3,4-dihydro-2-<5-methoxy-2-<3-ethyl>amino>propoxy>phenyl>-4-methyl-2H-1,4-benzothiazine | 127732-68-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 3,4-dihydro-2-<5-methoxy-2-<3-ethyl>amino>propoxy>phenyl>-4-methyl-2H-1,4-benzothiazine
• 英文别名: N-[2-(1,3-benzodioxol-5-yloxy)ethyl]-3-[4-methoxy-2-(4-methyl-2,3-dihydro-1,4-benzothiazin-2-yl)phenoxy]-N-methylpropan-1-amine
• CAS: 127732-68-7
• 化学式: C₂₉H₃₄N₂O₅S
• 分子量: 522.665
• InChiKey: YRKXDSQFNDBXPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4-Dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 在 calcium borohydride 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 3,4-dihydro-2-<5-methoxy-2-<3-ethyl>amino>propoxy>phenyl>-4-methyl-2H-1,4-benzothiazine
  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

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：——
• 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.