1-(1,1-dimethylethyl) 2-methyl (2S,4R)-4-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-1,2-pyrrolidinedicarboxylate | 923604-80-2

• 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: 1-(1,1-dimethylethyl) 2-methyl (2S,4R)-4-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-1,2-pyrrolidinedicarboxylate
• 英文别名: 1-O-tert-butyl 2-O-methyl (2S,4R)-4-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxypyrrolidine-1,2-dicarboxylate
• CAS: 923604-80-2
• 化学式: C₂₈H₃₅N₃O₆S
• 分子量: 541.668
• InChiKey: BPZKTJJEVGIHIP-UTKZUKDTSA-N

物化性质

• 沸点：
  644.9±65.0 °C(Predicted)
• 密度：
  1.231±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  128
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(1,1-dimethylethyl) 2-methyl (2S,4R)-4-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-1,2-pyrrolidinedicarboxylate 在 Hoveyda-Grubbs catalyst second generation 、 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 47.0h， 生成 (2R,6R,14aR,16aS,Z)-N-(cyclopropylsulfonyl)-6-(2-(3,3-difluoropiperidin-1-yl)-2-oxoethyl)-2-(2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide
  参考文献：
  名称：

  Process for making a 4-amino-4-oxobutanoyl peptide cyclic analogue, an inhibitor of viral replication, and intermediates thereof

  摘要：

  本发明提供了一种制备化合物I的4-氨基-4-氧代丁酰肽及其环类似物的方法 及其药用盐。

  公开号：

  US09006423B2
• 作为产物：
  描述：

  (1S,4S)-3-氧代-2-噁-5-氮杂双环[2.2.1]庚烷-5-羧酸叔丁酯 在 4-二甲氨基吡啶 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 1-(1,1-dimethylethyl) 2-methyl (2S,4R)-4-{[8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinyl]oxy}-1,2-pyrrolidinedicarboxylate
  参考文献：
  名称：

  Process for making a 4-amino-4-oxobutanoyl peptide cyclic analogue, an inhibitor of viral replication, and intermediates thereof

  摘要：

  本发明提供了一种制备化合物I的4-氨基-4-氧代丁酰肽及其环类似物的方法 及其药用盐。

  公开号：

  US09006423B2

文献信息

• [EN] COMPOUNDS AS HEPATITIS C INHIBITORS AND USES THEREOF IN MEDICINE<br/>[FR] COMPOSÉS UTILISÉS EN TANT QU'INHIBITEURS DU VIRUS DE L'HÉPATITE C ET LEURS UTILISATIONS EN MÉDECINE
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2016127859A1

  公开（公告）日：2016-08-18

  Provided herein are compounds as hepatitis C inhibitors and uses thereof in medicine. Specifically, provided herein is a compound of Formula (I) or a stereoisomer, a tautomer, an enantiomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or hepatitis C diseases. Also provided herein are a pharmaceutically acceptable composition containing such compound and a method of treating HCV infection or hepatitis C diseases comprising administering the compound or pharmaceutical composition thereof disclosed herein.

  本文提供了一些作为丙型肝炎抑制剂的化合物及其在医学上的用途。具体来说，本文提供了一种式（I）的化合物或其立体异构体、互变异构体、对映体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药，可用于治疗HCV感染或丙型肝炎疾病。本文还提供了一种含有该化合物的药学上可接受的组合物，以及一种治疗HCV感染或丙型肝炎疾病的方法，包括给予本文所披露的化合物或药物组合物。
• [EN] A PROCESS FOR MAKING A 4-AMINO-4-OXOBUTANOYL PEPTIDE CYCLIC ANALOGUE, AN INHIBITOR OF VIRAL REPLICATION, AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE FABRICATION D'UN ANALOGUE CYCLIQUE DE PEPTIDE DE 4-AMINO-4-OXOBUTANOYLE, INHIBITEUR DE RÉPLICATION VIRALE ET LEURS INTERMÉDIAIRES
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2014145507A1

  公开（公告）日：2014-09-18

  The invention provides a process of preparing 4-amino-4-oxobutanoyl peptides and cyclic analogues thereof of Compound (I) and pharmaceutically acceptable salts thereof.

  该发明提供了一种制备化合物(I)的4-氨基-4-氧代丁酰肽及其环状类似物和药用可接受盐的方法。
• Macrocyclic inhibitors of hepatitis c virus
  申请人：Simmen Kenneth Alan

  公开号：US20090281140A1

  公开（公告）日：2009-11-12

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, 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 7 , —NH—SO 2 R 8 ; 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; R 4 is aryl or Het; n is 3, 4, 5, or 6; R 5 is halo, C 1-6 alkyl, hydroxy, C 1-6 alkoxy, phenyl, or Het; R 6 is C 1-6 alkoxy, or dimethylamino; R 7 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 8 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 optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms 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，盐和立体异构体的HCV复制抑制剂，其中每个虚线表示一个可选的双键; X是N，CH，其中X带有双键时是C; R1是-OR7，-NH-SO2R8; R2是氢，当X为C或CH时，R2也可以是C1-6烷基; R3是氢，C1-6烷基，C1-6烷氧基C1-6烷基，C3-7环烷基; R4是芳基或杂环基; n为3、4、5或6; R5是卤素，C1-6烷基，羟基，C1-6烷氧基，苯基或杂环基; R6是C1-6烷氧基或二甲基氨基; R7是氢; 芳基; 杂环基; C3-7环烷基，可选地用C1-6烷基取代; 或C1-6烷基，可选地用C3-7环烷基，芳基或杂环基取代; R8是芳基; 杂环基; C3-7环烷基，可选地用C1-6烷基取代; 或C1-6烷基，可选地用C3-7环烷基，芳基或杂环基取代; 芳基是苯基，可选地用一个、两个或三个取代基取代; 杂环基是一个含有1-4个氮、氧和硫杂原子的5或6元饱和、部分不饱和或完全不饱和的杂环环，可选地用一个、两个或三个取代基取代; 包含化合物（I）的药物组合物和制备化合物（I）的过程也提供。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。
• Macrocyclic Inhibitors Of Hepatitis C Virus
  申请人：Simmen Kenneth Alan

  公开号：US20110295012A1

  公开（公告）日：2011-12-01

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, 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 7 or —NH—SO 2 R 8 ; 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 aryl or Het; n is 3, 4, 5, or 6; R 5 is halo, C 1-6 alkyl, hydroxy, C 1-6 alkoxy, phenyl, or Het; R 6 is C 1-6 alkoxy or dimethylamino; R 7 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 8 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 optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms 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）的HCV复制抑制剂及其N-氧化物，盐和立体异构体，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—OR7或—NH—SO2R8；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；R4为芳基或杂环基；n为3、4、5或6；R5为卤素，C1-6烷基，羟基，C1-6烷氧基，苯基或杂环基；R6为C1-6烷氧基或二甲基氨基；R7为氢，芳基，杂环基，C3-7环烷基，可选地用C1-6烷基取代；或C1-6烷基，可选地用C3-7环烷基，芳基或杂环基取代；R8为芳基，杂环基，C3-7环烷基，可选地用C1-6烷基取代；或C1-6烷基，可选地用C3-7环烷基，芳基或杂环基取代；芳基为苯基，可选地用一个、两个或三个取代基取代；杂环基为含有1到4个氮、氧和硫杂原子的5或6成员饱和、部分不饱和或完全不饱和的杂环环，可选地用一个、两个或三个取代基取代；包含化合物（I）的药物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。
• MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Janssen Sciences Ireland UC

  公开号：US20160235737A1

  公开（公告）日：2016-08-18

  Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, 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 7 , —NH—SO 2 R 8 ; 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; R 4 is aryl or Het; n is 3, 4, 5, or 6; R 5 is halo, C 1-6 alkyl, hydroxy, C 1-6 alkoxy, phenyl, or Het; R 6 is C 1-6 alkoxy, or dimethylamino; R 7 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 8 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 optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms 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，其中每个虚线表示可选的双键；X为N、CH，当X带有双键时，它是C；R1为—OR7、—NH—SO2R8；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；R4为芳基或杂环基；n为3、4、5或6；R5为卤、C1-6烷基、羟基、C1-6烷氧基、苯基或杂环基；R6为C1-6烷氧基或二甲基氨基；R7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；R8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，可选地被一个、两个或三个取代基取代；杂环基是一个5或6成员饱和、部分不饱和或完全不饱和的杂环环，包含1到4个从氮、氧和硫中选择的杂原子，并可选地被一个、两个或三个取代基取代；含有化合物（I）的制药组合物和制备化合物（I）的过程也提供。还提供了公式（I）的抑制HCV的生物利用度与利托那韦的组合。