(7-chloro-1,1-dioxo-1,2(4)-dihydro-1λ⁶-benzo[1,2,4]thiadiazin-3-yl)-cyclopropyl-amine | 53413-84-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: (7-chloro-1,1-dioxo-1,2(4)-dihydro-1λ⁶-benzo[1,2,4]thiadiazin-3-yl)-cyclopropyl-amine
• 英文别名: 7-chloro-N-cyclopropyl-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-3-imine；7-chloro-N-cyclopropyl-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-imine
• CAS: 53413-84-6
• 化学式: C₁₀H₁₀ClN₃O₂S
• 分子量: 271.727
• InChiKey: KKYMGLVGVRQGDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-chloro-2,3-dihydro-3-oxo-4H-1,2,4-benzothiadiazine 在 吡啶 、 tetraphosphorus decasulfide 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成 (7-chloro-1,1-dioxo-1,2(4)-dihydro-1λ⁶-benzo[1,2,4]thiadiazin-3-yl)-cyclopropyl-amine
  参考文献：
  名称：

  Toward Tissue-Selective Pancreatic B-Cells K_ATP Channel Openers Belonging to 3-Alkylamino-7-halo-4H-1,2,4-benzothiadiazine 1,1-Dioxides

  摘要：

  3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K-ATP channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position. Thus, 3-(ethylamino)-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide (11) expressed a marked inhibitory activity on pancreatic B-cells (IC50 = 1 muM) associated with a weak vasorelaxant effect (ED50 > 300 muM), whereas 7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide (27), which was only slightly active on insulin-secreting cells (IC50 > 10 muM), was found to be very potent on vascular smooth muscle cells (ED50 = 0.29 muM). Radioisotopic and electrophysiological. investigations performed with 7-chlorinated, 7-iodinated, and 7-fluorinated 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides confirmed that the drugs activated K-ATP channels. The present data revealed that subtle structural modifications of 3-(alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides can generate original compounds activating K-ATP channels and exhibiting different in vitro tissue selectivity profiles.

  DOI：

  10.1021/jm021117w

文献信息

• Therapeutics for the treatment of glaucoma
  申请人：MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH

  公开号：US10981951B2

  公开（公告）日：2021-04-20

  The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure.

  本发明提供苯并噻二嗪和色苷衍生物，特别是用于治疗青光眼、视网膜病变、治疗年龄相关性黄斑变性、治疗、稳定和/或抑制血液和淋巴血管生成，并通过向眼睛内给予药学有效量的前药，其中前药特异性调节KATP通道以降低眼内压力。
• Raffa; Di Bella; Ferrari, Farmaco, Edizione Scientifica, 1974, vol. 29, # 6, p. 411 - 423
  作者：Raffa、Di Bella、Ferrari、Rinaldi、Ferrari

  DOI：——

  日期：——
• 1,2,4-BENZOTHIADIAZINE DERIVATIVES, THEIR PREPARATION AND USE
  申请人：Université de Liège

  公开号：EP0906297B1

  公开（公告）日：2004-02-25
• NOVEL THERAPEUTICS FOR THE TREATMENT OF GLAUCOMA
  申请人：Mayo Foundation for Medical Education and Research

  公开号：EP3099304A1

  公开（公告）日：2016-12-07
• USE OF DIAZOXIDE FOR SUPPRESSING THE PLASMA INSULIN LEVEL IN A MAMMAL
  申请人：De Boer Johannes Mathijs Maria

  公开号：US20100234362A1

  公开（公告）日：2010-09-16

  The present invention relates to the use of a potassium channel activator in the manufacture of a medicament for suppressing the fasting plasma insulin level and/or postabsorptive insulin level in a mammal in need thereof, wherein the fasting and/or postabsorptive plasma insulin level is reduced to about 5 mU/l or less. The present invention also relates to the use of a potassium channel activator in the manufacture of a medicament for suppressing the fasting plasma insulin level and/or postabsorptive insulin level in a mammal in need thereof for treating or preventing obesity, obesity related disorders and conditions and other disorders and conditions related to weight gain in a mammal in need thereof, said method comprising orally administering to said mammal in need thereof a daily dosage of about 5 mg to about 1200 mg, calculated on a Diazoxide active weight basis.