2-(2,6-dimethoxyphenoxy)-N-methyl-1-ethanamine | 96649-53-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2,6-dimethoxyphenoxy)-N-methyl-1-ethanamine
• 英文别名: [2-(2,6-Dimethoxyphenoxy)ethyl](methyl)amine；2-(2,6-dimethoxyphenoxy)-N-methylethanamine
• CAS: 96649-53-5
• 化学式: C₁₁H₁₇NO₃
• 分子量: 211.261
• InChiKey: DNJCIIFWUXYZRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2,6-dimethoxyphenoxy)-N-methyl-1-ethanamine 、 2-<2-(3-chloropropoxy)-5-methoxyphenyl>-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzothiazine 在 碳酸氢钠 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-[2-[3-[2-(2,6-Dimethoxyphenoxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one
  参考文献：
  名称：

  Synthesis and calcium ion antagonistic activity of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzothiazines

  摘要：

  As an extension of the previous investigation (J. Med. Chem. 1988, 31, 919), we synthesized a series of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H- 1,4-benzothiazines (3) and evaluated their Ca2+ antagonistic activities. Ca2+ antagonistic activity was measured with isolated depolarized guinea pig taenia cecum. On the basis of their potent Ca2+ antagonistic activity, six benzothiazines were selected and further evaluated for their vasocardioselectivity. Among these six compounds, the key compound 15 [3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[3,4- (methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo- 2H-1,4-benzothiazine hydrogen fumarate] was recognized as having the lowest cardioselectivity. Following optical resolution, the absolute configuration of the compound's optically active enantiomer was determined by means of X-ray crystallography of a synthetic precursor (+)-4a. The Ca2+ antagonistic activity of 15 was found to reside primarily in (+)-15 (which was about 7 times more potent than (-)-15). The in vitro study showed that (+)-15 had a low cardioselectivity compared to verapamil and diltiazem. This result suggests that (+)-15 would exhibit less adverse effects due to cardiac inhibition than diltiazem and verapamil in therapeutic use.

  DOI：

  10.1021/jm00169a011
• 作为产物：
  描述：

  2-(2-氯乙氧基)-1,3-二甲氧基苯 、 甲胺 以 乙醇 为溶剂， 反应 70.0h， 以60%的产率得到2-(2,6-dimethoxyphenoxy)-N-methyl-1-ethanamine
  参考文献：
  名称：

  Structure-activity relationships for prazosin and WB 4101 analogs as .alpha.1-adrenoreceptor antagonists

  摘要：

  Several alpha-adrenoreceptor antagonists were prepared by coupling one of the two moieties of WB 4101 (1) with one of the two moieties of prazosin (2). Their blocking activity and relative selectivity on alpha 1- and alpha 2-adrenoreceptors were evaluated in the isolated rat vas deferens. Although retaining a significant selectivity toward alpha 1-adrenoreceptors, all the drugs were weaker antagonists than the parent compounds 1 and 2. Opening the piperazine ring of 2 gave 3, which displayed a very high activity and selectivity toward alpha 1-adrenoreceptors (alpha 1/alpha 2 = 3890). This may have relevance in understanding the mode of action of prazosin. In addition, 3 may represent a valuable tool in the characterization of alpha-adrenoreceptor subtypes.

  DOI：

  10.1021/jm00147a042

文献信息

• FUJITA, MASANOBU;ITO, SUSUMU;OTA, ATSUTOSHI;KATO, NOBUHARU;YAMAMOTO, KOJI+, J. MED. CHEM., 33,(1990) N, C. 1898-1905
  作者：FUJITA, MASANOBU、ITO, SUSUMU、OTA, ATSUTOSHI、KATO, NOBUHARU、YAMAMOTO, KOJI+

  DOI：——

  日期：——
• GIARDINA, D.;BERTINI, R.;BRANCIA, E.;BRASILI, L.;MELCHIORRE, C., J. MED. CHEM., 1985, 28, N 9, 1354-1357
  作者：GIARDINA, D.、BERTINI, R.、BRANCIA, E.、BRASILI, L.、MELCHIORRE, C.

  DOI：——

  日期：——
• Synthesis and calcium ion antagonistic activity of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzothiazines
  作者：Masanobu Fujita、Susumu Ito、Atsutoshi Ota、Nobuharu Kato、Koji Yamamoto、Yoichi Kawashima、Hideyasu Yamauchi、Junichi Iwao

  DOI：10.1021/jm00169a011

  日期：1990.7

  As an extension of the previous investigation (J. Med. Chem. 1988, 31, 919), we synthesized a series of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H- 1,4-benzothiazines (3) and evaluated their Ca2+ antagonistic activities. Ca2+ antagonistic activity was measured with isolated depolarized guinea pig taenia cecum. On the basis of their potent Ca2+ antagonistic activity, six benzothiazines were selected and further evaluated for their vasocardioselectivity. Among these six compounds, the key compound 15 [3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[3,4- (methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo- 2H-1,4-benzothiazine hydrogen fumarate] was recognized as having the lowest cardioselectivity. Following optical resolution, the absolute configuration of the compound's optically active enantiomer was determined by means of X-ray crystallography of a synthetic precursor (+)-4a. The Ca2+ antagonistic activity of 15 was found to reside primarily in (+)-15 (which was about 7 times more potent than (-)-15). The in vitro study showed that (+)-15 had a low cardioselectivity compared to verapamil and diltiazem. This result suggests that (+)-15 would exhibit less adverse effects due to cardiac inhibition than diltiazem and verapamil in therapeutic use.
• Structure-activity relationships for prazosin and WB 4101 analogs as .alpha.1-adrenoreceptor antagonists
  作者：Dario Giardina、Rosaria Bertini、Egle Brancia、Livio Brasili、Carlo Melchiorre

  DOI：10.1021/jm00147a042

  日期：1985.9

  Several alpha-adrenoreceptor antagonists were prepared by coupling one of the two moieties of WB 4101 (1) with one of the two moieties of prazosin (2). Their blocking activity and relative selectivity on alpha 1- and alpha 2-adrenoreceptors were evaluated in the isolated rat vas deferens. Although retaining a significant selectivity toward alpha 1-adrenoreceptors, all the drugs were weaker antagonists than the parent compounds 1 and 2. Opening the piperazine ring of 2 gave 3, which displayed a very high activity and selectivity toward alpha 1-adrenoreceptors (alpha 1/alpha 2 = 3890). This may have relevance in understanding the mode of action of prazosin. In addition, 3 may represent a valuable tool in the characterization of alpha-adrenoreceptor subtypes.