7-chloro-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide | 40009-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: 7-chloro-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
• 英文别名: 7-Chloro-3-(methylthio)-4H-benzo[e][1,2,4]thiadiazine 1,1-dioxide；7-chloro-3-methylsulfanyl-4H-1λ6,2,4-benzothiadiazine 1,1-dioxide
• CAS: 40009-41-4
• 化学式: C₈H₇ClN₂O₂S₂
• 分子量: 262.741
• InChiKey: QDRGKNJCWCYIIL-UHFFFAOYSA-N

物化性质

• 熔点：
  287-290 °C
• 沸点：
  458.5±47.0 °C(Predicted)
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  92.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide 在 溴 、 sodium carbonate 作用下， 生成 7-chloro-3-(methylsulfinyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring

  摘要：

  7-氯-3-吡啶基（烷基）氨基-4H-1,2,4-苯并噻二嗪-1,1-二氧化物和3-烷基氨基-7-氯-4H-1,2,4-苯并噻二嗪-1,1-二氧化物，其侧链在3位含有一个或多个杂原子，已经合成，以寻找新的有效的KATP通道开放剂。通过测量它们对胰岛素释放过程的抑制活性，将这些化合物作为潜在的胰岛B细胞KATP通道开放剂进行了测试。讨论了3位侧链性质对生物活性的影响。

  DOI：

  10.1211/0022357011776216
• 作为产物：
  描述：

  7-chloro-2,3-dihydro-3-oxo-4H-1,2,4-benzothiadiazine 在 吡啶 、 tetraphosphorus decasulfide 、 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 生成 7-chloro-3-methylsulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
  参考文献：
  名称：

  Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring

  摘要：

  7-氯-3-吡啶基（烷基）氨基-4H-1,2,4-苯并噻二嗪-1,1-二氧化物和3-烷基氨基-7-氯-4H-1,2,4-苯并噻二嗪-1,1-二氧化物，其侧链在3位含有一个或多个杂原子，已经合成，以寻找新的有效的KATP通道开放剂。通过测量它们对胰岛素释放过程的抑制活性，将这些化合物作为潜在的胰岛B细胞KATP通道开放剂进行了测试。讨论了3位侧链性质对生物活性的影响。

  DOI：

  10.1211/0022357011776216

文献信息

• 1,2,4-benzothiadiazine derivatives, their preparation and use
  申请人：Novo Nordisk AIS

  公开号：US06242443B1

  公开（公告）日：2001-06-05

  1,2,4-Benzothiadiazine derivatives represented by formula wherein D, R1, R2, R3, R4, R5, R12, R13, R14, R15 are defined in the description, composition 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.

  1,2,4-苯并噻二嗪衍生物的化学式如下： 其中D，R1，R2，R3，R4，R5，R12，R13，R14，R15在描述中有定义，描述了其组成以及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、呼吸系统、消化系统和内分泌系统疾病方面具有用途。
• [EN] HALOGENATED BENZOTHIADIAZINES FOR THE TREATMENT OF CANCER<br/>[FR] BENZOTHIADIAZINES HALOGÉNÉES POUR LE TRAITEMENT DU CANCER
  申请人：UNIV NEBRASKA

  公开号：WO2021236818A1

  公开（公告）日：2021-11-25

  Provided herein are compounds and methods for modulating the mitochondrial respiratory complex II (CII) and vascular endothelial growth factor (VEGF) pathways. More particularly, provided are inhibitors of the mitochondrial respiratory complex II (CII) and vascular endothelial growth factor (VEGF) pathways and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer.

  本文提供了一些化合物和方法，用于调节线粒体呼吸链复合物II（CII）和血管内皮生长因子（VEGF）通路。更具体地，提供了线粒体呼吸链复合物II（CII）和血管内皮生长因子（VEGF）通路的抑制剂，以及这些抑制剂在调节疾病和紊乱方面的用途，例如治疗癌症。
• Triphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels
  作者：Céline Constant-Urban、Mounia Charif、Eric Goffin、Jean-Claude Van Heugen、Benaïssa Elmoualij、Patrice Chiap、Ange Mouithys-Mickalad、Didier Serteyn、Philippe Lebrun、Bernard Pirotte、Pascal De Tullio

  DOI：10.1016/j.bmcl.2013.08.091

  日期：2013.11

  target mitochondrial ATP-sensitive potassium channels (mitoKATP channels). An innovative approach should consist in fixing a cationic and hydrophobic triphenylphosphonium fragment on the structure of known KATP channel openers. Such phosphonium salts are expected to cross the biological membranes and to accumulate into mitochondria. Previous works revealed that the presence of an (R)-1-hydroxy-2-propylamino

  本工作旨在确定能够靶向线粒体ATP敏感性钾通道（mitoK ATP通道）的新型离子通道调节剂。一种创新方法应包括将阳离子和疏水性三苯基phosph片段固定在已知的K ATP通道开放剂的结构上。预期此类phospho盐穿过生物膜并积聚到线粒体中。 先前的工作表明，在大多数情况下，在4 H -1,2,4-苯并噻二嗪1,1-二氧化物K ATP通道开放剂的3位上存在（R）-1-羟基-2-丙基氨基链，对胰腺型（SUR1 / Kir6.2）K ATP通道的选择性。为了靶向心脏mitoK ATP通道，我们决定通过SUR1选择性（R）-7-氯-3-（1-羟基-2-丙基）氨基-4 H -1上的酯键引入三苯基phosph基团，2,4-苯并噻二嗪1,1-二氧化物。发现新化合物保留了对胰岛素分泌的抑制活性（SUR1型K ATP通道开放剂），但没有观察到明显的证据表明心肌细胞对线粒体有影响（氧气消耗量，呼吸参数和H
• 3-Piperazinyl 1,2,4-benzothiadiazine 1,1-dioxide derivatives their
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04029780A1

  公开（公告）日：1977-06-14

  A compound of the formula ##STR1## wherein R.sub.1 represents a hydrogen atom or a lower alkyl group, and R.sub.2 represents a hydrogen or halogen atom or a trifluoromethyl group, And its pharmaceutically acceptable salt. The compound is prepared by reacting the corresponding 1,2,4-benzothiadiazine 1,1-dioxide with a piperazine compound or alkylating 1,2,4-benzothiadiazine 1,1-dioxide whose corresponding 3-position is substituted by a piperazinyl group. The above compound has superior antihypertensive activity separated from diuretic, antidiuretic and hyperglycemic activities, and is free from side-effects.

  该化合物的分子式为##STR1##其中R.sub.1代表氢原子或较低的烷基团，R.sub.2代表氢原子或卤素原子或三氟甲基基团，以及其药学上可接受的盐。该化合物是通过将相应的1,2,4-苯并噻二嗪-1,1-二氧化物与哌嗪化合物反应或烷基化相应3位被哌嗪基取代的1,2,4-苯并噻二嗪-1,1-二氧化物而制备的。该化合物具有优越的抗高血压活性，与利尿、抗利尿和高血糖活性分离，且无副作用。
• 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.