叔-丁基N-(4-溴-2-甲基苯基)氨基甲酸酯 | 319002-53-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 叔-丁基N-(4-溴-2-甲基苯基)氨基甲酸酯
• 英文名称: 3-amino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
• 英文别名: 3-amino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine-1,1-dioxide；6-chloro-1,1-dioxo-4H-thieno[3,2-e][1,2,4]thiadiazin-3-amine
• CAS: 319002-53-4
• 化学式: C₅H₄ClN₃O₂S₂
• 分子量: 237.691
• InChiKey: MJACTUZYFWEGEB-UHFFFAOYSA-N

物化性质

• 熔点：
  >350 °C (decomp)
• 沸点：
  466.1±55.0 °C(Predicted)
• 密度：
  2.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  叔-丁基N-(4-溴-2-甲基苯基)氨基甲酸酯 以 水 、 正丁胺 为溶剂， 以35 mg (57%)的产率得到3-Butylamino-6-chloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
  参考文献：
  名称：

  Novel process

  摘要：

  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。

  公开号：

  US20020119969A1
• 作为产物：
  描述：

  苯乙脒,2,6-二氯-a-羟基- 在 ammonium hydroxide 作用下， 反应 16.0h， 以94%的产率得到叔-丁基N-(4-溴-2-甲基苯基)氨基甲酸酯
  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

• New 3-Alkylamino-4<i>H</i>-thieno-1,2,4-thiadiazine 1,1-Dioxide Derivatives Activate ATP-Sensitive Potassium Channels of Pancreatic Beta Cells
  作者：Flemming E. Nielsen、Søren Ebdrup、Anette Frost Jensen、Lars Ynddal、Thora B. Bodvarsdottir、Carsten Stidsen、Anne Worsaae、Harrie C. M. Boonen、Per O. G. Arkhammar、Tinna Fremming、Philip Wahl、Hanne T. Kornø、J. Bondo Hansen

  DOI：10.1021/jm060042j

  日期：2006.7.1

  Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. Compound 1a inhibits insulin release in vitro and in vivo and preserves beta cell function in preclinical animal models suggesting that such a compound could find use in treatment or prevention of type 1 and type 2 diabetes. The crystal structure and a convergent synthesis of 1a are presented together with a range of new analogues

  化合物1a（NN414）是Kir6.2 / SUR1 K（ATP）通道的有效开启剂。化合物1a抑制胰岛素在体外和体内的释放，并在临床前动物模型中保留β细胞功能，这表明该化合物可用于治疗或预防1型和2型糖尿病。介绍了1a的晶体结构和会聚合成，以及一系列1a的新类似物。有几种化合物，例如6-氯-3-（1-甲基-1-苯乙基）氨基-4H-噻吩并[3,2-e] -1,2,4-噻二嗪1,1-二氧化物（1h）。被发现是有效的Kir6.2 / SUR1 K（ATP）通道的开放剂，并且能够抑制葡萄糖从大鼠胰岛中体外（EC（50）= 0.04 +/- 0.01μM）和静脉内或静脉注射后体内释放的胰岛素口服给予高胰岛素肥胖的Zucker大鼠（ED（50）= 4.0 mg / kg）。