4-[(4-氯苯甲酰基)氨基]苯磺酰氯 | 89565-15-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[(4-氯苯甲酰基)氨基]苯磺酰氯
• 英文名称: 4-(4-chlorobenzamido)benzenesulfonyl chloride
• 英文别名: 4-(4-Chloro-benzoylamino)-benzenesulfonyl chloride；4-(4-Chlorobenzamido)benzene-1-sulfonyl chloride；4-[(4-chlorobenzoyl)amino]benzenesulfonyl chloride
• CAS: 89565-15-1
• 化学式: C₁₃H₉Cl₂NO₃S
• 分子量: 330.191
• InChiKey: VQKGBQWAZKTZKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(4-氯苯甲酰基)氨基]苯磺酰氯 在 一水合肼 作用下， 以60%的产率得到4-Chloro-N-[4-(hydrazinesulfonyl)phenyl]benzamide
  参考文献：
  名称：

  Cremlyn, R. J.; Swinbourne, F. S.; Batchelor, A., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1983, vol. 22, # 10, p. 1029 - 1043

  摘要：

  DOI：
• 作为产物：
  描述：

  对氨基苯磺酸 在 草酰氯 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-[(4-氯苯甲酰基)氨基]苯磺酰氯
  参考文献：
  名称：

  Design, synthesis and biological evaluation of suramin-derived dual antagonists of the proinflammatory G protein-coupled receptors P2Y2 and GPR17

  摘要：

  Dual- or multi-target drugs are particularly promising for the treatment of complex diseases such as (neuro)inflammatory disorders. In the present study, we identified dual antagonists for two related proinflammatory G protein-coupled receptors (GPCRs), the purinergic receptor P2Y(2) receptor, and the orphan receptor GPR17. Based on the lead compound suramin small molecules were designed, synthesized, and modified, including benzenesulfonate, benzenesulfonamide, dibenzamide and diphenylurea derivatives. Structure-activity relationship studies identified 3-nitrophenyl 4-benzamidobenzenesulfonic acid derivatives as dual P2Y(2)R/GPR17 antagonists. In particular, 3-nitrophenyl 4-(4-chlorobenzamido) benzenesulfonate (14l, IC50 3.01 mu M at P2Y(2)R, and 3.37 mu M at GPR17) and 3-nitrophenyl-4-(2-chlorobenzamido)benzenesulfonate (14m, IC50 3.17 mu M at P2Y(2)R, and 1.67 mu M at GPR17) exhibited dual antagonistic activity. Compound 14l was shown to act as an allosteric antagonist at both receptors. In addition, GPR17-selective antagonists were identified( )including 3-nitrophenyl 4-benzamidobenzenesulfonate (14a, IC50 3.20 mu M) and 3-nitrophenyl 4-(3-(trifluoromethyl)benzamido) benzenesulfonate (14f, IC50 3.88 mu M). The developed antagonists were selective versus other closely related P2Y receptors. They were found to possess high chemical and metabolic stability in human liver microsomes and therefore present good starting points for developing potent multi-target drugs with potential applications in inflammatory diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111789

文献信息

• Design, Synthesis, and Pharmacological Activity of a New Matrix Metalloproteinase-9 Inhibitor
  作者：O. S. Grigorkevich、G. V. Mokrov、A. S. Dyabina、V. N. Stolyaruk、I. B. Tsorin、E. O. Ionova、S. A. Kryzhanovskii、T. A. Gudasheva、A. D. Durnev

  DOI：10.1007/s11094-018-1761-1

  日期：2018.4

  The new MMP-9 inhibitor 1-4-[(4-chlorobenzoyl)amino]phenyl}sulfonyl-L-proline, with a theoretical inhibition constant of IC50 = 4 × 105 M, was constructed on the basis of structural requirements for selective inhibitors of gelatinases. This constructed compound and its close structural analogs were synthesized and these substances were found to have low toxicity, (LD50 > 300 mg/kg). The new inhibitor given p.o. at a dose of 20 mg/kg/day on the background of acute myocardial infarction significantly decreased the content of immunoreactive MMP-9 in plasma in rats, to the level obtained with doxycycline.

  新型MMP-9抑制剂1-4-[(4-氯苯甲酰)氨基]苯基}磺酰-L-脯氨酸的理论抑制常数IC50 = 4 × 105 M，是根据明胶酶选择性抑制剂的结构要求构建的。该化合物及其结构相似的化合物被合成，这些物质被发现具有低毒性（LD50> 300 mg/kg）。在急性心肌梗死的基础上，以20 mg/kg/天的剂量口服新型抑制剂，可显著降低大鼠血浆中免疫反应性MMP-9的含量，达到强力霉素的水平。
• Discovery of TP0597850: A Selective, Chemically Stable, and Slow Tight-Binding Matrix Metalloproteinase-2 Inhibitor with a Phenylbenzamide–Pentapeptide Hybrid Scaffold
  作者：Tomoki Takeuchi、Yusaku Nomura、Tomoko Tamita、Rie Nishikawa、Hiroyuki Kakinuma、Naoki Kojima、Kosuke Hitaka、Yunoshin Tamura、Masafumi Kamitani、Masashi Mima、Akiko Nozoe、Masato Hayashi

  DOI：10.1021/acs.jmedchem.2c01698

  日期：2023.1.12

  discovery of a novel MMP2-selective inhibitor with high chemical stability and slow tight-binding features. Based on the degradation mechanism of our small-molecule–peptide hybrid 1, the tripeptide linker 5-aminopentanoic acid [Ape(5)]–Glu–Asp} of 1 was replaced by a shorter linker (γ-D-Glu). Phenylbenzamide was suitable for the new generation of MMP2 inhibitors as an S1′ pocket-binding group. The

  基质金属蛋白酶 2 (MMP2) 是一种锌依赖性内肽酶，是癌症和纤维化等多种疾病的有希望的靶点。在此，我们报告了一种新型 MMP2 选择性抑制剂的发现，该抑制剂具有高化学稳定性和缓慢的紧密结合特性。基于我们的小分子-肽杂化物1的降解机制，1的三肽接头 5-氨基戊酸 [Ape(5)]–Glu–Asp}被更短的接头 (γ-D-Glu) 取代。苯基苯甲酰胺适合作为新一代 MMP2 抑制剂的 S1' 口袋结合基团。(4 S )-氨基脯氨酸的引入显着提高了化学稳定性，同时由于其与 Glu130 的相互作用而保持了高亚型选择性。TP0597850 ( 18) 在广泛的 pH 值范围内表现出高稳定性以及有效的 MMP2 抑制 ( K i = 0.034 nM) 和使用抑制常数确定的 ≥ 2000 倍选择性。动力学分析表明它具有缓慢的紧密结合性质和较长的 MMP2 解离半衰期 ( t 1/2 = 265
• CREMLYN, R. J.;SWINBOURNE, F. J.;BATCHELOR, A.;HONEYMAN, R.;NASH, D.;SHOD+, INDIAN J. CHEM., 1983, 22, N 10, 1029-1043
  作者：CREMLYN, R. J.、SWINBOURNE, F. J.、BATCHELOR, A.、HONEYMAN, R.、NASH, D.、SHOD+

  DOI：——

  日期：——
• Design, synthesis and biological evaluation of suramin-derived dual antagonists of the proinflammatory G protein-coupled receptors P2Y2 and GPR17
  作者：Thanigaimalai Pillaiyar、Mario Funke、Haneen Al-Hroub、Stefanie Weyler、Sabrina Ivanova、Jonathan Schlegel、Aliaa Abdelrahman、Christa E. Müller

  DOI：10.1016/j.ejmech.2019.111789

  日期：2020.1

  Dual- or multi-target drugs are particularly promising for the treatment of complex diseases such as (neuro)inflammatory disorders. In the present study, we identified dual antagonists for two related proinflammatory G protein-coupled receptors (GPCRs), the purinergic receptor P2Y(2) receptor, and the orphan receptor GPR17. Based on the lead compound suramin small molecules were designed, synthesized, and modified, including benzenesulfonate, benzenesulfonamide, dibenzamide and diphenylurea derivatives. Structure-activity relationship studies identified 3-nitrophenyl 4-benzamidobenzenesulfonic acid derivatives as dual P2Y(2)R/GPR17 antagonists. In particular, 3-nitrophenyl 4-(4-chlorobenzamido) benzenesulfonate (14l, IC50 3.01 mu M at P2Y(2)R, and 3.37 mu M at GPR17) and 3-nitrophenyl-4-(2-chlorobenzamido)benzenesulfonate (14m, IC50 3.17 mu M at P2Y(2)R, and 1.67 mu M at GPR17) exhibited dual antagonistic activity. Compound 14l was shown to act as an allosteric antagonist at both receptors. In addition, GPR17-selective antagonists were identified( )including 3-nitrophenyl 4-benzamidobenzenesulfonate (14a, IC50 3.20 mu M) and 3-nitrophenyl 4-(3-(trifluoromethyl)benzamido) benzenesulfonate (14f, IC50 3.88 mu M). The developed antagonists were selective versus other closely related P2Y receptors. They were found to possess high chemical and metabolic stability in human liver microsomes and therefore present good starting points for developing potent multi-target drugs with potential applications in inflammatory diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Cremlyn, R. J.; Swinbourne, F. S.; Batchelor, A., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1983, vol. 22, # 10, p. 1029 - 1043
  作者：Cremlyn, R. J.、Swinbourne, F. S.、Batchelor, A.、Honeyman, R.、Nash, D.、et al.

  DOI：——

  日期：——