N-(3-amino-5-chlorothien-2-yl)sulfonyl-N'-hexylthiourea

• 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: N-(3-amino-5-chlorothien-2-yl)sulfonyl-N'-hexylthiourea
• 英文别名: 1-(3-Amino-5-chlorothiophen-2-yl)sulfonyl-3-hexylthiourea
• 化学式: C₁₁H₁₈ClN₃O₂S₃
• 分子量: 355.934
• InChiKey: UHYDPSFJTSWBKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-amino-5-chlorothien-2-yl)sulfonyl-N'-hexylthiourea 在 光气 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.0h， 以33%的产率得到6-chloro-3-hexylamino-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
• 作为产物：
  描述：

  异硫氰酸己酯 、 3-amino-5-chlorothiophene-2-sulfonamide hydrochloride 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.67h， 以72%的产率得到N-(3-amino-5-chlorothien-2-yl)sulfonyl-N'-hexylthiourea
  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

• 6-Chloro-3-alkylamino-4<i>H</i>-thieno[3,2<i>-e</i>]-1,2,4-thiadiazine 1,1-Dioxide Derivatives Potently and Selectively Activate ATP Sensitive Potassium Channels of Pancreatic β-Cells
  作者：Flemming E. Nielsen、Thora B. Bodvarsdottir、Anne Worsaae、Peter MacKay、Carsten E. Stidsen、Harrie C. M. Boonen、Lone Pridal、Per O. G. Arkhammar、Philip Wahl、Lars Ynddal、Finn Junager、Nils Dragsted、Tina M. Tagmose、John P. Mogensen、Anette Koch、Svend P. Treppendahl、J. Bondo Hansen

  DOI：10.1021/jm0208121

  日期：2002.9.1

  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.