N-[4-(aminosulfonyl)-2-methylphenyl]-2-(4-chloro-2-aminophenoxy)acetamide | 1341199-24-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[4-(aminosulfonyl)-2-methylphenyl]-2-(4-chloro-2-aminophenoxy)acetamide
• 英文别名: 2-(2-amino-4-chlorophenoxy)-N-(2-methyl-4-sulfamoylphenyl)acetamide
• CAS: 1341199-24-3
• 化学式: C₁₅H₁₆ClN₃O₄S
• 分子量: 369.829
• InChiKey: LWCUEYNCWUCHHM-UHFFFAOYSA-N

物化性质

• 熔点：
  251.1-252.9 °C
• 密度：
  1.477±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[4-(aminosulfonyl)-2-methylphenyl]-2-(4-chloro-2-aminophenoxy)acetamide 、 3-(三氟甲基)苯甲酰氯 在 碳酸氢钠 作用下， 以 丙酮 为溶剂， 反应 0.67h， 以72%的产率得到N-[5-chloro-2-[2-(2-methyl-4-sulfamoyl-anilino)-2-oxo-ethoxy]phenyl]-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Synthesis, structure–activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors

  摘要：

  A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC50 values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC50 = 0.30 nM, TI = 184 578), 131 (EC50 = 0.37 nM, TI = 212 819), 13m (EC50 = 0.32 nM, TI = 260 617) and 13r (EC50 = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC50 values of 0.29 mu M, 0.14 mu M, 0.10 mu M and 0.27 mu M, respectively. In particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 mu M concentration. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.032
• 作为产物：
  描述：

  4-氯-2-硝基苯酚 在 氯化亚砜 、 四丁基溴化铵 、 铁粉 、 碳酸氢钠 、 potassium carbonate 、 氯化铵 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 18.0h， 生成 N-[4-(aminosulfonyl)-2-methylphenyl]-2-(4-chloro-2-aminophenoxy)acetamide
  参考文献：
  名称：

  Synthesis, structure–activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors

  摘要：

  A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC50 values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC50 = 0.30 nM, TI = 184 578), 131 (EC50 = 0.37 nM, TI = 212 819), 13m (EC50 = 0.32 nM, TI = 260 617) and 13r (EC50 = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC50 values of 0.29 mu M, 0.14 mu M, 0.10 mu M and 0.27 mu M, respectively. In particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 mu M concentration. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.032

文献信息

• Identification of the novel N-phenylbenzenesulfonamide derivatives as potent HIV inhibitors
  作者：Yong Sun、Cui-Lin Lu、Chang-Yuan Wang、Rui-Rui Wang、Ke-Xin Liu、Liu-Meng Yang、Yu-Hong Zhen、Hou-Li Zhang、Chao Wang、Yong-Tang Zheng、Xiao-Dong Ma

  DOI：10.1016/j.cclet.2014.11.004

  日期：2015.2

  Searching for more safe and effective agents for HIV treatments is still an urgent topic worldwide. Based on our continuous modifications on the benzophenone derivatives as HIV-1 reverse transcriptase (RT) inhibitors, a new template bearing N-phenylbenzenesulfonamide (PBSA) structure was designed to enhance the interactions with HIV-1 RT. In this manuscript, a series of PBSA derivatives were synthesized and evaluated for their anti-HIV-1 activity. The preliminary test showed that these compounds were potent to inhibit wild-type HIV-1 with EC50 values ranging of 0.105-14.531 mu mol/L. In particular, compound 13f not only has high anti-HIV-1 activity (0.108 mu mol/L), but also possesses low toxicity with a TI value of 1816.6. Furthermore, the major interactions of the inhibitor 13f with HIV-1 RT were also investigated using the molecular modelling. Our discovered structure-activity relationships (SARs) of these analogues may serve as an important clue for further optimizations. (C) 2014 Yong-Tang Zheng and Xiao-Dong Ma. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.
• Synthesis, structure–activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors
  作者：Xiao-Dong Ma、Qiu-Qin He、Xuan Zhang、Shi-Qiong Yang、Liu-Meng Yang、Shuang-Xi Gu、Yong-Tang Zheng、Fen-Er Chen、Hui-Fang Dai

  DOI：10.1016/j.ejmech.2012.03.032

  日期：2012.12

  A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC50 values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC50 = 0.30 nM, TI = 184 578), 131 (EC50 = 0.37 nM, TI = 212 819), 13m (EC50 = 0.32 nM, TI = 260 617) and 13r (EC50 = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC50 values of 0.29 mu M, 0.14 mu M, 0.10 mu M and 0.27 mu M, respectively. In particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 mu M concentration. (C) 2012 Elsevier Masson SAS. All rights reserved.