6-chloro-3-octylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide

• 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-octylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
• 英文别名: 6-Chloro-3-octylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide；6-chloro-N-octyl-1,1-dioxo-4H-thieno[3,2-e][1,2,4]thiadiazin-3-imine
• 化学式: C₁₃H₂₀ClN₃O₂S₂
• 分子量: 349.906
• InChiKey: OECJBGOUFZZDJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-硫代异氰酸辛酯 在 光气 、 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 6-chloro-3-octylamino-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：US20040010142A1

  公开（公告）日：2004-01-15

  The present invention relates to a novel processes for preparing pharmaceutically active compounds of formula (I): 1 wherein A and X are defined in the description.

  本发明涉及一种制备具有化学式(I)的药用活性化合物的新型工艺：其中A和X在描述中有定义。
• 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 agonists for reducing fat food consumption
  申请人：——

  公开号：US20020035106A1

  公开（公告）日：2002-03-21

  The present invention relates to the use of potassium channel agonists for reducing or lowering the consumption of fat food. The present invention also embraces the use of the compounds of general formulas (I) and (Ia) in reducing or lowering the intake of fat food and methods of using the compounds and their pharmaceutical compositions.

  本发明涉及使用钾通道激动剂减少或降低脂肪食物的摄入量。本发明还包括通式（I）和（Ia）化合物在减少或降低脂肪食物摄入量方面的用途，以及使用这些化合物及其药物组合物的方法。
• Use of selective potassium channel openers
  申请人：——

  公开号：US20030125323A1

  公开（公告）日：2003-07-03

  The present invention relates to a use of SUR1/Kir6.2 selective potassium channel openers for the preparation of a pharmaceutical composition for the prevention or the treatment of diabetes, and for the treatment of hyperinsulinaemia and hyperandrogenism in women with Polycystic Ovary Syndrome (PCOS) as well as a pharmaceutical composition for use in the prevention or the treatment of diabetes, and in the treatment of hyperinsulinaemia and hyperandrogenism in women with Polycystic Ovary Syndrome.

  本发明涉及利用 SUR1/Kir6.2 选择性钾通道开放剂制备一种药物组合物，用于预防或治疗糖尿病，以及治疗多囊卵巢综合征（PCOS）女性患者的高胰岛素血症和高雄激素症，还涉及一种药物组合物，用于预防或治疗糖尿病，以及治疗多囊卵巢综合征女性患者的高胰岛素血症和高雄激素症。