4-氨基-N-(2,4-二氟苯基)苯磺酰胺 | 1717-36-8

• 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-氨基-N-(2,4-二氟苯基)苯磺酰胺
• 英文名称: 4-amino(N-(2,4-difluorophenyl)benzenesulfonamide)
• 英文别名: 4-amino-N-(2,4-difluorophenyl)benzenesulfonamide
• CAS: 1717-36-8
• 化学式: C₁₂H₁₀F₂N₂O₂S
• mdl: MFCD01935782
• 分子量: 284.286
• InChiKey: LYWJIXGZACXKRN-UHFFFAOYSA-N

物化性质

• 沸点：
  425.6±55.0 °C(Predicted)
• 密度：
  1.502±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 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：
  80.6
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  2,3-二氯-1,4-萘醌 、 4-氨基-N-(2,4-二氟苯基)苯磺酰胺 以 乙醇 为溶剂， 反应 72.0h， 以62%的产率得到4-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino)-N-(2,4-difluorophenyl)benzenesulfonamide
  参考文献：
  名称：

  Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors

  摘要：

  Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the beta 5 and beta 6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the beta 6 subunit. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.038

文献信息

• Design, synthesis and SAR of new-di-substituted pyridopyrimidines as ATP-competitive dual PI3Kα/mTOR inhibitors
  作者：Aisha A.K. Al-Ashmawy、Fatma A. Ragab、Khaled M. Elokely、Manal M. Anwar、Oscar Perez-Leal、Mario C. Rico、John Gordon、Eugeney Bichenkov、George Mateo、Emad M.M. Kassem、Gehan H. Hegazy、Magid Abou-Gharbia、Wayne Childers

  DOI：10.1016/j.bmcl.2017.05.044

  日期：2017.7

  PI3Kα/mTOR ATP-competitive inhibitors are considered as one of the promising molecularly targeted cancer therapeutics. Based on lead compound A from the literature, two similar series of 2-substituted-4-morpholino-pyrido[3,2-d]pyrimidine and pyrido[2,3-d]pyrimidine analogs were designed and synthesized as PI3Kα/mTOR dual inhibitors. Interestingly, most of the series gave excellent inhibition for both

  PI3Kα/ mTOR ATP竞争性抑制剂被认为是有前途的分子靶向癌症治疗剂之一。基于文献中的铅化合物A，设计并合成了两个相似的2-取代-4-吗啉代-吡啶并[3,2- d ]嘧啶和吡啶并[2,3- d ]嘧啶类似物系列，并将其合成为PI3Kα/ mTOR dual抑制剂。有趣的是，大多数系列均对两种酶均具有优异的抑制作用，IC 50值范围从一位到两位数nM。与许多PI3Kα/ mTOR双重抑制剂不同，我们的化合物显示出对PI3Kα的选择性。基于其强大的酶抑制活性，对PI3Kα的选择性以及在2D细胞培养活力测定中良好的治疗指数，化合物4h选择在3D培养中评估其针对MCF7乳腺癌细胞的IC 50以及与这两种酶的对接研究。
• Discovery and SAR of Novel Disubstituted Quinazolines as Dual PI3Kalpha/mTOR Inhibitors Targeting Breast Cancer
  作者：Aisha A. K. Al-Ashmawy、Khaled M. Elokely、Oscar Perez-Leal、Mario Rico、John Gordon、George Mateo、Abdelsattar M. Omar、Magid Abou-Gharbia、Wayne E. Childers

  DOI：10.1021/acsmedchemlett.0c00289

  日期：2020.11.12

  The dual PI3Kα/ m TOR inhibitors represent a promising molecularly targeted therapy for cancer. Here, we documented the discovery of new 2,4-disubstituted quinazoline analogs as potent dual PI3Kα/sm TOR inhibitors. Our structure based chemistry endeavor yielded six excellent compounds 9e, 9f, 9g, 9k, 9m, and 9o with single/double digit nanomolar IC50 values against both enzymes and acceptable aqueous

  双 PI3Kα/m TOR 抑制剂代表了一种有前途的癌症分子靶向治疗。在这里，我们记录了新的 2,4-二取代喹唑啉类似物作为有效的双重 PI3Kα/sm TOR 抑制剂的发现。我们基于结构的化学努力产生了六种优异的化合物9e、9f、9g、9k、9m和9o，其对两种酶的IC 50值为单位/两位数，并且具有可接受的水溶性和氧化代谢稳定性。其中一种类似物9m具有磺酰胺取代基，以前没有描述过这种化学支架。短直接合成路线，构效关系，体外描述了针对正常成纤维细胞和 3 个乳腺癌细胞系的 2D 细胞培养活力测定，以及针对该系列的 MCF7 细胞的体外3D 培养活力测定。
• Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors
  作者：Harshani R. Lawrence、Aslamuzzaman Kazi、Yunting Luo、Robert Kendig、Yiyu Ge、Sanjula Jain、Kenyon Daniel、Daniel Santiago、Wayne C. Guida、Saïd M. Sebti

  DOI：10.1016/j.bmc.2010.06.038

  日期：2010.8

  Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the beta 5 and beta 6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the beta 6 subunit. (C) 2010 Elsevier Ltd. All rights reserved.