7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide | 53413-83-5

• 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-3-isopropylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide
• 英文别名: BPDZ 73；(7-chloro-1,1-dioxo-1,2(4)-dihydro-1λ⁶-benzo[1,2,4]thiadiazin-3-yl)-isopropyl-amine；7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide；7-chloro-1,1-dioxo-N-propan-2-yl-4H-1λ6,2,4-benzothiadiazin-3-imine
• CAS: 53413-83-5
• 化学式: C₁₀H₁₂ClN₃O₂S
• 分子量: 273.743
• InChiKey: GFZIHBNQPGWJPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• 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 、 水 为溶剂， 生成 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide
  参考文献：
  名称：

  Hydroxylated Analogues of ATP-Sensitive Potassium Channel Openers Belonging to the Group of 6- and/or 7-Substituted 3-Isopropylamino-4H-1,2,4-benzothiadiazine 1,1-Dioxides: Toward an Improvement in Sulfonylurea Receptor 1 Selectivity and Metabolism Stability

  摘要：

  Diversely substituted 3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides are known to be potent K-ATP channel openers, with several drugs being selective for the SUR1/Kir6.2 channel subtype. This work examined the biological activity, tissue selectivity, and in vitro metabolic stability of hydroxylated analogues of 3-isopropylaminobenzothiadiazine dioxides. Because of the presence of a chiral center, the R and S isomers were prepared separately and characterized. R isomers were systematically found to be more potent and more selective than S isomers on pancreatic tissue (compared to vascular smooth muscle tissue), leading to compounds with an improved sulfonylurea receptor 1 (SUR1) selectivity. An in vitro metabolic study revealed that 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (1a) was rapidly biotransformed and led in part to a mixture of the corresponding (R)- and (S)-3-(1-hydroxy-2-propyl)amino-substituted derivatives. Radioisotopic experiments characterized one of the most potent and SUR1-selective enantiomers, (R)-7-chloro-3-(1-hydroxy-2-propyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide 13a, as being a K-ATP channel opener. Moreover, 13a exhibited an enhanced metabolic stability. Such a compound can be considered as a new lead candidate displaying improved physicochemical (hydrosolubility) and pharmacological (tissue selectivity) properties as well as improved metabolic stability compared to its nonhydroxylated counterpart, 1a.

  DOI：

  10.1021/jm200786z

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。
• Therapeutic agents targeting the NCCA-ATP channel and methods of use thereof
  申请人：University of Maryland, Baltimore

  公开号：EP2359832A2

  公开（公告）日：2011-08-24

  The present invention is directed to therapeutic compositions targeting the NCCa-ATP channel of an astrocyte, neuron or capillary endothelial cell and methods of using same. More specifically, agonists and antagonists of the NCCA-ATP channel are contemplated. The therapeutic compositions are used to treat cancer, more specifically, a metastatic brain tumor, wherein a tumor-brain barrier is present. Such treatments are contemplated in combination with conventional anti-cancer therapies. Alternatively, the compositions are used to prevent cell death and to treat cerebral edema that result from ischemia, due to interruption of blood flow, to tissue trauma or to increased tissue pressure.

  本发明涉及针对星形胶质细胞、神经元或毛细血管内皮细胞的 NCCa-ATP 通道的治疗组合物及其使用方法。更具体地说，考虑使用 NCCA-ATP 通道的激动剂和拮抗剂。治疗组合物用于治疗癌症，更具体地说，治疗存在肿瘤-脑屏障的转移性脑肿瘤。这种治疗可考虑与传统的抗癌疗法相结合。另外，组合物还可用于防止细胞死亡和治疗因血流中断、组织创伤或组织压力增加而导致的缺血性脑水肿。
• Therapeutic methods that target the NCCA-ATP channel
  申请人：Simard J. Marc

  公开号：US10583094B2

  公开（公告）日：2020-03-10

  The present invention is directed to therapeutic compositions targeting the NCCa-ATP channel of an astrocyte, neuron or capillary endothelial cell and methods of using same. More specifically, agonists and antagonists of the NCCa-ATP channel are contemplated. The therapeutic compositions are used to treat cancer, more specifically, a metastatic brain tumor, wherein a tumor-brain barrier is present. Such treatments are contemplated in combination with conventional anti-cancer therapies. Alternatively, the compositions are used to prevent cell death and to treat cerebral edema that result from ischemia, due to interruption of blood flow, to tissue trauma or to increased tissue pressure.

  本发明涉及针对星形胶质细胞、神经元或毛细血管内皮细胞的 NCCa-ATP 通道的治疗组合物及其使用方法。更具体地说，考虑使用 NCCa-ATP 通道的激动剂和拮抗剂。治疗组合物用于治疗癌症，更具体地说，治疗存在肿瘤-脑屏障的转移性脑肿瘤。这种治疗可考虑与传统的抗癌疗法相结合。另外，组合物还可用于防止细胞死亡和治疗因血流中断、组织创伤或组织压力增加而导致的缺血性脑水肿。
• 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：——
• THERAPEUTIC AGENTS TRAGETING THE NCCA-ATP CHANNEL AND METHODS OF USE THEREOF
  申请人：University of Maryland, Baltimore

  公开号：EP1802313A2

  公开（公告）日：2007-07-04