(-)-(S)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine | 116476-11-0

• 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: (-)-(S)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine
• 英文别名: (S)-(-)-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-2H-1,4-benzothiazin-3(4H)-one；(2S)-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-1,4-benzothiazin-3-one
• CAS: 116476-11-0
• 化学式: C₁₆H₁₅NO₃S
• 分子量: 301.366
• InChiKey: OSIHAUUUEFEAKY-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-(S)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 、 3-溴-1-丙醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.42h， 生成 (-)-(S)-3,4-dihydro-2-<2-(3-bromopropoxy)-5-methoxyphenyl>-4-methyl-3-oxo-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
• 作为产物：
  描述：

  [4-methoxy-2-(4-methyl-3-oxo-1,4-benzothiazin-2-yl)phenyl] (2S,4S)-3-acetyl-2-(2-methoxyphenyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 生成 (-)-(S)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine
  参考文献：
  名称：

  J. Med. Chem. 1990, 33, 1898-1905

  摘要：

  DOI：
• 作为试剂：
  描述：

  (-)-(S)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 、 [4-methoxy-2-(4-methyl-3-oxo-1,4-benzothiazin-2-yl)phenyl] (2S,4S)-3-acetyl-2-(2-methoxyphenyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate 在 (-)-(S)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 作用下， 生成 3-溴-1-丙醇
  参考文献：
  名称：

  J. Med. Chem. 1990, 33, 1898-1905

  摘要：

  DOI：

文献信息

• Novel benzothiazine derivatives
  申请人：Santen Pharmaceutical Co., Ltd.

  公开号：US04786635A1

  公开（公告）日：1988-11-22

  This invention relates to novel benzothizine derivatives of the formula [I], processes for preparing them and therapeutic agents for circulatory diseases containing them as an active ingredient, ##STR1## wherein R.sup.1 is one or more groups selected from those consisting of hydrogen, lower alkyl, halogen, nitro, hydroxy, lower alkoxy, lower alkanoyloxy, amino, lower alkylamino and lower alkoxycarbonyloxy; R.sup.2 is hydrogen, lower alkyl or (C.sub.3 -C.sub.6)cycloalkyl; R.sup.3 is one or more groups selected from those consisting of hydrogen, lower alkyl, hydroxy, lower alkoxy, halogen, nitro, lower alkylenedioxy, lower alkanoyloxy, lower alkanoyl, amino, lower alkylamino, lower alkanoylamino and lower alkoxycarbonyloxy or ##STR2## R.sup.4 is hydrogen or lower alkyl.

  本发明涉及一种新的苯并噻嗪衍生物，其化学式为[I]，制备它们的方法以及包含它们作为活性成分的循环系统疾病治疗剂。 其中，R1是氢、低碳基、卤素、硝基、羟基、低烷氧基、低烷酰氧基、氨基、低烷基氨基和低烷氧羰基氧基等中的一个或多个基团；R2是氢、低碳基或（C3-C6）环烷基；R3是氢、低碳基、羟基、低烷氧基、卤素、硝基、低烷二氧基、低烷酰氧基、低烷酰基、氨基、低烷基氨基、低烷酰氨基和低烷氧羰基氧基中的一个或多个基团，或者是##STR2##；R4是氢或低碳基。
• 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.
• J. Med. Chem. 1990, 33, 1898-1905
  作者：

  DOI：——

  日期：——