6-chloro-3-isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide | 194086-39-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 6-chloro-3-isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
• 英文别名: NNC 55-0118；6-Chloro-3-isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide；6-chloro-3-isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine-1,1-dioxide；Nnc-55-0118；6-chloro-1,1-dioxo-N-propan-2-yl-4H-thieno[3,2-e][1,2,4]thiadiazin-3-imine
• CAS: 194086-39-0
• 化学式: C₈H₁₀ClN₃O₂S₂
• 分子量: 279.771
• InChiKey: NDBOSDQLHXHDSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  氢氧化钾 、 6-chloro-3-isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 在 钯 乙醇 、 水 、 water ethanol 、 乙酸乙酯 、 甲烷 、 title compound 、 silica gel 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、13.51 MPa 条件下， 反应 72.0h， 生成 3-Isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
  参考文献：
  名称：

  Fused 1,2,4-thiadiazine derivatives, their preparation and use

  摘要：

  本发明涉及由式(I)表示的1,2,4-噻二嗪和1,4-噻嗪衍生物，其中A、B、D、R1、R2、R3和R4在说明书中有定义，描述了它们的组成以及制备这些化合物的方法。这些化合物在治疗中枢神经系统、心血管系统、肺系统、胃肠系统和内分泌系统疾病方面具有用途。

  公开号：

  US06225310B1
• 作为产物：
  描述：

  N-(3-amino-5-chloro-2-thienylsulfonyl)-N'-isopropylthiourea 在 光气 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 6-chloro-3-isopropylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
  参考文献：
  名称：

  6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-Dioxide Derivatives Potently and Selectively Activate ATP Sensitive Potassium Channels of Pancreatic β-Cells

  摘要：

  6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives were synthesized and characterized as activators of adenosine 5'-triphosphate (ATP) sensitive potassium (K-ATP) channels in the beta-cells by measuring effects on membrane potential and insulin release in vitro. The effects on vascular tissue in vitro were measured on rat aorta and small mesenteric vessels. Selected compounds were characterized as competitive inhibitors of [H-3]glibenclamide binding to membranes of HEK293 cells expressing human SUR1/Kir6.2 and as potent inhibitors of insulin release in isolated rat islets. 6-Chloro-3-(1-methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (54) was found to bind and activate the SUR1/Kir6.2 KATP channels in the low nanomolar range and to be at least 1000 times more potent than the reference compound diazoxide with respect to inhibition of insulin release from rat islets. Several compounds, e.g., 3-propylamino- (30), 3-isopropylamino- (34), 3-(S)-sec-butylamino- (37), and 3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (53), which were found to be potent and beta-cell selective activators of K-ATP channels in vitro, were found to inhibit insulin secretion in rats with minimal effects on blood pressure and to exhibit good oral pharmacokinetic properties.

  DOI：

  10.1021/jm0208121

文献信息

• Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their
  申请人：Novo Nordisk A/S

  公开号：US05889002A1

  公开（公告）日：1999-03-30

  1,2,4-Thiadiazine and 1,4-thiazine derivatives represented by the formula ##STR1## wherein A, B, D, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are defined in the description, compositions thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinologic system.

  1,2,4-噻二嗪和1,4-噻嗪衍生物，其代表性结构式如上，其中A、B、D、R1、R2、R3和R4在描述中有定义，以及它们的组合物和制备方法被描述。这些化合物在治疗中枢神经系统疾病、心血管系统疾病、肺系统疾病、胃肠系统疾病和内分泌系统疾病方面具有用途。
• Novel process
  申请人：——

  公开号：US20020119969A1

  公开（公告）日：2002-08-29

  The present invention relates to a novel processes for preparing pharmaceutically active fused 1,2,4-thiadiazine derivatives of general formula (I) as defined in the description and intermediates therefore.

  本发明涉及一种用于制备具有药用活性的通式(I)所定义的新型融合1,2,4-噻二嗪衍生物的方法，以及相关的中间体。
• Use of potassium channel agonists for the treatment of cancer
  申请人：——

  公开号：US20020028808A1

  公开（公告）日：2002-03-07

  The present invention relates to the use of potassium channel agonists for treating cancer, more particular the treatment and/or prevention of breast cancer and endometrial cancer. The present invention also embraces the use of the compounds of general formulas (I) and (Ia) in treating cancer and methods of using the compounds and their pharmaceutical compositions.

  本发明涉及使用钾通道激动剂治疗癌症，更具体地说是治疗和/或预防乳腺癌和子宫内膜癌。本发明还包括使用一般式(I)和(Ia)的化合物治疗癌症以及使用这些化合物及其药物组合物的方法。
• Use of potassium channel openers for the treatment of insulitis
  申请人：——

  公开号：US20020032193A1

  公开（公告）日：2002-03-14

  The present invention relates to the use of potassium channel agonists for the treatment of insulitis associated with various forms of diabetes such as IDDM, NIDDM, SPIDDM (LADA) and gestational diabetes.

  本发明涉及使用钾通道激动剂治疗与各种形式的糖尿病相关的胰岛炎，如IDDM、NIDDM、SPIDDM（LADA）和妊娠糖尿病。
• 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。