1-(4-(4-(1-acetyl-2-methylindolin-5-ylsulfonyl)piperazin-1-yl)phenyl)ethanone | 901037-01-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(4-(1-acetyl-2-methylindolin-5-ylsulfonyl)piperazin-1-yl)phenyl)ethanone
• 英文别名: 1-[4-[4-(1-Acetyl-2-methyl-indolin-5-yl)sulfonylpiperazino]phenyl]ethanone；1-[4-[4-[(1-acetyl-2-methyl-2,3-dihydroindol-5-yl)sulfonyl]piperazin-1-yl]phenyl]ethanone
• CAS: 901037-01-2
• 化学式: C₂₃H₂₇N₃O₄S
• 分子量: 441.551
• InChiKey: KKTXEJHXGWOSSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  86.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲基吲哚啉 在 吡啶 、 氯磺酸 、 五氯化磷 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-(4-(1-acetyl-2-methylindolin-5-ylsulfonyl)piperazin-1-yl)phenyl)ethanone
  参考文献：
  名称：

  Identification of Inhibitors of NOD1-Induced Nuclear Factor-κB Activation

  摘要：

  NOD1 (nucleotide-binding oligomerization domain 1) protein is a member of the NLR (NACHT and leucine rich repeat domain containing proteins) protein family, which plays a key role in innate immunity as a sensor of specific microbial components derived from bacterial peptidoglycans and induction of inflammatory responses. Mutations in NOD proteins have been associated with various inflammatory diseases that affect NF-kappa B (nuclear factor kappa B) activity, a major signaling pathway involved in apoptosis, inflammation, and immune response. A luciferase-based reporter gene assay was utilized in a high-throughput screening program conducted under the NIH-sponsored Molecular Libraries Probe Production Center Network program to identify the active scaffolds. Herein, we report the chemical synthesis, structure-activity relationship studies, downstream counterscreens, secondary assay data, and pharmacological profiling of the 2-aminobenzimidazole lead (compound 1c, ML130) as a potent and selective inhibitor of NOD 1-induced NF-kappa B activation.

  DOI：

  10.1021/ml200158b

文献信息

• Discovery of a Novel Noniminosugar Acid α Glucosidase Chaperone Series
  作者：Jingbo Xiao、Wendy Westbroek、Omid Motabar、Wendy A. Lea、Xin Hu、Arash Velayati、Wei Zheng、Noel Southall、Ann Marie Gustafson、Ehud Goldin、Ellen Sidransky、Ke Liu、Anton Simeonov、Rafael J. Tamargo、Antonia Ribes、Leslie Matalonga、Marc Ferrer、Juan J. Marugan

  DOI：10.1021/jm3005543

  日期：2012.9.13

  Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the lysosomal enzyme acid a-glucosidase (GAA). Many disease-causing mutated GAA retain enzymatic activity but are not translocated from endoplasmic reticulum (ER) to lysosomes. Enzyme replacement therapy (ERT) is the only treatment for Pompe disease but remains expensive, inconvenient, and does not reverse all disease manifestations. It was postulated that small molecules which aid in protein folding and translocation to lysosomes could provide an alternate to ERT. Previously, several iminosugars have been proposed as small-molecule chaperones for specific LSDs. Here we identified a novel series of noniminosugar chaperones for GAA. These moderate GAA inhibitors are shown to bind and thermostabilize GAA and increase GAA translocation to lysosomes in both wild-type and Pompe fibroblasts. AMDE and physical properties studies indicate that this series is a promising lead for further pharmacokinetic evaluation and testing in Pompe disease models.
• Identification of Inhibitors of NOD1-Induced Nuclear Factor-κB Activation
  作者：Pasha M. Khan、Ricardo G. Correa、Daniela B. Divlianska、Satyamaheshwar Peddibhotla、E. Hampton Sessions、Gavin Magnuson、Brock Brown、Eigo Suyama、Hongbin Yuan、Arianna Mangravita-Novo、Michael Vicchiarelli、Ying Su、Stefan Vasile、Layton H. Smith、Paul W. Diaz、John C. Reed、Gregory P. Roth

  DOI：10.1021/ml200158b

  日期：2011.10.13

  NOD1 (nucleotide-binding oligomerization domain 1) protein is a member of the NLR (NACHT and leucine rich repeat domain containing proteins) protein family, which plays a key role in innate immunity as a sensor of specific microbial components derived from bacterial peptidoglycans and induction of inflammatory responses. Mutations in NOD proteins have been associated with various inflammatory diseases that affect NF-kappa B (nuclear factor kappa B) activity, a major signaling pathway involved in apoptosis, inflammation, and immune response. A luciferase-based reporter gene assay was utilized in a high-throughput screening program conducted under the NIH-sponsored Molecular Libraries Probe Production Center Network program to identify the active scaffolds. Herein, we report the chemical synthesis, structure-activity relationship studies, downstream counterscreens, secondary assay data, and pharmacological profiling of the 2-aminobenzimidazole lead (compound 1c, ML130) as a potent and selective inhibitor of NOD 1-induced NF-kappa B activation.