-amino, aryl, and Het; n is 3, 4, 5, or 6; each dashed line (represented by - - - - - ) represents an optional double bond; R 5 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 6 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; each aryl is phenyl optionally substituted with one, two or three substituents; and each Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three 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.

  公式（I）及其N-氧化物，盐和立体异构体抑制HCV复制的抑制剂，其中X为N，CH，且X带有双键时为C; R1为—OR1，—NH—SO2R6; R2为氢，且当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; R4为异喹啉基，可选择地取代有一、两或三个取代基，每个取代基独立地选自C1-6烷基，C1-6烷氧基，羟基，卤素，多卤代C1-6烷基，多卤代C1-6烷氧基，氨基，一级或二级C1-6烷基氨基，一级或二级C1-6烷基氨基甲酰基，C1-6烷基甲酰氨基，芳基和Het; n为3、4、5或6;每个虚线（用- - - - -表示）表示可选的双键; R5为氢; 芳基; Het; C3-7环烷基，可选择地取代C1-6烷基; 或C1-6烷基，可选择地取代C3-7环烷基，芳基或与Het取代; R6为芳基; Het; C3-7环烷基，可选择地取代C1-6烷基; 或C1-6烷基，可选择地取代C3-7环烷基，芳基或与Het取代; 每个芳基为苯基，可选择地取代有一、两或三个取代基; 每个Het为含有1到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氮，氧和硫，并可选择地取代有一、两或三个取代基; 包含化合物（I）的制药组合物以及制备化合物（I）的过程。还提供了公式（I）的抑制剂与利托那韦的生物利用度组合。