3,4-Dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine | 93848-37-4

• 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-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine
• 英文别名: (-)-3,4-dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine；2-(2-hydroxy-5-methoxyphenyl)-4-methyl-1,4-benzothiazin-3-one
• CAS: 93848-37-4
• 化学式: C₁₆H₁₅NO₃S
• 分子量: 301.366
• InChiKey: OSIHAUUUEFEAKY-UHFFFAOYSA-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：

  3,4-Dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 在 sodium hydride 、 碳酸氢钠 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 2H-1,4-Benzothiazin-3(4H)-one, 2-[2-[3-[[2-(1,3-benzodioxol-5-yloxy)ethyl]methylamino]propoxy]-5-methoxyphenyl]-4-methyl-, (2R)-, (2E)-2-butenedioate (1:1) (9CI)
  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 3,4-Dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine
  参考文献：
  名称：

  IWAO, JUN-ICHI;ISO, TADASHI;OYA, MASAYUKI

  摘要：

  DOI：
• 作为试剂：
  描述：

  (2S,4S)-3-acetyl-5,5-dimethyl-2-(2-methoxyphenyl)-4-thiazolidinecarboxylic acid 、 3,4-Dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 在 3,4-Dihydro-2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3-oxo-2H-1,4-benzothiazine 作用下， 以18.1的产率得到[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
  参考文献：
  名称：

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

  摘要：

  DOI：

文献信息

• A Novel, Convenient Synthesis of 2-Aryl-3-oxo-3,4-dihydro-2<i>H</i>-1,4-benzothiazines
  作者：Masanobu Fujita、Atsutoshi Ota、Susumu Ito、Koji Yamamoto、Yoichi Kawashima

  DOI：10.1055/s-1988-27648

  日期：——

  A novel method for the synthesis of 2-aryl-3-oxo-3,4-dihydro-2H-1, 4-benzothiazines consists of a Friedel-Crafts type reaction of substituted benzenes with 2-chloro-3-oxo-3,4-dihydro-2H-1,4-benzothiazines. This method is convenient by virtue of its simplicity and the good yields.

  一种合成2-芳基-3-氧代-3,4-二氢-2H-1,4-苯并噻嗪的新方法是将取代苯与2-氯-3-氧代-3,4-二氢-2H-1,4-苯并噻嗪进行Friedel-Crafts类型的反应。该方法因其简单性和良好的产率而便捷。
• Platelet anti-aggregative- and calcium antagonistic
  申请人：Santen Pharmaceutical Co., Ltd.

  公开号：US04584300A1

  公开（公告）日：1986-04-22

  This invention relates to benzothiazine derivatives represented by the formula [I] and salts thereof, which are useful for treatment of cardiovascular diseases. ##STR1##

  本发明涉及由公式[I]表示的苯并噻唑衍生物及其盐，其对治疗心血管疾病有用。 ##STR1##
• 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.

  本发明涉及公式[I]的新型苯并噻嗪衍生物，其制备过程以及作为循环系统疾病治疗剂的活性成分的药物，其中R.sup.1是氢、低级烷基、卤素、硝基、羟基、低级烷氧基、低级烷酰氧基、氨基、低级烷基氨基和低级烷氧羰基氧基中的一种或多种基团；R.sup.2是氢、低级烷基或（C.sub.3-C.sub.6）环烷基；R.sup.3是氢、低级烷基、羟基、低级烷氧基、卤素、硝基、低级烷二氧基、低级烷酰氧基、低级烷酰基、氨基、低级烷基氨基、低级烷酰胺基和低级烷氧羰基氧基中的一种或多种基团，或者##STR2## R.sup.4是氢或低级烷基。
• NOVEL BENZOTHIAZINE DERIVATIVES
  申请人：SANTEN PHARMACEUTICAL CO., LTD.

  公开号：EP0237573A1

  公开（公告）日：1987-09-23

  Novel benzothiazine derivatives represented by the following general formula (I), process for their preparation, and agents for treating diseases of circulatory organs containing these compounds as effective ingredients: wherein R' represents one or more groups selected from among a hydrogen atom, a lower alkyl group, a halogen atom, a nitro group, a hydroxy group, a lower alkoxy group, a lower alkanoyloxy group, an amino group, a lower alkylamino group and a lower alkoxycarbonyloxy group, R2 represents a hydrogen atom, a lower alkyl group or a (C3 - C6) cycloalkyl group, R3 represents one or more of a hydrogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group, a halogen atom, a nitro group, a lower alkylenedioxy group, a lower alkanoyloxy group, a lower alkanoyl group, an amino group, a lower alkylamino group, a lower alkanoylamino group and a lower alkoxycarbonyloxy group, or (CH2)n, R4 represents a hydrogen atom or a lower alkyl group, A and B which may be the same or different and each represents a lower alkylene group containing 1 to 6 carbon atoms, and n represents 3 or4.

  由以下通式(I)表示的新型苯并噻嗪衍生物、其制备方法以及含有这些化合物作为有效成分的治疗循环器官疾病的制剂：其中 R'代表一个或多个选自氢原子、低级烷基、卤素原子、硝基、羟基、低级烷氧基、低级烷酰氧基、氨基、低级烷基氨基和低级烷氧基羰基的基团；R2 代表氢原子、低级烷基或 (C3 - C6) 环烷基；R3 代表氢原子、低级烷基、羟基R4 代表氢原子或低级烷基，A 和 B 可以相同或不同，各自代表含有 1 至 6 个碳原子的低级亚烷基，n 代表 3 或 4。
• FUJITA, MASANOBU;OTA, ATSUTOSHI;ITO, SUSUMU;YAMAMOTO, KOJI;KAWASHIMA, YOI+, SYNTHESIS,(1988) N, C. 599-604
  作者：FUJITA, MASANOBU、OTA, ATSUTOSHI、ITO, SUSUMU、YAMAMOTO, KOJI、KAWASHIMA, YOI+

  DOI：——

  日期：——