N-{2-methyl-4-[(methylamino)sulfonyl]phenyl}acetamide | 329946-18-1

• 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-{2-methyl-4-[(methylamino)sulfonyl]phenyl}acetamide
• 英文别名: N-[2-methyl-4-(methylsulfamoyl)phenyl]acetamide
• CAS: 329946-18-1
• 化学式: C₁₀H₁₄N₂O₃S
• mdl: MFCD25962376
• 分子量: 242.299
• InChiKey: JWSUXQAEPNAHJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-{2-methyl-4-[(methylamino)sulfonyl]phenyl}acetamide 在 盐酸 作用下， 以 水 为溶剂， 以98 %的产率得到4-amino-N,3-dimethylbenzenesulfonamide
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶 2 (CDK2) 选择性叔酰胺抑制剂的发现

  摘要：

  细胞周期蛋白依赖性激酶 (CDK) 是细胞周期的关键调节因子，在癌细胞中经常发生改变，从而导致增殖失控。在此背景下，CDK2 已成为抗癌药物开发的一个有吸引力的靶点。在此，我们描述了一系列选择性 CDK2 小分子抑制剂的发现，从我们的 ERK2 计划中的历史化合物（例如化合物6 ）开始。基于结构的药物设计产生了有效且选择性的工具化合物32 ，其中通过分别填充亲脂性 DFG-1 口袋和靶向与 CDK2 特异性下铰链结合残基的相互作用，实现了对 ERK2 和 CDK4 的优异选择性。化合物32在 OVCAR3 肿瘤小鼠中以 50 mg/kg双剂量(BID) 口服给药显示出 112% 的肿瘤生长抑制作用。

  DOI：

  10.1021/acsmedchemlett.3c00142
• 作为产物：
  描述：

  sodium 4-(acetylamino)-3-methylbenzenesulfonate 在 氯化亚砜 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 N-{2-methyl-4-[(methylamino)sulfonyl]phenyl}acetamide
  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

文献信息

• Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor
  作者：Karen R. Romines、George A. Freeman、Lee T. Schaller、Jill R. Cowan、Steve S. Gonzales、Jeffrey H. Tidwell、Clarence W. Andrews、David K. Stammers、Richard J. Hazen、Robert G. Ferris、Steven A. Short、Joseph H. Chan、Lawrence R. Boone

  DOI：10.1021/jm050670l

  日期：2006.1.1

  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.
• Discovery of Selective Tertiary Amide Inhibitors of Cyclin-Dependent Kinase 2 (CDK2)
  作者：Mingshuo Zeng、Jessica M. Grandner、Marian C. Bryan、Vishal Verma、Robin Larouche-Gauthier、Jean-Philippe Leclerc、Liang Zhao、Pouyan Haghshenas、Samuel Aubert-Nicol、Arun Yadav、Melissa Ashley、Jacob Z. Chen、Matthew Durk、Karen E. Samy、Marika Nespi、Elizabeth Levy、Karl Merrick、John G. Moffat、Jeremy Murray、Angela Oh、Christine Orr、Ehud Segal、Jessica Sims、Christopher Sneeringer、Madeleine Prangley、Steffan Vartanian、Steven Magnuson、Brendan T. Parr

  DOI：10.1021/acsmedchemlett.3c00142

  日期：2023.9.14

  Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and are frequently altered in cancer cells, thereby leading to uncontrolled proliferation. In this context, CDK2 has emerged as an appealing target for anticancer drug development. Herein, we describe the discovery of a series of selective small molecule inhibitors of CDK2 beginning with historical compounds from our ERK2 program

  细胞周期蛋白依赖性激酶 (CDK) 是细胞周期的关键调节因子，在癌细胞中经常发生改变，从而导致增殖失控。在此背景下，CDK2 已成为抗癌药物开发的一个有吸引力的靶点。在此，我们描述了一系列选择性 CDK2 小分子抑制剂的发现，从我们的 ERK2 计划中的历史化合物（例如化合物6 ）开始。基于结构的药物设计产生了有效且选择性的工具化合物32 ，其中通过分别填充亲脂性 DFG-1 口袋和靶向与 CDK2 特异性下铰链结合残基的相互作用，实现了对 ERK2 和 CDK4 的优异选择性。化合物32在 OVCAR3 肿瘤小鼠中以 50 mg/kg双剂量(BID) 口服给药显示出 112% 的肿瘤生长抑制作用。