3,4-dihydro-2-<5-methoxy-2<3-ethyl>amino>propoxy>phenyl>-4-methyl-3-oxo-2H-1,4-benzothiazine hydrogen fumarate | 123388-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3,4-dihydro-2-<5-methoxy-2<3-ethyl>amino>propoxy>phenyl>-4-methyl-3-oxo-2H-1,4-benzothiazine hydrogen fumarate
• 英文别名: 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 fumarate；Semotiadil recemate fumarate；2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazin-3-one;(E)-but-2-enedioic acid
• CAS: 123388-25-0
• 化学式: C₄H₄O₄*C₂₉H₃₂N₂O₆S
• 分子量: 652.722
• InChiKey: DIEJEELGDWGUCV-WLHGVMLRSA-N

物化性质

• 熔点：
  131-133 °C(Solv: ethanol (64-17-5))
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  12

制备方法与用途

生物活性

Semotiadil recemate fumarate 是 Semotiadil fumarate 的外消旋体。Semotiadil fumarate 是一种新型的血管选择性的 Ca2+ 通道拮抗剂。

靶点

Ca ²⁺ channel

体外研究

Semotiadil in a concentration of 1 μM produces an inhibition of 12.4±9.7% and in a concentration of 10 μM an inhibition of 25±11.0%. Effects of Semotiadil on the voltage-dependent Ca current (ICa) are investigated in dispersed smooth muscle cells of the rabbit portal vein. At a holding potential of -100 mV, Semotiadil (> or =0.1 μM; dissolved in DMSO) inhibits the ICa in a concentration-dependent manner (IC ₅₀ =2.0 μM). At a holding potential of -80 mV or -60 mV, the concentration-inhibition curve observed in the presence of Semotiadil is shifted to the left compared with that observed at -100 mV; and Semotiadil shifts the voltage-dependent inactivation curve to the left. The curve for the decay of ICa is fitted with two time constants. Semotiadil (<1 μM) reduces the slow but not the fast time constant. The curve for the recovery from ICa inactivation also consisted of two time constants, and Semotiadil (1 microM) prolongs the slow recovery. Semotiadil dissolved in deionized water more potently inhibits ICa than Semotiadil dissolved in DMSO.

体内研究

Semotiadil fumarate, a novel benzothiazine calcium antagonist, is given alone or in combination with either Enalapril or trichlormethiazide to conscious, spontaneously hypertensive, rats daily for 2 weeks. When given alone, the antihypertensive effects of Semotiadil (10 mg/kg, p.o.) and Enalapril (5 mg/kg, p.o.) first became apparent after the 3rd dose and thereafter the effects appeared to develop daily although this effect had waned by the time of the next dose. These results indicate that combined daily dosing of Semotiadil, especially with Enalapril, each at relatively low doses may be able to control hypertension in a continuous manner.

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-2-<5-methoxy-2<3-ethyl>amino>propoxy>phenyl>-4-methyl-3-oxo-2H-1,4-benzothiazine hydrogen fumarate 、 甲苯 生成 2-[2-[3-[2-(1,3-benzodioxol-5-yloxy)ethyl-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-1,4-benzothiazine-3-thione;(E)-but-2-enedioic acid
  参考文献：
  名称：

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

  摘要：

  DOI：
• 作为产物：
  描述：

  2-[2-(3-bromopropoxy)-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzothiazine 生成 3,4-dihydro-2-<5-methoxy-2<3-ethyl>amino>propoxy>phenyl>-4-methyl-3-oxo-2H-1,4-benzothiazine hydrogen fumarate
  参考文献：
  名称：

  Novel benzothiazine derivatives

  摘要：

  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。

  公开号：

  US04786635A1

文献信息

• 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。
• DRUG FOR IMPROVING BRAIN FUNCTION
  申请人：SANTEN PHARMACEUTICAL CO., LTD

  公开号：EP0429676A1

  公开（公告）日：1991-06-05

  A drug for improving brain functions, comprising a specified 2-phenyl-3-oxo-2H-1,4-benzothiazine derivative. It is effective in treating various diseases accompanied by lowering in brain functions, such as those caused by cerebral ischemia, e.g. cerebral infarction or transient cerebral ischemia, those caused as the sequela of brain edema, cerebral hemorrhage, etc., those caused by injuries, e.g. contusion, or central nervous system degeneration and regressive diseases, e.g. dementia, psychosis. neurosis, or Alzheimer disease.

  一种改善脑功能的药物，由特定的 2-苯基-3-氧代-2H-1,4-苯并噻嗪衍生物组成。它能有效治疗伴有脑功能降低的各种疾病，如脑缺血引起的疾病，如脑梗塞或短暂性脑缺血，脑水肿、脑出血等后遗症引起的疾病，外伤引起的疾病，如挫伤，或中枢神经系统退化和退行性疾病，如痴呆、精神病、神经衰弱或阿尔茨海默病。
• IWAO, JUN-ICHI;ISO, TADASHI;OYA, MASAYUKI
  作者：IWAO, JUN-ICHI、ISO, TADASHI、OYA, MASAYUKI

  DOI：——

  日期：——
• US4786635A
  申请人：——

  公开号：US4786635A

  公开（公告）日：1988-11-22
• US6281208B1
  申请人：——

  公开号：US6281208B1

  公开（公告）日：2001-08-28