2-(4-nitrobenzyl)-1,2-benzothiazol-3(2H)-one 1,1-dioxide | 41335-46-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-(4-nitrobenzyl)-1,2-benzothiazol-3(2H)-one 1,1-dioxide
• 英文别名: (4-nitrobenzyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide；N-(4-nitrobenzyl)-1,2-benzisothiazole-1,1-dioxide-3-one；2-(4-nitro-benzyl)-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[d]isothiazol-3-one；2-(4-nitro-benzyl)-1,1-dioxo-1λ⁶-benz[d]isothiazol-3-one；2-(4-Nitro-benzyl)-1,1-dioxo-1λ⁶-benz[d]isothiazol-3-on；N-(p-Nitrobenzyl)saccharin；2-[(4-Nitrophenyl)methyl]-2,3-dihydro-1lambda6,2-benzothiazole-1,1,3-trione；2-[(4-nitrophenyl)methyl]-1,1-dioxo-1,2-benzothiazol-3-one
• CAS: 41335-46-0
• 化学式: C₁₄H₁₀N₂O₅S
• 分子量: 318.31
• InChiKey: FEEPYZGZJFLONU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-nitrobenzyl)-1,2-benzothiazol-3(2H)-one 1,1-dioxide 在 potassium tert-butylate 、 乙酸酐 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 生成 Ethyl 2-cyano-2-[3-cyano-2-[(4-nitrophenyl)methyl]-1,1-dioxo-1,2-benzothiazol-3-yl]acetate
  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：

  糖精 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-nitrobenzyl)-1,2-benzothiazol-3(2H)-one 1,1-dioxide
  参考文献：
  名称：

  开放的基于糖精的仲磺酰胺可作为与癌症相关的碳酸酐酶IX和XII亚型的有效和选择性抑制剂。

  摘要：

  合成了大量基于开放糖精支架的新型仲磺酰胺，并将其评估为人类碳酸酐酶的四种不同同工型的选择性抑制剂（hCA I，II，IX和XII，EC 4.2.1.1）。它们是通过新合成的N-烷基化糖精衍生物的还原性开环获得的，并且显示出对两种胞质脱靶hCA I和II（Kis> 10 µM）无活性。有趣的是，这些化合物在低纳摩尔范围内抑制hCA IX，Kis在20至298 nM之间，并且是hCA XII同工酶的极强抑制剂（Kis在4.3至432 nM之间）。由于hCA IX和XII是最近被证实可作为药物靶标的与癌症相关的亚型，因此这些结果代表了开发新的抗癌候选药物的重要目标。最后，

  DOI：

  10.1080/14756366.2016.1235040

文献信息

• A novel library of saccharin and acesulfame derivatives as potent and selective inhibitors of carbonic anhydrase IX and XII isoforms
  作者：Simone Carradori、Daniela Secci、Celeste De Monte、Adriano Mollica、Mariangela Ceruso、Atilla Akdemir、Anatoly P. Sobolev、Rossella Codispoti、Federica De Cosmi、Paolo Guglielmi、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2016.01.038

  日期：2016.3

  Small libraries of N-substituted saccharin and N-/O-substituted acesulfame derivatives were synthesized and tested as atypical and selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). Most of them inhibited hCA XII in the low nanomolar range, hCA IX with KIs ranging between 19 and 2482 nM, whereas they were poorly active against hCA II (KIs

  合成了小的N-取代的糖精和N- / O-取代的乙酰磺胺衍生物文库，并作为人类碳酸酐酶的四种不同同工型（hCA I，II，IX和XII，EC 4.2.1.1）的非典型和选择性抑制剂进行了测试。他们中的大多数在低纳摩尔范围内抑制hCA XII，hCA IX的K I在19和2482 nM之间，而对hCA II（K I s> 10μM）和hCA I（K I范围介于318 nM和50μM之间。由于hCA I和II是普遍存在的脱靶同工型，而癌症相关的同工型hCA IX和XII最近已被验证为药物靶标，因此这些结果在开发新的抗癌候选药物中取得了令人鼓舞的成就。此外，这些抑制剂的结构中缺乏经典的锌结合基团为不同的抑制机制开启了创新的，尚未探索的场景，这可能解释了高抑制选择性。已经进行了一种计算方法以进一步合理化生物学数据并表征这些抑制剂中某些抑制剂的结合模式。
• 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。
• Eckenroth; Koerppen, Chemische Berichte, 1896, vol. 29, p. 1049
  作者：Eckenroth、Koerppen

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