5-imino-4-methyl-2-sulfonamido-δ²-1,3,4-thiadiazoline hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-imino-4-methyl-2-sulfonamido-δ²-1,3,4-thiadiazoline hydrochloride
• 英文别名: hydrochloride salt of 5-imino-4-methyl-Δ²-1,3,4-thiadiazoline-2-sulfonamide；5-imino-4-methyl-Δ²-1,3,4-thiadiazoline-2-sulfonamide hydrochloride；5-Imino-4-methyl-1,3,4-thiadiazole-2-sulfonamide;hydrochloride；5-imino-4-methyl-1,3,4-thiadiazole-2-sulfonamide;hydrochloride
• 化学式: C₃H₆N₄O₂S₂*ClH
• 分子量: 230.699
• InChiKey: BFFYETYVFZIOHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.8
• 重原子数：
  12.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  102.95
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-imino-4-methyl-2-sulfonamido-δ²-1,3,4-thiadiazoline hydrochloride 在 sodium hydroxide 作用下， 生成 5-亚氨基-4-甲基-4,5-二氢-1,3,4-噻二唑-2-磺酰胺
  参考文献：
  名称：

  1,3,4-Thiadiazole- and Thiadiazolinesulfonamides as Carbonic Anhydrase Inhibitors. Synthesis and Structural Studies

  摘要：

  DOI：

  10.1021/ja01599a033
• 作为产物：
  描述：

  醋甲唑胺 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以800 mg的产率得到5-imino-4-methyl-2-sulfonamido-δ²-1,3,4-thiadiazoline hydrochloride
  参考文献：
  名称：

  甲唑胺在人血浆和红细胞中的时程和分布。

  摘要：

  用GLC质谱法测定血浆，全血和尿液中的甲唑胺。单次和多次口服该药物后，血浆和红细胞中的甲唑酰胺浓度呈时间变化模式。从血浆和红细胞浓度的比较可以明显看出，药物与红细胞碳酸酐酶结合的非线性。药物从红细胞中缓慢清除。由血浆和红细胞浓度确定与碳酸酐酶的两种同工酶的结合常数，并与先前的测定结果一致。消除的半衰期为7.5小时。未改变药物的尿回收率约为给药剂量的25％。

  DOI：

  10.1002/jps.2600700115

文献信息

• Carbonic anhydrase inhibitors: aromatic and heterocyclic sulfonamides incorporating adamantyl moieties with strong anticonvulsant activity
  作者：Marc A Ilies、Bernard Masereel、Stéphanie Rolin、Andrea Scozzafava、Gheorghe Câmpeanu、Valentin Cı̂mpeanu、Claudiu T Supuran

  DOI：10.1016/j.bmc.2004.03.008

  日期：2004.5

  A series of aromatic/heterocyclic sulfonamides incorporating adamantyl moieties were prepared by reaction of aromatic/heterocyclic aminosulfonamides with the acyl chlorides derived from adamantyl-1-carboxylic acid and 1-adamantyl-acetic acid. Related derivatives were obtained from the above-mentioned aminosulfonamides with adamantyl isocyanate and adamantyl isothiocyanate, respectively. Some of these

  通过使芳族/杂环氨基磺酰胺与衍生自金刚烷基-1-羧酸和1-金刚烷基乙酸的酰氯反应，制备了一系列结合有金刚烷基部分的芳族/杂环磺酰胺。从上述氨基磺酰胺分别与金刚烷基异氰酸酯和金刚烷基异硫氰酸酯获得相关的衍生物。这些衍生物中的一些对与重要的生理过程有关的两种人CA同功酶CA I和CA II表现出良好的抑制效力，其数量级与临床使用的药物乙酰唑胺和甲唑酰胺相同。确定了最佳CA抑制剂的亲脂性，并表示为它们的实验log k'IAM和理论ClogP值。它们的亲脂性有利于血脑屏障的穿越（log k'> IAM> 1.35）。此处报道的一些最佳CA抑制剂的抗惊厥活性已在小鼠的MES测试中进行了评估。腹膜内注射（30 mg kg（-1））后，化合物A8和A9表现出对电诱发惊厥的高保护作用（> 90％）。ED50分别为3.5和2.6 mg kg（-1）。
• (R)-/(S)-10-Camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases
  作者：Alfonso Maresca、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2011.01.050

  日期：2011.3

  A series of aromatic and heterocyclic sulfonamides incorporating R- and S-camphorsulfonyl moieties were synthesized and investigated for the inhibition of several mammalian isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The new sulfonamides selectively inhibited the mitochondrial isozymes hCA VA and VB (h = human isoform) over the cytosolic, off-target ones hCA I and II, with inhibition

  合成了一系列结合有R-和S-樟脑磺酰基部分的芳香族和杂环磺酰胺，并研究了它们对锌酶碳酸酐酶的几种哺乳动物同工型的抑制作用（CA，EC 4.2.1.1）。新的磺酰胺类药物选择性抑制线粒体同工酶hCA VA和VB（h  =人同工型），超过了细胞质的脱靶hCA I和II，抑制常数在低纳摩尔范围内。取代磺酰胺支架的基团的手性和位置极大地影响了CA的抑制性能。这些化合物是设计针对参与脂肪形成和肥胖症的线粒体CA的同工型选择性酶抑制剂的极好线索。
• Supuran, Claudiu T., Revue Roumaine de Chimie, 1995, vol. 40, # 7-8, p. 643 - 652
  作者：Supuran, Claudiu T.

  DOI：——

  日期：——
• Carbonic anhydrase inhibitors: sulfonamides incorporating furan-, thiophene- and pyrrole-carboxamido groups possess strong topical intraocular pressure lowering properties as aqueous suspensions
  作者：Monica Ilies、Claudiu T. Supuran、Andrea Scozzafava、Angela Casini、Francesco Mincione、Luca Menabuoni、Miron T. Caproiu、Maria Maganu、Mircea D. Banciu

  DOI：10.1016/s0968-0896(00)00143-7

  日期：2000.8

  Important physiological and physio-pathological functions are played by several carbonic anhydrase (CAI EC 4.2.1.1) isozymes, which are strongly inhibited by aromatic and heterocyclic sulfonamides. Here we report several new types of such sulfonamides, incorporating furan-, thiophene- and pyrrole-carboxamide moieties in their molecules. Some of these compounds showed very good CA II and CA IV inhibitory properties, with affinities for the enzymes in the low nanomolar range. Due to their relatively low water solubility, some of the most active CA II inhibitors reported here have been formulated as aqueous suspension for topical administration as antiglaucoma agents, in normotensive and glaucomatous rabbits. The derivatives incorporating furan- and pyrrole-carboxamide moieties (but not the corresponding thiophene-substituted derivatives), showed effective and long-lasting intraocular pressure (IOP) lowering both in normotensive as well as glaucomatous animals, with potencies superior to dorzolamide and brinzolamide, the two available topically acting sulfonamide drugs. This is the first example of non-water soluble sulfonamides that significantly lower IOP, being thus similar with the recently introduced drug brinzolamide, which belongs to a completely different chemical family of antiglaucoma sulfonamides. (C) 2000 Elsevier Science Ltd, All rights reserved.
• 5-thiocarbamylimino-4-substituted-delta2-1,3,4-thiadiazoline-2-sulfonamides
  申请人：AMERICAN CYANAMID CO

  公开号：US02820794A1

  公开（公告）日：1958-01-21