N-对甲基苯磺酰基-2-氯-1,4-萘醌亚胺 | 70249-49-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: N-对甲基苯磺酰基-2-氯-1,4-萘醌亚胺
• 英文名称: N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)-4-methyl benzenesulfonamide
• 英文别名: N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)-4-methylbenzenesulfonamide；N-p-methylbenzenesulfonyl-2-chloro-1,4-naphthoquinone imine；(E)-N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)-4-methylbenzenesulfonamide；N-(3-chloro-4-oxonaphthalen-1-ylidene)-4-methylbenzenesulfonamide
• CAS: 70249-49-9
• 化学式: C₁₇H₁₂ClNO₃S
• 分子量: 345.806
• InChiKey: HEXZPWGZGDGCEG-UHFFFAOYSA-N

物化性质

• 沸点：
  500.4±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  72
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-对甲基苯磺酰基-2-氯-1,4-萘醌亚胺 在 吡啶 、 sodium thiosulfate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.25h， 生成 2-((1-hydroxy-4-((4-methylphenyl)sulfonamido)naphthalen-2-yl)thio)acetic acid
  参考文献：
  名称：

  新型芳香族磺酰基萘基硼酸酯作为20S蛋白酶体抑制剂

  摘要：

  开发了一系列新的非肽蛋白酶体抑制剂（PIs），可作用于蛋白酶体的胰凝乳蛋白酶样（ChT-L）。在初步的生物学活性测试中，这些带有4-芳族磺酰基萘基支架和Leu-硼基作为共价键的PI表现出比PI-8182更好的抑制ChT-L的活性。结果表明，2a中（IC 50  = 6.942μM，MCF-7）和图2c（IC 50  = 6.905μM，MCF-7）显示更高的抗增殖活性要比硼替佐米（IC 50  = 18.37μM，MCF-7）根据我们的实验条件。此外，在微粒体稳定性测定中，2a表现出优异的代谢稳定性，40分钟后剩余56％，而Bortezomib则剩余约30％。化合物2a，2c作为有希望的先导化合物出现，用于开发新型非肽硼酸酯PI。

  DOI：

  10.1016/j.bmc.2018.01.017
• 作为产物：
  描述：

  N-(4-羟基萘-1-基)-4-甲基苯磺酰胺 在 氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66.6%的产率得到N-对甲基苯磺酰基-2-氯-1,4-萘醌亚胺
  参考文献：
  名称：

  Avdeenko, A. P.; Velichko, N. V.; Romanenko, E. A., Journal of Organic Chemistry USSR (English Translation), 1991, vol. 27, # 8, p. 1535 - 1543

  摘要：

  DOI：

文献信息

• PROTEASOME INHIBITORS HAVING CHYMOTRYPSIN-LIKE ACTIVITY
  申请人：Lawrence Harshani

  公开号：US20120142917A1

  公开（公告）日：2012-06-07

  Disclosed herein is the use of HLM-008182, as well as its analogues formed via in-house synthesis, as a potent proteasome inhibitors. A new method was developed for HLM-008182 through a four-step protocol and the method was further optimized to a two step protocol. The synthesis in both protocols was regioselective with TiCl 4 . The reaction was highly efficient with microwave assisted heating and THF as solvent. The modification around the molecule HLM-008182 established primary SAR, indicating that the proteasome inhibition activity was a function of the 2-side chain.

  本文披露了使用HLM-008182及其由内部合成形成的类似物作为有效的蛋白酶体抑制剂。通过四步协议开发了HLM-008182的新方法，并将该方法进一步优化为两步协议。在两种协议的合成中，都使用了TiCl4进行区域选择性反应。微波辅助加热和THF作为溶剂使反应高效。对HLM-008182分子周围的修饰建立了主要的SAR，表明蛋白酶体抑制活性是2侧链的一个功能。
• 10.1039/d4ra03231d
  作者：Liu, Tingting、Wang, Jianbin、Xiao, Rou、Zhao, Junling

  DOI：10.1039/d4ra03231d

  日期：——

  A strategy allowing the switchable divergent synthesis of chiral indole derivatives was established via chiral phosphoric acid-catalyzed asymmetric dearomatization of 2,3-disubstituted indoles using naphthoquinone monoimines as electrophiles. The products were switched between chiral indolenines and fused indolines according to the post-processing conditions. Both two types of products were obtained

  使用萘醌单亚胺作为亲电子试剂，通过手性磷酸催化 2,3-二取代吲哚的不对称脱芳构化，建立了一种可切换不同合成手性吲哚衍生物的策略。根据后处理条件，产物在手性吲哚啉和稠合吲哚啉之间切换。两种类型的产物均以良好至高的产率获得，并且具有优异的对映选择性。人们发现 NaBH 4在形成稠合二氢吲哚的环化过程中充当促进剂和还原剂。
• Discovery of carbazole derivatives as novel allosteric MEK inhibitors by pharmacophore modeling and virtual screening
  作者：Dandan Xi、Yan Niu、Hongyue Li、Stefan M. Noha、Veronika Temml、Daniela Schuster、Chao Wang、Fengrong Xu、Ping Xu

  DOI：10.1016/j.ejmech.2019.06.027

  日期：2019.9

  We report in this work the discovery of novel allosteric MEK inhibitors by pharmacophore modeling and virtual screening. Two out of 13 virtual hit compounds were identified as MEK kinase inhibitors using a MEK1 binding assay. Structural derivations on the hit compound M100 (IC50 = 27.2 +/- 4.5 mu M in RAF-MEK cascading assay) by substituent transformation and bioisosterism replacement have led to the synthesis of a small library of carbazoles. The enzymatic studies revealed the preliminary structure-activity relationships and the derivative 22k (IC50=12.8 +/- 0.5 mu M) showed the most potent inhibitory effect against Raf-MEK cascading. Compound 7 was discovered as toxic as M100 to tumor cells whereas safer to HEK293 cells (IC50 > 100 mu M) than M100 (IC50 = 8.9 +/- 2.0 mu M). It suggests that carbazole is a good scaffold for the design of novel MEK inhibitors for therapeutic uses. More importantly, the developed pharmacophore model can serve as a reliable criterion in novel MEK inhibitor discovery. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Avdeenko, Russian Journal of Organic Chemistry, 1999, vol. 35, # 8, p. 1182 - 1190
  作者：Avdeenko

  DOI：——

  日期：——
• Avdeenko, A. P.; Velichko, N. V.; Tolmachev, A. A., Journal of general chemistry of the USSR, 1990, vol. 60, # 7.1, p. 1339 - 1342
  作者：Avdeenko, A. P.、Velichko, N. V.、Tolmachev, A. A.、Pirozhenko, V. V.、Gol'dfarb, E. I.

  DOI：——

  日期：——