4-methyl-3-methylsulfanyl-4H-pyrido<4.3-e>-1,2,4-thiadiazine 1,1-dioxide | 174676-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-methyl-3-methylsulfanyl-4H-pyrido<4.3-e>-1,2,4-thiadiazine 1,1-dioxide
• 英文别名: 4-methyl-3-(methylthio)-4H-pyrido<4,3-e>-1,2,4-thiadiazine 1,1-dioxide；Goshskkvzhduhs-uhfffaoysa-；4-methyl-3-methylsulfanylpyrido[4,3-e][1,2,4]thiadiazine 1,1-dioxide
• CAS: 174676-47-2
• 化学式: C₈H₉N₃O₂S₂
• 分子量: 243.31
• InChiKey: GOSHSKKVZHDUHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  96.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  仲丁胺 、 4-methyl-3-methylsulfanyl-4H-pyrido<4.3-e>-1,2,4-thiadiazine 1,1-dioxide 反应 1.0h， 以67%的产率得到N-butan-2-yl-4-methyl-1,1-dioxopyrido[4,3-e][1,2,4]thiadiazin-3-imine
  参考文献：
  名称：

  3- and 4-Substituted 4H-Pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers:  Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships

  摘要：

  4-N-Subsituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alkyl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure-activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K-ATP channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K-ATP channels (''pancreatic-like'' K-ATP channels) in other tissues.

  DOI：

  10.1021/jm9500582
• 作为产物：
  描述：

  4-methyl-3-oxo-2,3-dihydro-4H-pyrido<4,3-e>-1,2,4-thiadiazine 1,1-dioxide 在 吡啶 、 diphosphorus pentasulfide 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 48.5h， 生成 4-methyl-3-methylsulfanyl-4H-pyrido<4.3-e>-1,2,4-thiadiazine 1,1-dioxide
  参考文献：
  名称：

  3- and 4-Substituted 4H-Pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers:  Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships

  摘要：

  4-N-Subsituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alkyl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure-activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K-ATP channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K-ATP channels (''pancreatic-like'' K-ATP channels) in other tissues.

  DOI：

  10.1021/jm9500582

文献信息

• Synthesis and structural studies of 3-Alkylamino-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides: a new class of heterocyclic compounds with therapeutical promises
  作者：Pascal de Tullio、Raogo Ouedraogo、Léon Dupont、Fabian Somers、Stéphane Boverie、Jean-Michel Dogné、Jacques Delarge、Bernard Pirotte

  DOI：10.1016/s0040-4020(99)00231-8

  日期：1999.4

  3-e]-1,2,4-thiadiazine 1,1-dioxide represents a new class of heterocyclic compounds expressing important pharmacological properties. According to the position of the CN double bond in the thiadiazine ring, this heterocyclic ring system may exist under three different tautomeric forms. By means of spectral and X-ray data collected from selected compounds, the most favourable tautomeric form adopted by

  3-烷基氨基-吡啶并[4,3- e ] -1,2,4-噻二嗪1,1-二氧化物代表了一类新的表达重要药理特性的杂环化合物。根据噻二嗪环中CN双键的位置，该杂环系统可能以三种不同的互变异构形式存在。通过从选定化合物中收集的光谱和X射线数据，最有利的互变异构形式被3-烷基氨基-吡啶并[4,3 - e ] -1,2,4-噻二嗪1,1-二氧化物不含烷基确定2-或4-位的取代基。考虑到这类杂环化合物的药理学潜力，本研究提供有关吡啶并噻二嗪二氧化物的几何和构象方面的新见解是重要的。
• 3- and 4-Substituted 4<i>H</i>-Pyrido[4,3-<i>e</i>]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers:  Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships
  作者：Pascal de Tullio、Bernard Pirotte、Philippe Lebrun、Jeanine Fontaine、Léon Dupont、Marie-Hélène Antoine、Raogo Ouedraogo、Smail Khelili、Carine Maggetto、Bernard Masereel、Ousmane Diouf、Tchao Podona、Jacques Delarge

  DOI：10.1021/jm9500582

  日期：1996.1.1

  4-N-Subsituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alkyl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure-activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K-ATP channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K-ATP channels (''pancreatic-like'' K-ATP channels) in other tissues.