(R)-N-[(indol-5-yl)methyl]-2-[(3,5-dichloropyridin-2-yl)oxy]butanamide | 1417861-78-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (R)-N-[(indol-5-yl)methyl]-2-[(3,5-dichloropyridin-2-yl)oxy]butanamide
• 英文别名: (2R)-2-(3,5-dichloropyridin-2-yl)oxy-N-(1H-indol-5-ylmethyl)butanamide
• CAS: 1417861-78-9
• 化学式: C₁₈H₁₇Cl₂N₃O₂
• 分子量: 378.258
• InChiKey: SLSYMFIQOLTDDZ-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-methyl 2-((3,5-dichloropyridin-2-yl)oxy)butanoate 在 水 、 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 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (R)-N-[(indol-5-yl)methyl]-2-[(3,5-dichloropyridin-2-yl)oxy]butanamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS)

  摘要：

  The increasing prevalence of drug-resistant bacterial infections is driving the discovery and development not only of new antibiotics, but also of inhibitors of virulence factors that are crucial for in vivo pathogenicity. One such virulence factor is the type III secretion system (T3SS), which plays a critical role in the establishment and dissemination of Pseudomonas aeruginosa infections. We have recently described the discovery and characterization of a series of inhibitors of P. aeruginosa T3SS based on a phenoxyacetamide scaffold. To better characterize the factors involved in potent T3SS inhibition, we have conducted a systematic exploration of this structure, revealing several highly responsive structure-activity relationships indicative of interaction with a specific target. Most of the structural features contributing to potency were additive, and combination of those features produced optimized inhibitors with IC50 values <1 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.011

文献信息

• INHIBITORS OF BACTERIAL TYPE III SECRETION SYSTEM
  申请人：Microbiotix, Inc.

  公开号：EP2731608B1

  公开（公告）日：2018-03-14
• US9340551B2
  申请人：——

  公开号：US9340551B2

  公开（公告）日：2016-05-17
• Synthesis and structure–activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS)
  作者：John D. Williams、Matthew C. Torhan、Venugopal R. Neelagiri、Carson Brown、Nicholas O. Bowlin、Ming Di、Courtney T. McCarthy、Daniel Aiello、Norton P. Peet、Terry L. Bowlin、Donald T. Moir

  DOI：10.1016/j.bmc.2015.01.011

  日期：2015.3

  The increasing prevalence of drug-resistant bacterial infections is driving the discovery and development not only of new antibiotics, but also of inhibitors of virulence factors that are crucial for in vivo pathogenicity. One such virulence factor is the type III secretion system (T3SS), which plays a critical role in the establishment and dissemination of Pseudomonas aeruginosa infections. We have recently described the discovery and characterization of a series of inhibitors of P. aeruginosa T3SS based on a phenoxyacetamide scaffold. To better characterize the factors involved in potent T3SS inhibition, we have conducted a systematic exploration of this structure, revealing several highly responsive structure-activity relationships indicative of interaction with a specific target. Most of the structural features contributing to potency were additive, and combination of those features produced optimized inhibitors with IC50 values <1 mu M. (C) 2015 Elsevier Ltd. All rights reserved.