6-异丙基吡啶-2-羧酸(6-乙酰基-3-甲氧基-2-甲基苯基)酰胺 | 923604-99-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 6-异丙基吡啶-2-羧酸(6-乙酰基-3-甲氧基-2-甲基苯基)酰胺
• 英文名称: 6-isopropylpyridine-2-carboxylic acid (6-acetyl-3-methoxy-2-methylphenyl)amide
• 英文别名: 6-Isopropylpyridine-2-carboxylic acid (6-acetyl-3-methoxy-2-methyl-phenyl)amide；N-(6-acetyl-3-methoxy-2-methylphenyl)-6-propan-2-ylpyridine-2-carboxamide
• CAS: 923604-99-3
• 化学式: C₁₉H₂₂N₂O₃
• 分子量: 326.395
• InChiKey: IBOWZDAVODTSBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-异丙基吡啶-2-羧酸(6-乙酰基-3-甲氧基-2-甲基苯基)酰胺 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 生成 4-hydroxy-2-(6-isopropyl-2-pyridyl)-7-methoxy-8-methyl-quinoline
  参考文献：
  名称：

  Structure–activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350

  摘要：

  SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl) sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (K-i = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.088
• 作为产物：
  描述：

  6-异丙基甲酸吡啶 、 2-甲基-3-氨基-4-乙酰基苯甲醚 在 吡啶 、 三氯氧磷 作用下， 反应 2.5h， 以72%的产率得到6-异丙基吡啶-2-羧酸(6-乙酰基-3-甲氧基-2-甲基苯基)酰胺
  参考文献：
  名称：

  WO2007/14926

  摘要：

  公开号：

文献信息

• 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：Tibotec Pharmaceuticals Ltd.

  公开号：US08153800B2

  公开（公告）日：2012-04-10

  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; R1 is —OR7 or —NH—SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, or C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, 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.

  HCV复制抑制剂的化学式(I)，其N-氧化物、盐和立体异构体，其中每个虚线代表一个可选的双键；X为N，CH，其中X带有双键时为C；R1为—OR7或—NH—SO2R8；R2为氢，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至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；含有化合物(I)的药物组合物和制备化合物(I)的方法。还提供了与利托那韦的HCV抑制剂的生物利用度组合。
• 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。
• Macrocylic inhibitors of hepatitis C virus
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：US08349869B2

  公开（公告）日：2013-01-08

  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; R1 is —OR7, —NH—SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, 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，其中每个虚线表示可选的双键; X为N，CH，其中X带有双键时为C; R1为—OR7，—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，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、二或三个取代基取代; 杂环基是一个5或6成员的饱和，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; 包含化合物（I）的制药组合物和制备化合物（I）的过程。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。