N-[4-(aminosulfonyl)-2-methylphenyl]-2-bromoacetamide | 329944-57-2

• 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-bromoacetamide
• 英文别名: 2-bromo-N-(2-methyl-4-sulfamoylphenyl)acetamide
• CAS: 329944-57-2
• 化学式: C₉H₁₁BrN₂O₃S
• 分子量: 307.168
• InChiKey: CKKXQNICHOCCBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[4-(aminosulfonyl)-2-methylphenyl]-2-bromoacetamide 在 2-chloro-N-(2-methyl-4-sulfamoyl-phenyl)-acetamide 、 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 20.0h， 以92%的产率得到N-[4-(aminosulfonyl)-2-methylphenyl]-2-iodoacetamide
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor

  摘要：

  Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.

  DOI：

  10.1021/jm050670l
• 作为产物：
  描述：

  3-甲基-4-氨基苯磺酰胺 、 溴乙酰溴 在 吡啶 作用下， 以 氯仿 为溶剂， 以69%的产率得到N-[4-(aminosulfonyl)-2-methylphenyl]-2-bromoacetamide
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor

  摘要：

  Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.

  DOI：

  10.1021/jm050670l
• 作为试剂：
  描述：

  N-[4-(aminosulfonyl)-2-methylphenyl]-2-bromoacetamide 、 3-chloro-5-(5-chloro-2-hydroxybenzoyl)benzonitrile 在 N-[4-(aminosulfonyl)-2-methylphenyl]-2-bromoacetamide 作用下， 以12的产率得到N-[4-(aminosulfonyl)-2-methylphenyl]-2-[4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetamide
  参考文献：
  名称：

  J. Med. Chem. 2006, 49, 727-739

  摘要：

  DOI：

文献信息

• Visible light-driven direct synthesis of ketones from aldehydes via C H bond activation using NiCu nanoparticles adorned on carbon nano onions
  作者：Zahra Khorsandi、S. Fatemeh Mohammadi Metkazini、Akbar Heydari、Rajender S. Varma

  DOI：10.1016/j.mcat.2021.111987

  日期：2021.11

  An efficient, straightforward and high yield synthetic approach is described for the direct synthesis of diaryl ketones via the CH bond activation of aldehydes using NiCu nanoparticles adorned on carbon nano onions as an efficient heterogeneous catalyst under the irradiation of a mercury-vapor lamp (400 w) via simple workup. This CH bond activation reaction appears simple and convenient with a wide

  描述了一种高效、直接和高收率的合成方法，用于通过醛的 CH键活化直接合成二芳基酮，使用装饰在碳纳米洋葱上的 NiCu 纳米粒子作为高效的多相催化剂，在汞蒸气灯 (400 w) 通过简单的检查。这种C H键活化反应因其优异的合成能力而显得简单方便，底物范围广，如在更绿色温和的反应条件下制备新批准的抗阿尔茨海默病和抗HIV药物化合物所示；催化剂可以循环使用5次，催化活性没有任何损失。
• Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Xiao-Dong Ma、Xuan Zhang、Hui-Fang Dai、Shi-Qiong Yang、Liu-Meng Yang、Shuang-Xi Gu、Yong-Tang Zheng、Qiu-Qin He、Fen-Er Chen

  DOI：10.1016/j.bmc.2011.06.007

  日期：2011.8

  A novel series of benzophenone derivatives with B-ring substituted by naphthyl ring has been synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Most of these compounds showed good to moderate activity against wild-type HIV-1 and mutated viruses. In particular, the analogue 10i demonstrated the most potent activity against wild-type HIV-1 with an EC50 value of 4.8 nM

  合成了一系列新的苯环被萘环取代的二苯甲酮衍生物，并将其作为非核苷HIV-1逆转录酶抑制剂进行了评估。这些化合物中的大多数对野生型HIV-1和突变病毒显示出良好至中等的活性。特别是，类似物10i对野生型HIV-1表现出最强的活性，EC 50值为4.8 nM，并且具有高达10347.9的高选择性指数，还被证明对HIV-1双重突变体具有活性。带有EC 50的菌株A 17（K103N + Y181C）值为2.1μM。此外，分子模型研究被用于探索有效抑制剂与HIV-1 RT之间的主要相互作用。结构-活性关系的研究可能是进一步优化的重要线索。
• Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Xiao-Dong Ma、Xuan Zhang、Shi-Qiong Yang、Hui-Fang Dai、Liu-Meng Yang、Shuang-Xi Gu、Yong-Tang Zheng、Qiu-Qin He、Fen-Er Chen

  DOI：10.1016/j.bmc.2011.07.003

  日期：2011.8

  A series of (±)-benzhydrol derivatives featuring the essential sulfonamide group at the para position on the C-ring were synthesized and evaluated for the potential anti-HIV activity in C8166 cells. Most of these analogues demonstrated low concentration inhibitory activity with EC50 values less than 1 μM against the wild-type HIV-1. In particular, compound 7h was identified as the highest active inhibitor

  合成了一系列在（C）环对位上具有必需磺酰胺基的（±）-苯氢衍生物，并评估了C8166细胞中潜在的抗HIV活性。这些类似物中的大多数都表现出低浓度的抑制活性，对野生型HIV-1的EC 50值小于1μM。尤其是，化合物7h被确定为野生型HIV-1的最高活性抑制剂，EC 50值为0.12μM，选择性指数值为312.73。此外，它们中的一些还对带有EC 50的双重突变菌株A 17（K103N + Y181C）表现出中等活性。值低于5μM。此外，还探索了与RT的结合模式以及这些衍生物的初步结构-活性关系，以进行进一步的化学修饰。
• Benzophenones as inhibitors of reverse transcriptase
  申请人：SmithKline Beecham Corporation

  公开号：US06995283B2

  公开（公告）日：2006-02-07

  The present invention is directed to beazophenone compounds useful in the inhibition of HIV reverse transcriptase, particularly its resistant varieties.

  本发明涉及苯并酮化合物，其在抑制HIV逆转录酶方面具有用处，特别是在抑制其耐药品种方面。
• BENZOPHENONES AS INHIBITORS OF REVERSE TRANSCRIPTASE
  申请人：GLAXO GROUP LIMITED

  公开号：EP1208091B1

  公开（公告）日：2006-05-03