4,8-dichloro-2-(4-isopropylthiazole-2-yl)-7-methoxyquinoline | 923289-41-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4,8-dichloro-2-(4-isopropylthiazole-2-yl)-7-methoxyquinoline
• 英文别名: 4,8-Dichloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinoline；2-(4,8-dichloro-7-methoxyquinolin-2-yl)-4-propan-2-yl-1,3-thiazole
• CAS: 923289-41-2
• 化学式: C₁₆H₁₄Cl₂N₂OS
• 分子量: 353.272
• InChiKey: CCMNQDJAPMKGOV-UHFFFAOYSA-N

物化性质

• 沸点：
  494.1±55.0 °C(Predicted)
• 密度：
  1.344±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,8-dichloro-2-(4-isopropylthiazole-2-yl)-7-methoxyquinoline 在 sodium hydride 、 盐酸 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以75%的产率得到(2S,4R)-4-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester
  参考文献：
  名称：

  WO2007/14926

  摘要：

  公开号：
• 作为产物：
  描述：

  8-氯-7-甲氧基-2-(4-异丙基噻唑-2-基)-4-喹啉醇 在 三氯氧磷 作用下， 反应 0.5h， 以97%的产率得到4,8-dichloro-2-(4-isopropylthiazole-2-yl)-7-methoxyquinoline
  参考文献：
  名称：

  WO2007/14926

  摘要：

  公开号：

文献信息

• ANTIVIRAL COMPOUNDS
  申请人：Cai Zhenhong R.

  公开号：US20110135599A1

  公开（公告）日：2011-06-09

  The present application includes novel inhibitors of HCV, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

  本申请包括HCV的新型抑制剂，含有这些化合物的组合物，以及包括这些化合物的给药的治疗方法。
• 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：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。
• MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Simmen Kenneth Alan

  公开号：US20100240698A1

  公开（公告）日：2010-09-23

  Inhibitors of HCV of formula al and the N-oxides, salts, and stereochemically isomeric forms thereof, wherein R 1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 8 to 12 membered bicyclic heterocyclic ring system containing one nitrogen, and optionally one to three oxygen, sulfur or nitrogen, wherein said ring system 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, —OR 6 , —C(═O)OR 6 , —C(═O)R 7 , —C(═O)NR 5a R 5b , —C(═O)NHR 5c , —NR 5a R 5b , —NHR 5c , —NHSO p NR 5a R 5b , —NR 5a SO p R 8 , or —B(OR 6 ) 2 ; R 3 and R 4 are hydrogen or C 1-6 alkyl; or R 3 and R 4 taken together may form a C 3-7 cycloalkyl ring; 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 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, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be optionally substituted; 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aland及其N-氧化物、盐和立体化学同分异构体的HCV抑制剂，其中R1是芳基或饱和、部分不饱和或完全不饱和的5或6元单环或8到12元双环杂环环系统，其中含有一个氮，以及可选的1到3个氧、硫或氮，其中该环系统可以选择性地被取代；L是直接键，-O-，-O-C1-4烷二基，-O-CO-，-O-C（═O）-NR5a-或-O-C（═O）-NR5a-C1-4烷二基；R2是氢、-OR6、-C（═O）OR6、-C（═O）R7、-C（═O）NR5aR5b、-C（═O）NHR5c、-NR5aR5b、-NHR5c、-NHSOpNR5aR5b、-NR5aSOpR8或-B（OR6）2；R3和R4是氢或C1-6烷基；或R3和R4一起可以形成C3-7环烷基；n为3、4、5或6；p为1或2；芳基是苯基、萘基、茚基或1,2,3,4-四氢萘基，每个基团可以选择性地被取代；Het是一个5或6元饱和、部分不饱和或完全不饱和的杂环环，其中每个单独选择的1到4个杂原子分别来自氮、氧和硫，可选择性地与苯环融合，整个Het基团可以选择性地被取代；含有化合物（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HCV抑制剂与利托那韦的生物利用度组合。