3-ethyl-2-methyl-5,6,7,8-tetrahydroquinolin-4-ol | 737778-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-ethyl-2-methyl-5,6,7,8-tetrahydroquinolin-4-ol
• 英文别名: 3-ethyl-2-methyl-5,6,7,8-tetrahydro-1H-quinolin-4-one
• CAS: 737778-20-0
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: ZVVUGUPZWWJYBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-ethyl-2-methyl-5,6,7,8-tetrahydroquinolin-4-ol 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 反应 1.0h， 以87%的产率得到4-chloro-3-ethyl-2-methyl-5,6,7,8-tetrahydroquinoline
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x
• 作为产物：
  描述：

  2-乙基乙酰乙酸乙酯 在 silica gel 、 镍 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 二苯醚 、 甲苯 为溶剂， 70.0~250.0 ℃ 、2.0 MPa 条件下， 反应 1.0h， 生成 3-ethyl-2-methyl-5,6,7,8-tetrahydroquinolin-4-ol
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x

文献信息

• [EN] ANTAGONISTS FOR ALPHA-2 ADRENOCEPTORS<br/>[FR] ANTAGONISTES POUR RECEPTEURS ALPHA-2 ADRENERGIQUES
  申请人：JUVANTIA PHARMA LTD OY

  公开号：WO2004067513A1

  公开（公告）日：2004-08-12

  The invention provides a compound of formula (I), wherein Q, Y, A, Ra, Rb, R1 to R4, u and t are as defined in claim 1, or a pharmaceutically acceptable salt or ester thereof, useful as an alpha-2 antagonist. The compounds of formula (I) can be used for the treatment of diseases or conditions where antagonists of alpha-2 adrenoceptors are indicated to be effective.

  该发明提供了一种具有式（I）的化合物，其中Q、Y、A、Ra、Rb、R1至R4、u和t如权利要求1中定义，或其药用可接受的盐或酯，可用作α-2拮抗剂。式（I）的化合物可用于治疗需要α-2肾上腺素受体拮抗剂有效的疾病或症状。
• Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists
  作者：Iisa P. J. Höglund、Satu Silver、Mia T. Engström、Harri Salo、Andrei Tauber、Hanna-Kaisa Kyyrönen、Pauli Saarenketo、Anna-Marja Hoffrén、Kurt Kokko、Katariina Pohjanoksa、Jukka Sallinen、Juha-Matti Savola、Siegfried Wurster、Oili A. Kallatsa

  DOI：10.1021/jm060262x

  日期：2006.10.1

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.