2-环己基噻唑-4-羧酸乙酯 | 923605-07-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-环己基噻唑-4-羧酸乙酯
• 英文名称: ethyl 2-cyclohexylthiazole-4-carboxylate
• 英文别名: 2-cyclohexylthiazole-4-carboxylic acid ethyl ester；ethyl 2-cyclohexylthiazol-4-carboxylate；ethyl 2-cyclohexyl-1,3-thiazole-4-carboxylate
• CAS: 923605-07-6
• 化学式: C₁₂H₁₇NO₂S
• 分子量: 239.338
• InChiKey: VACXECRSMZAFLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-环己基噻唑-4-羧酸乙酯 在 bis-triphenylphosphine-palladium(II) chloride 、 水 、 potassium acetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 4-(2-cyclohexyl-4-(morpholine-4-carbonyl)thiazol-5-yl)benzonitrile
  参考文献：
  名称：

  2,4,5-三取代噻唑类抗结核药的合成及生物学评价

  摘要：

  结核分枝杆菌的休眠和耐药形式在开发新的抗结核药物方面提出了挑战。在此，我们报道了三取代噻唑类作为抗结核剂的合成和评价。SAR研究已经确定了噻唑支架在C2处具有疏水取代基，在C4处具有酯官能度以及在C5处具有氢键受体特性的各种基团的需求。这导致鉴定出13h和13p为先导化合物。这些化合物选择性地抑制了休眠的结核分枝杆菌H37Ra菌株和结核分枝杆菌H37Rv。重要的是，13h和13p对CHO细胞无毒。这13p显示出对耐多药结核病分离株的活性。

  DOI：

  10.1016/j.ejmech.2019.05.082
• 作为产物：
  描述：

  环己甲酰胺 在 tetraphosphorus decasulfide 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 2.5h， 生成 2-环己基噻唑-4-羧酸乙酯
  参考文献：
  名称：

  2,4,5-三取代噻唑类抗结核药的合成及生物学评价

  摘要：

  结核分枝杆菌的休眠和耐药形式在开发新的抗结核药物方面提出了挑战。在此，我们报道了三取代噻唑类作为抗结核剂的合成和评价。SAR研究已经确定了噻唑支架在C2处具有疏水取代基，在C4处具有酯官能度以及在C5处具有氢键受体特性的各种基团的需求。这导致鉴定出13h和13p为先导化合物。这些化合物选择性地抑制了休眠的结核分枝杆菌H37Ra菌株和结核分枝杆菌H37Rv。重要的是，13h和13p对CHO细胞无毒。这13p显示出对耐多药结核病分离株的活性。

  DOI：

  10.1016/j.ejmech.2019.05.082

文献信息

• [EN] PIM KINASE INHIBITORS AND METHODS OF THEIR USE<br/>[FR] INHIBITEURS DE PIM KINASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：NOVARTIS AG

  公开号：WO2009109576A1

  公开（公告）日：2009-09-11

  The present invention relates to new compounds of Formulas (I) and (II), their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the inhibition of Pirn kinase activity and/or the prophylaxis or treatment of cancer.

  本发明涉及公式（I）和（II）的新化合物，它们的互变异构体、立体异构体和多型体，以及其药学上可接受的盐、酯、代谢物或前药，新化合物与药学上可接受的载体的组合物，以及新化合物的用途，单独或与至少一种额外治疗剂联合使用，用于抑制Pirn激酶活性和/或预防或治疗癌症。
• Pim kinase inhibitors and methods of their use
  申请人：Burger Matthew

  公开号：US20100216839A1

  公开（公告）日：2010-08-26

  The present invention relates to new compounds of Formulas I and II, their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the inhibition of Pim kinase activity and/or the prophylaxis or treatment of cancer.

  本发明涉及公式I和II的新化合物，它们的互变异构体、立体异构体和多晶形态，以及其药学上可接受的盐、酯、代谢物或前药，新化合物与药学上可接受的载体的组合物，以及新化合物的用途，单独或与至少一种额外治疗剂联合使用，在抑制Pim激酶活性和/或预防或治疗癌症方面。
• 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。