N-(4-(morpholinosulfonyl)phenyl)-4-nitrobenzamide

• 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-(morpholinosulfonyl)phenyl)-4-nitrobenzamide
• 英文别名: SID 117695369；N-[4-(morpholin-4-ylsulfonyl)phenyl]-4-nitrobenzamide；N-(4-morpholin-4-ylsulfonylphenyl)-4-nitrobenzamide
• 化学式: C₁₇H₁₇N₃O₆S
• 分子量: 391.404
• InChiKey: AKRBIRGHWGUQDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(吗啉磺酰)苯胺 、 4-硝基苯甲酰氯 以 乙腈 为溶剂， 反应 0.33h， 以38%的产率得到N-(4-(morpholinosulfonyl)phenyl)-4-nitrobenzamide
  参考文献：
  名称：

  Discovery of Sulfonamidebenzamides as Selective Apoptotic CHOP Pathway Activators of the Unfolded Protein Response

  摘要：

  Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathway facilitates the clearance of the undesired proteins; however, if overwhelmed, cells trigger apoptosis by upregulating transcription factors such as C/EBP-homologous protein (CHOP). A high throughput screen was performed directed at identifying compounds that selectively upregulate the apoptotic CHOP pathway while avoiding adaptive signaling cascades, resulting in a sulfonamidebenzamide chemotype that was optimized. These efforts produced a potent and selective CHOP inducer (AC(50) = 0.8 mu M; XBP1 > 80 mu M), which was efficacious in both mouse embryonic fibroblast cells and a human oral squamous cell cancer cell line, and demonstrated antiproliferative effects for multiple cancer cell lines in the NCI-60 panel.

  DOI：

  10.1021/ml5003234

文献信息

• COMPOUNDS AND METHODS FOR ACTIVATING THE APOPTOTIC ARM OF THE UNFOLDED PROTEIN RESPONSE
  申请人：University of Kansas

  公开号：US20150203477A1

  公开（公告）日：2015-07-23

  N-substituted sulfonylphenyl-5-nitrofuranyl-2-carboxamide derived compounds, which selectively activate the apoptotic, but not the adaptive arm, of the Unfolded Protein Response are provides as is their use in the treatment of diseases such as diabetes, Alzheimer's, Parkinson's, hemophilia, lysosomal storage diseases and cancer.

  提供了N-取代磺酰基苯基-5-硝基呋喃-2-羧酰胺衍生物化合物，其选择性激活蛋白质错配反应的凋亡分支而非适应性分支，并且可以用于治疗糖尿病、阿尔茨海默病、帕金森病、血友病、溶酶体贮积病和癌症。
• Compounds and methods for activating the apoptotic arm of the unfolded protein response
  申请人：University of Kansas

  公开号：US10787439B2

  公开（公告）日：2020-09-29

  N-substituted sulfonylphenyl-5-nitrofuranyl-2-carboxamide derived compounds, which selectively activate the apoptotic, but not the adaptive arm, of the Unfolded Protein Response are provides as is their use in the treatment of diseases such as diabetes, Alzheimer's, Parkinson's, hemophilia, lysosomal storage diseases and cancer.

  提供了 N-取代磺酰基苯基-5-硝基呋喃基-2-甲酰胺衍生化合物，这些化合物可选择性地激活折叠蛋白反应的凋亡臂而非适应臂，并可用于治疗糖尿病、阿尔茨海默氏症、帕金森氏症、血友病、溶酶体贮积症和癌症等疾病。
• US9732067B2
  申请人：——

  公开号：US9732067B2

  公开（公告）日：2017-08-15
• Discovery of Sulfonamidebenzamides as Selective Apoptotic CHOP Pathway Activators of the Unfolded Protein Response
  作者：Daniel P. Flaherty、Justin R. Miller、Danielle M. Garshott、Michael Hedrick、Palak Gosalia、Yujie Li、Monika Milewski、Eliot Sugarman、Stefan Vasile、Sumeet Salaniwal、Ying Su、Layton H. Smith、Thomas D. Y. Chung、Anthony B. Pinkerton、Jeffrey Aubé、Michael U. Callaghan、Jennifer E. Golden、Andrew M. Fribley、Randal J. Kaufman

  DOI：10.1021/ml5003234

  日期：2014.12.11

  Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathway facilitates the clearance of the undesired proteins; however, if overwhelmed, cells trigger apoptosis by upregulating transcription factors such as C/EBP-homologous protein (CHOP). A high throughput screen was performed directed at identifying compounds that selectively upregulate the apoptotic CHOP pathway while avoiding adaptive signaling cascades, resulting in a sulfonamidebenzamide chemotype that was optimized. These efforts produced a potent and selective CHOP inducer (AC(50) = 0.8 mu M; XBP1 > 80 mu M), which was efficacious in both mouse embryonic fibroblast cells and a human oral squamous cell cancer cell line, and demonstrated antiproliferative effects for multiple cancer cell lines in the NCI-60 panel.