2-cyano-N-cyclohexyl-3-ethoxy-prop-2-enamide | 1048669-31-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯酯类
• 英文名称: 2-cyano-N-cyclohexyl-3-ethoxy-prop-2-enamide
• 英文别名: 2-cyano-N-cyclohexyl-3-ethoxyacrylamide；2-cyano-N-cyclohexyl-3-ethoxyprop-2-enamide
• CAS: 1048669-31-3
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: ANKFUQLJGCUNAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-cyano-N-cyclohexyl-3-ethoxy-prop-2-enamide 在 亚硝酸特丁酯 、 N,N-二异丙基乙胺 、 copper dichloride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 1.25h， 生成 methyl 4-[5-chloro-4-(cyclohexylcarbamoyl)pyrazol-1-yl]benzoate
  参考文献：
  名称：

  Novel Acidic 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitor with Reduced Acyl Glucuronide Liability: The Discovery of 4-[4-(2-Adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic Acid (AZD8329)

  摘要：

  Inhibition of 11 beta-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic syndrome. We report here the optimization of a carboxylic acid class of inhibitors from AZD4017 (1) to the development candidate AZD8329 (27). A structural change from pyridine to pyrazole together with structural optimization led to an improved technical profile in terms of both solubility and pharmacokinetics. The extent of acyl glucuronidation was reduced through structural optimization of both the carboxylic acid and amide substituents, coupled with a reduction in lipophilicity leading to an overall increase in metabolic stability.

  DOI：

  10.1021/jm301252n
• 作为产物：
  描述：

  2-氰基-N-环己基-乙酰胺 、 原甲酸三乙酯 在 乙酸酐 作用下， 反应 3.0h， 以75%的产率得到2-cyano-N-cyclohexyl-3-ethoxy-prop-2-enamide
  参考文献：
  名称：

  Synthesis, Characterisation and Antimicrobial Activity of Thiazole, Bisthiazole, Pyridone and Bispyridone Derivatives

  摘要：

  N-cyclohexyl-2-cyanoacetamide 与苯基异硫氰酸酯和硫反应生成噻唑烷和双噻唑烷衍生物。用异硫氰酸苯酯和 KOH 处理 N-环己基-2-氰基乙酰胺，然后与 α-卤化合物原位杂环化，得到噻唑衍生物。将 N-环己基-2-氰基乙酰胺与肉桂三酸酯处理，可得到吡啶酮和双吡啶酮衍生物。N-环己基-2-氰基乙酰胺与苯偶氮氯化物在吡啶中顺利结合。N-环己基-2-氰基乙酰胺与乙酰丙酮环缩合生成 1,1′-（乙烷-1,2-二基）双（4,6-二甲基-2-氧代-1,2-二氢吡啶-3-甲腈）。N- 环己基-2-氰乙酰胺、丙二腈和乙醛的三元缩合生成了双吡啶酮衍生物。对其中一些新化合物进行了抗菌和抗真菌测试。

  DOI：

  10.3184/030823410x12812857779516

文献信息

• Synthesis, Characterisation and Antimicrobial Activity of Thiazole, Bisthiazole, Pyridone and Bispyridone Derivatives
  作者：Gameel A. M. El-Hag Ali、Mohamed H. Helal、Yehia A. Mohamed、Ahmed A. Ali、Yousry A. Ammar

  DOI：10.3184/030823410x12812857779516

  日期：2010.8

  N-cyclohexyl-2-cyanoacetamide was reacted with phenyl isothiocyanates and sulfur to give thiazolidine and bisthiazolidine derivatives. Treatment of N-cyclohexyl-2-cyanoacetamide with phenyl isothiocyanate and KOH followed by in situ heterocyclisation with α-halo compounds gave thiazole derivatives. Treatment of N-cyclohexyl-2-cyanoacetamides with cinnamonitriles gave pyridone and bispyridone derivatives. N-cyclohexyl-2-cyanoacetamide coupled smoothly with benzene-diazonium chloride in pyridine. Cyclocondensation of N-cyclohexyl-2-cyanoacetamide with acetylacetone gave 1,1′-(ethane-1,2-diyl)bis(4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile). Ternary condensation of N-cyclohexyl-2-cyanoacetamide, malononitrile and acetaldehyde gave a bispyridone derivative. Some of the new compounds were tested against bacteria and some fungi.

  N-cyclohexyl-2-cyanoacetamide 与苯基异硫氰酸酯和硫反应生成噻唑烷和双噻唑烷衍生物。用异硫氰酸苯酯和 KOH 处理 N-环己基-2-氰基乙酰胺，然后与 α-卤化合物原位杂环化，得到噻唑衍生物。将 N-环己基-2-氰基乙酰胺与肉桂三酸酯处理，可得到吡啶酮和双吡啶酮衍生物。N-环己基-2-氰基乙酰胺与苯偶氮氯化物在吡啶中顺利结合。N-环己基-2-氰基乙酰胺与乙酰丙酮环缩合生成 1,1′-（乙烷-1,2-二基）双（4,6-二甲基-2-氧代-1,2-二氢吡啶-3-甲腈）。N- 环己基-2-氰乙酰胺、丙二腈和乙醛的三元缩合生成了双吡啶酮衍生物。对其中一些新化合物进行了抗菌和抗真菌测试。
• PYRAZOLE DERIVATIVES AS 11-BETA-HSD1 INHIBITORS
  申请人：Packer Martin John

  公开号：US20090221663A1

  公开（公告）日：2009-09-03

  A compound of Formula (I): and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

  公式（I）的化合物及其药学上可接受的盐，其中可变基团在其内部定义；还描述了它们在抑制11βHSD1方面的用途，制造它们的过程以及包含它们的制药组合物。
• Chemical compounds
  申请人：AstraZeneca AB

  公开号：US07816391B2

  公开（公告）日：2010-10-19

  A compound of formula (I): and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

  公式（I）的化合物及其药学上可接受的盐，其中变量基团的定义如下；还描述了它们在抑制11βHSD1方面的用途，制造它们的过程以及包含它们的制药组合物。
• Pyrazole Derivatives as 11-Beta-HSD1 Inhibitors
  申请人：Packer Martin John

  公开号：US20110224273A1

  公开（公告）日：2011-09-15

  A compound of formula (I): and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

  化合物I的式子及其药用可接受的盐，其中变量基团在定义范围内；还描述了它们在抑制11βHSD1方面的使用，制造它们的过程以及包含它们的制药组合物。
• Pyrazole derivatives as 11-beta-HSD1 inhibitors
  申请人：AstraZeneca AB

  公开号：US08344016B2

  公开（公告）日：2013-01-01

  A compound of formula (I): and pharmaceutically-acceptable salts thereof wherein the variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are also described.

  本发明涉及一种化合物及其药学上可接受的盐，其化学式为(I)。其中，变量基团在内部定义；还描述了它们在抑制11βHSD1方面的应用，制备它们的过程以及包含它们的药物组合物。