5-(morpholinosulfonyl)-2-(pyrrolidin-1-yl)aniline | 328106-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 5-(morpholinosulfonyl)-2-(pyrrolidin-1-yl)aniline
• 英文别名: 5-(Morpholine-4-sulfonyl)-2-pyrrolidin-1-yl-phenylamine；5-morpholin-4-ylsulfonyl-2-pyrrolidin-1-ylaniline
• CAS: 328106-72-5
• 化学式: C₁₄H₂₁N₃O₃S
• mdl: MFCD02720435
• 分子量: 311.405
• InChiKey: AVXOENYLRRSKPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-甲基噻唑-2-甲酸 、 5-(morpholinosulfonyl)-2-(pyrrolidin-1-yl)aniline 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以13%的产率得到5-methyl-N-(5-(morpholinosulfonyl)-2-(pyrrolidin-1-yl)phenyl)thiazole-2-carboxamide
  参考文献：
  名称：

  Editing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors

  摘要：

  The oligosaccharyltransferase (OST) is a multisubunit enzyme complex that N-glycosylates proteins in the secretory pathway and is considered to be constitutive and unregulated. However, small-molecule OST inhibitors such as NGI-1 provide a pharmacological approach for regulating N-I inked glycosylation. Herein we design cell models with knockout of each OST catalytic subunit (STT3A or STT3B) to screen the activity of NGI-1 and its analogs. We show that NGI-1 targets the function of both STT3A and STT3B and use structure-activity relationships to guide synthesis of catalytic subunit-specific inhibitors. Using this approach, pharmacophores that increase STT3B selectivity are characterized and an STT3B-specific inhibitor is identified. This inhibitor has discrete biological effects on endogenous STT3B target proteins such as COX2 but does not activate the cellular unfolded protein response. Together this work demonstrates that subsets of glycoproteins can be regulated through pharmacologic inhibition of N-linked glycosylation.

  DOI：

  10.1016/j.chembiol.2018.07.005
• 作为产物：
  描述：

  4-氟-3-硝基苯磺酰氯 在 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 5-(morpholinosulfonyl)-2-(pyrrolidin-1-yl)aniline
  参考文献：
  名称：

  Editing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors

  摘要：

  The oligosaccharyltransferase (OST) is a multisubunit enzyme complex that N-glycosylates proteins in the secretory pathway and is considered to be constitutive and unregulated. However, small-molecule OST inhibitors such as NGI-1 provide a pharmacological approach for regulating N-I inked glycosylation. Herein we design cell models with knockout of each OST catalytic subunit (STT3A or STT3B) to screen the activity of NGI-1 and its analogs. We show that NGI-1 targets the function of both STT3A and STT3B and use structure-activity relationships to guide synthesis of catalytic subunit-specific inhibitors. Using this approach, pharmacophores that increase STT3B selectivity are characterized and an STT3B-specific inhibitor is identified. This inhibitor has discrete biological effects on endogenous STT3B target proteins such as COX2 but does not activate the cellular unfolded protein response. Together this work demonstrates that subsets of glycoproteins can be regulated through pharmacologic inhibition of N-linked glycosylation.

  DOI：

  10.1016/j.chembiol.2018.07.005

文献信息

• Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1
  作者：Yalda Bravo、Peter Teriete、Raveendra-Panickar Dhanya、Russell Dahl、Pooi San Lee、Tina Kiffer-Moreira、Santhi Reddy Ganji、Eduard Sergienko、Layton H. Smith、Colin Farquharson、José Luis Millán、Nicholas D.P. Cosford

  DOI：10.1016/j.bmcl.2014.07.013

  日期：2014.9

  We report the discovery and characterization of a series of benzoisothiazolone inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in skeletal mineralization and soft tissue ossification abnormalities. High-throughput screening (HTS) of a small molecule library led to the identification of benzoisothiazolones as potent and selective inhibitors of PHOSPHO1. Critical structural requirements for activity were determined, and the compounds were subsequently derivatized and measured for in vitro activity and ADME parameters including metabolic stability and permeability. On the basis of its overall profile the benzoisothiazolone analogue 2q was selected as MLPCN probe ML086.
• ——
  作者：V. A. Chornous、N. V. Mel'nichenko、M. K. Bratenko、M. V. Vovk

  DOI：10.1023/a:1016394311649

  日期：——

  3-Aryl(heteryl)-1-phenyl-4-pyrazolecarbonyl isothiocyanates were synthesized by treatment of 3-aryl(heteryl)-1-phenyl-4-pyrazolecarbonyl chlorides with lead, sodium, or ammonium thiocyanate. Their reactions with amines, hydrazines, and acylhydrazines gave the corresponding thioureas and thiosemicarbazides.
• One-Pot Synthesis of 2,3-Dihydro-1<i>H</i>-benzimidazoles
  作者：Sergey V. Ryabukhin、Andrey S. Plaskon、Dmitry M. Volochnyuk、Alexander N. Shivanyuk、Andrey A. Tolmachev

  DOI：10.1021/jo0712087

  日期：2007.9.1

  [GRAPHICS]A convenient one-pot method for the synthesis of 2,3dihydro-IH-benzimidazoles has been elaborated. A set of 2,3-dihydro-IH-benzimidazoles was prepared from various ortho-dialkylaminoanilines and aldehydes using Me3SiCl as a condensation agent and pyridine as a basic medium.