N-benzenesulfonyl-2-chloro-1,4-naphthoquinone imine | 36062-37-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-benzenesulfonyl-2-chloro-1,4-naphthoquinone imine
• 英文别名: N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide；N-(3-chloro-4-oxo-4H-[1]naphthylidene)-benzenesulfonamide；N-(3-Chlor-4-oxo-4H-[1]naphthyliden)-benzolsulfonamid；(E)-N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide；N-(3-chloro-4-oxonaphthalen-1-ylidene)benzenesulfonamide
• CAS: 36062-37-0
• 化学式: C₁₆H₁₀ClNO₃S
• 分子量: 331.779
• InChiKey: UZFYJDSIBAZRIC-UHFFFAOYSA-N

物化性质

• 沸点：
  493.4±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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-benzenesulfonyl-2-chloro-1,4-naphthoquinone imine 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-(phenylsulfonamido)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-hydroxynaphthalen-1-yl)benzenesulfonamide 在 氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66.4%的产率得到N-benzenesulfonyl-2-chloro-1,4-naphthoquinone imine
  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

• Discovery and Synthesis of Hydronaphthoquinones as Novel Proteasome Inhibitors
  作者：Yiyu Ge、Aslamuzzaman Kazi、Frank Marsilio、Yunting Luo、Sanjula Jain、Wesley Brooks、Kenyon G. Daniel、Wayne C. Guida、Saïd M. Sebti、Harshani R. Lawrence

  DOI：10.1021/jm201118h

  日期：2012.3.8

  guided synthesis of more than 170 derivatives revealed that the thioglycolic acid side chain is required and the carboxylic acid group of this side chain is critical to the CT-L inhibitory activity of compound 1. Furthermore, replacement of the carboxylic acid with carboxylic acid isosteres such as tetrazole or triazole greatly improves potency. Compounds with a thio-tetrazole or thio-triazole side chain

  筛选工作导致鉴定出 PI-8182 ( 1 )，蛋白酶体的胰凝乳蛋白酶样 (CT-L) 活性抑制剂。化合物1含有氢萘醌药效基团，其 2 位为巯基乙酸侧链，4 位为噻吩磺酰胺。开发了一种有效的氢萘醌磺酰胺支架合成路线，并在内部合成了化合物1以确认其结构和活性（IC 50 = 3.0 ± 1.6 μM [ n = 25]）。1 的新型氢萘醌衍生物被设计、合成和评估为蛋白酶体抑制剂。超过 170 种衍生物的构效关系 (SAR) 指导合成表明需要巯基乙酸侧链，并且该侧链的羧酸基团对化合物1的 CT-L 抑制活性至关重要。此外，用四唑或三唑等羧酸等排体替代羧酸可大大提高效力。在位置 2 具有硫代四唑或硫代三唑侧链的化合物，其中噻吩被疏水芳基部分取代，是最活跃的化合物，其 CT-L 抑制比化合物1（化合物15e、15f）高 20 倍, 15 小时,图15j，IC 50值在200nM左右，化合物29，IC
• 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。
• Identification of a Novel Family of BRAF^V600E Inhibitors
  作者：Jie Qin、Peng Xie、Christian Ventocilla、Guoqiang Zhou、Adina Vultur、Quan Chen、Qin Liu、Meenhard Herlyn、Jeffrey Winkler、Ronen Marmorstein

  DOI：10.1021/jm3004416

  日期：2012.6.14

  The BRAF oncoprotein is mutated in about half of malignant melanomas and other cancers, and a kinase activating single valine to glutamate substitution at residue 600 (BRAF(V600E)) accounts for over 90% of BRAF-mediated cancers. Several BRAF(V600E) inhibitors have been developed, although they harbor some liabilities, thus motivating the development of other BRAF(V600E) inhibitor options. We report here the use of an ELISA based high-throughput screen to identify a family of related quinolol/naphthol compounds that preferentially inhibit BRAF(V600E) over BRAF(WT) and other kinases. We also report the X-ray crystal structure of a BRAF/quinolol complex revealing the mode of inhibition, employ structure-based medicinal chemistry efforts to prepare naphthol analogues that inhibit BRAF(V600E) in vitro with IC50 values in the 80-200 nM range under saturating ATP concentrations, and demonstrate that these compounds inhibit MAPK signaling in melanoma cells. Prospects for improving the potency and selectivity of these inhibitors are discussed.
• Quinone Imides. III. 1,4-Naphthoquinone Disulfonimides
  作者：Roger Adams、R. A. Wankel

  DOI：10.1021/ja01145a048

  日期：1951.1