6-chloro-3-fluoro-4H-thieno-[3,2-e]-1,2,4-thiadiazine 1,1-dioxide | 279215-55-3

• 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-fluoro-4H-thieno-[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
• 英文别名: 6-chloro-3-fluoro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide；6-chloro-3-fluoro-4H-thieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide
• CAS: 279215-55-3
• 化学式: C₅H₂ClFN₂O₂S₂
• 分子量: 240.666
• InChiKey: NNDCZYWFMBYQFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 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：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-甲基环丙胺盐酸盐 、 6-chloro-3-fluoro-4H-thieno-[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 21.0h， 以54%的产率得到6-氯-3-((1-甲基环丙基)氨基)-4H-噻吩并(3,2-e)-1,2,4-噻二嗪 1,1-二氧化物
  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：

  苯乙脒,2,6-二氯-a-羟基- 在 potassium fluoride 、 十六烷基三甲基溴化铵 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 20.0h， 生成 6-chloro-3-fluoro-4H-thieno-[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
  参考文献：
  名称：

  新的3-烷基氨基-4H-噻吩并1,2,4-噻二嗪1,1-二氧化物衍生物可激活胰腺β细胞的ATP敏感性钾通道。

  摘要：

  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）。

  DOI：

  10.1021/jm060042j

文献信息

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

  公开号：US06329367B1

  公开（公告）日：2001-12-11

  The present invention relates to 4H-thieno[3,2-e]-1,2,4-thiadiazine derivatives of the general formula: wherein X, Y, R1, R2 and R3 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 endocrinological system.

  本发明涉及通式为4H-噻吩[3,2-e]-1,2,4-噻二嗪衍生物的化合物，其中X、Y、R1、R2和R3在描述中有定义，描述了这些化合物的组合物和制备方法。这些化合物在治疗中枢神经系统、心血管系统、肺部系统、消化系统和内分泌系统疾病中具有用途。
• Fused 1,2,4-Thiadiazine derivatives, their preparation and use
  申请人：NOVO NORDISK A/S

  公开号：EP1338600A1

  公开（公告）日：2003-08-27

  The present invention relates to 4H-thieno[3,2-e]-1,2,4-thiadiazine derivatives, compositions thereof and methods for preparing the compounds. 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 endocrinological system.

  本发明涉及4H-噻吩[3,2-e]-1,2,4-噻二嗪衍生物、其组成物及制备该化合物的方法。该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。
• Fused 1,2,4- thiadiazine derivatives, their preparation and use
  申请人：——

  公开号：US20020086861A1

  公开（公告）日：2002-07-04

  The present invention relates to 4H-thieno[3,2-e]-1,2,4-thiadiazine derivatives of the general formula: 1 wherein X, Y, R 1 , R 2 and R 3 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 endocrinological system.

  本发明涉及4H-噻吩[3,2-e]-1,2,4-噻二嗪衍生物的一般式：1其中X、Y、R1、R2和R3在说明书中定义，描述了它们的组合物和制备该化合物的方法。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的疾病方面有用。
• FUSED 1,2,4-THIADIAZINE DERIVATIVES, THEIR PREPARATION AND USE
  申请人：NOVO NORDISK A/S

  公开号：EP1140945B1

  公开（公告）日：2003-06-04
• US6329367B1
  申请人：——

  公开号：US6329367B1

  公开（公告）日：2001-12-11