噻酮 | 7499-96-9

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 噻酮
• 英文名称: 2-n-butyl-1,1-dioxo-1,2-dihydro-1λ6-benzo[d]isothiazo-3-one
• 英文别名: 2-butyl-1,2-benzisothiazol-3(2H)-one 1,1-dioxide；2-butyl-1,2-benzothiazol-3(2H)-one 1,1-dioxide；N-(n-butyl)saccharin；2-butyl-1,1-dioxo-1λ⁶-benz[d]isothiazol-3-one；2-Butyl-1,1-dioxo-1λ⁶-benz[d]isothiazol-3-on；butyl saccharin；2-Butyl-1,1-dioxo-1,2-benzothiazol-3-one
• CAS: 7499-96-9
• 化学式: C₁₁H₁₃NO₃S
• mdl: MFCD00807755
• 分子量: 239.295
• InChiKey: OVHVVWXDKDMZQA-UHFFFAOYSA-N

物化性质

• 熔点：
  39.5-40.2 °C
• 沸点：
  121-128 °C(Press: 0.06 Torr)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H315,H319,H302

制备方法与用途

噻酮的促渗效果

根据卫生部的规定，一种新型促渗剂需要通过药检试验和促渗效果试验才能申报药号。噻酮在试验中显示出较高的促渗效果，并且药检结果令人满意。

噻酮的促渗机理

噻酮的促渗机理试验显示：当噻酮与红细胞膜作用后，膜结合水的功能下降，导致烃链间的作用明显减弱，从而使脂类分子的刚性降低，增加了膜的流动性。这使得膜更容易破损，通透性增强。由于皮肤脂质层细胞间隙的双分子层与红细胞膜脂质双分子层相似，在试验中出现了使红细胞膜受损溶血的现象。研究结果表明噻酮与氮酮的促渗机理相似。药物在促渗剂的作用下通过透皮吸收过程进入人体：首先透过表皮角质层，然后进入真皮组织，进一步到达皮下脂肪的毛细血管，在毛细血管中被吸收并进入血液循环。如果不使用促渗剂，许多外用药物难以克服皮肤屏障功能而无法实现治疗作用。如今有了促渗剂的帮助，约2/3的药物可以实现透皮吸收给药。

噻酮在医药方面的应用

噻酮经过一系列试验后取得了较为满意的结果，并进行了初步临床试验。选择了7种单独用药效果不明显的疾病（如皮炎、手足癣、股癣、湿疹、痤疮和多发性毛节炎），并加入1%噻酮混入药剂，共有5种不同的剂型（膏剂、霜剂、乳剂、水溶液和贴膏）。试验结果显示，在75个病例中均不同程度地提高了疗效。其中醋酸去炎松软膏治疗湿疹的效果尤为显著，用药后第二天即见明显效果，并且治愈后的皮肤与正常皮肤无异。需要注意的是，在制剂中不得混入凡士林等石油产品，否则会降低甚至完全失去噻酮的促渗效果。

反应信息

• 作为反应物：
  描述：

  噻酮 在 potassium tert-butylate 、 乙酸酐 作用下， 反应 4.58h， 生成 ethyl 2-(2-butyl-1,1-dioxo-1,2-benzothiazol-3-ylidene)-2-cyanoacetate
  参考文献：
  名称：

  Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents

  摘要：

  Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.

  DOI：

  10.1021/jm00102a016
• 作为产物：
  描述：

  saccharin sodium salt 生成 噻酮
  参考文献：
  名称：

  WROEL, JAY E.

  摘要：

  DOI：

文献信息

• TiCl4-Mediated Direct N-Alkylation of Sulfonamides with Inactive Ethers
  作者：Wei Zeng、Jiayan Chen、Ling Dang、Qiang Li、Yong Ye、Shaomin Fu

  DOI：10.1055/s-0031-1290332

  日期：2012.3

  A TiCl4-mediated intermolecular or intramolecular direct N-alkylation reaction of sulfonamides with inactive ethers as alkylating agents was successfully achieved. This method provides a novel approach towards N-alkyl sulfonamides from inactive ethers via an easy workup procedure. N-alkylation - Lewis acid - N-alkyl sulfonamide - dialkyl ether - titanium tetrachloride

  磺酰胺与惰性醚作为烷基化剂的TiCl 4介导的分子间或分子内直接N-烷基化反应已成功实现。该方法提供了一种通过简单的后处理程序从惰性醚制备N-烷基磺酰胺的新颖方法。 N-烷基化-路易斯酸-N-烷基磺酰胺-二烷基醚-四氯化钛
• Decarbonylative CC Bond-Forming Reactions of Saccharins by Nickel Catalysis: Homocoupling and Cycloaddition
  作者：Pengbing Mi、Peiqiu Liao、Tao Tu、Xihe Bi

  DOI：10.1002/chem.201406227

  日期：2015.3.27

  Decarbonylation of saccharins by nickel catalysis enables two kinds of CC bond‐forming reactions; homocoupling of saccharins to form biaryls and cycloaddition with alkynes to form benzosultams. The former represents the first reported nickel‐catalyzed decarbonylative CC homocoupling reaction, whereas the latter constitutes a powerful method to pharmaceutically relevant benzosultams. The reactions proceed with

  镍催化糖精脱羰可实现两种CC键形成反应。糖精均相偶联形成联芳基，与炔烃加成环合形成苯并阿磺酰胺。前者代表首次报道镍催化decarbonylativeÇ  Ç自偶联反应，而后者构成了有力的方法来药物相关benzosultams。反应进行时具有良好的官能团耐受性和出色的区域选择性。
• Hypolipidemic activity of phthalimide derivatives. 3. A comparison of phthalimide and 1,2-benzisothiazolin-3-one 1,1-dioxide derivatives to phthalimidine and 1,2-benzisothiazoline 1,1-dioxide congeners
  作者：James M. Chapman、George H. Cocolas、Iris H. Hall

  DOI：10.1021/jm00356a023

  日期：1983.2

  ne 1,1-dioxide analogues for their hypolipidemic activity in mice and to compare them to their respective phthalimide congeners. In addition, a series of 1,2-benzisothiazoline 1,1-dioxide and phthalimidine analogues was prepared, and their hypolipidemic activity was compared to the phthalimide analogues. These studies show that the respective congeners of 1,2-benzisothiazolin-3-one 1,1-dioxide compared

  以前已经观察到链长为四个碳或氧原子的N-取代的邻苯二甲酰亚胺衍生物在啮齿动物中以20（mg / kg）/天ip的剂量表现出有效的降血脂活性。还观察到1,2-苯并噻唑啉-3-一1,1-二氧化物（糖精）核本身在相同剂量下具有活性。进行了一项研究，以检查一系列1,2-苯并噻唑啉-3-酮1,1-二氧化物类似物在小鼠中的降血脂活性，并将它们与各自的邻苯二甲酰亚胺同系物进行比较。此外，制备了一系列1,2-苯并噻唑啉1,1-二氧化物和邻苯二甲酰亚胺类似物，并将它们的降血脂活性与邻苯二甲酰亚胺类似物进行了比较。这些研究表明1,2-苯并噻唑啉-3-酮1，1-二氧化物在减少20（mg / kg）/天ip的雄性CF1小鼠血清甘油三酸酯和胆固醇水平方面优于邻苯二甲酰亚胺同类物。在糖精衍生物中，3-氧-1,2-苯并噻唑啉-2-丙酸1,1-二氧化物最有效地降低16天服药后的血清胆固醇水平53％，3-氧-1,2-苯并噻唑啉服用14天后，-2-戊酸1
• N -Substituted and ring opened saccharin derivatives selectively inhibit transmembrane, tumor-associated carbonic anhydrases IX and XII
  作者：Jekaterīna Ivanova、Fabrizio Carta、Daniela Vullo、Janis Leitans、Andris Kazaks、Kaspars Tars、Raivis Žalubovskis、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2017.04.007

  日期：2017.7

  well as some ring opened derivatives were prepared and investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The widespread cytosolic isoforms CA I and II were not inhibited by these sulfonamides whereas transmembrane, tumor-associated ones were effectively inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA XII. Although the inhibition mechanism

  制备了一系列结合有芳基，烷基和炔基部分的N-取代糖精，以及一些开环衍生物，并作为金属酶碳酸酐酶的抑制剂进行了研究（CA，EC 4.2.1.1）。这些磺胺类药物不会抑制广泛的胞质亚型CA I和II，而与肿瘤相关的跨膜被有效抑制，CA IX的KIs范围为22.1-481nM，hCA XII的KIs范围为3.9-245nM。尽管目前尚不清楚这些叔/仲磺酰胺的抑制机制，但是对于抑制与胞质广泛分布的同工型相关的肿瘤的良好疗效，尤其是选择性，使得这些衍生物作为酶抑制剂具有相当大的兴趣，并具有多种药理应用。
• Regioselective Alkylation of Saccharin with Alcohols under Mitsunobu Conditions
  作者：Xiaolong Wang、Yanying Ma、Tingting Ju

  DOI：10.3184/174751913x13716447161975

  日期：2013.7

  The regioselective Mitsunobu alkylation of saccharin with various alcohols has been examined. The N/O-alkylation is dependent on the steric hindrance of the alcohols, that is, less sterically hindered alcohol preferentially afford N-alkylated saccharin and vice versa.

  已经研究了糖精与各种醇的区域选择性 Mitsunobu 烷基化。N/O-烷基化取决于醇的空间位阻，即空间位阻较小的醇优先提供N-烷基化糖精，反之亦然。