N-((5-bromo-2-methyl-1(phenylsulfonyl)-1H-indol-3-yl)methyl)hydroxylamine | 919295-70-8

• 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-((5-bromo-2-methyl-1(phenylsulfonyl)-1H-indol-3-yl)methyl)hydroxylamine
• 英文别名: N-[[1-(benzenesulfonyl)-5-bromo-2-methylindol-3-yl]methyl]hydroxylamine
• CAS: 919295-70-8
• 化学式: C₁₆H₁₅BrN₂O₃S
• 分子量: 395.277
• InChiKey: COOAHIHXYGMJJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  79.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-((5-bromo-2-methyl-1(phenylsulfonyl)-1H-indol-3-yl)methyl)hydroxylamine 、 甲酸 在 乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以50 mg的产率得到N-(1-benzenesulfonyl-5-bromo-2-methyl-1H-indol-3-ylmethyl)N-hydroxyformamide
  参考文献：
  名称：

  Discovery and Refinement of a New Structural Class of Potent Peptide Deformylase Inhibitors

  摘要：

  New classes of antibiotics are urgently needed to counter increasing levels of pathogen resistance. Peptide deformylase (PDF) was originally selected as a specific bacterial target, but a human homologue, the inhibition of which causes cell death, was recently discovered. We developed a dual-screening strategy for selecting highly effective compounds with low inhibition effect against human PDF. We selected a new scaffold in vitro that discriminated between human and bacterial PDFs. Analyses of structure-activity relationships identified potent antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the same mode of action in vivo as previously identified PDF inhibitors but without the apoptotic effects of these inhibitors in human cells.

  DOI：

  10.1021/jm060910c
• 作为产物：
  描述：

  5-溴-2-甲基吲哚-3-羧醛 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.25h， 生成 N-((5-bromo-2-methyl-1(phenylsulfonyl)-1H-indol-3-yl)methyl)hydroxylamine
  参考文献：
  名称：

  Discovery and Refinement of a New Structural Class of Potent Peptide Deformylase Inhibitors

  摘要：

  New classes of antibiotics are urgently needed to counter increasing levels of pathogen resistance. Peptide deformylase (PDF) was originally selected as a specific bacterial target, but a human homologue, the inhibition of which causes cell death, was recently discovered. We developed a dual-screening strategy for selecting highly effective compounds with low inhibition effect against human PDF. We selected a new scaffold in vitro that discriminated between human and bacterial PDFs. Analyses of structure-activity relationships identified potent antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the same mode of action in vivo as previously identified PDF inhibitors but without the apoptotic effects of these inhibitors in human cells.

  DOI：

  10.1021/jm060910c

文献信息

• PEPTIDE DEFORMYLASE INHIBITORS, THEIR USE, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
  申请人：Centre National de la Recherche Scientifique

  公开号：EP1838302A2

  公开（公告）日：2007-10-03
• [EN] PEPTIDE DEFORMYLASE INHIBITORS, THEIR USE, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME<br/>[FR] INHIBITEURS DE PEPTIDE DEFORMYLASE, UTILISATIONS DE CEUX-CI ET COMPOSITIONS PHARMACEUTIQUES CONTENANT CES INHIBITEURS
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2006077139A2

  公开（公告）日：2006-07-27

  [EN] The present invention relates to the use of compounds having: a) the following general formula (I): wherein: independently from each other, R₂ and R₃ represent H, an alkyl group from 1 to 5 carbon atoms, or a metal chelating group from 2 to 20 atoms comprising from 1 to 5 heteroatoms; independently from one another, R₄, R₅, R₆, and R₇ represent H, a halogen, or a group comprising from 1 to 10 carbon atoms; R₁ represents H, or a group comprising from 1 to 50 carbon atoms; provided that at least one of R₂ and R₃ represents a metal chelating group as defined above ; and b) an IC50 lower than about 1 µM with respect to the Escherichia coli nickelbound peptide deformylase (SEQ ID NO: 1) and/or to the Bacillus stearothermophilus nickelbound peptide deformylase (SEQ ID NO: 2), or of pharmaceutically acceptable salts thereof, for the manufacture of medicaments intended for the prevention or the treatment of bacterial infections or protozoan infections, or for the manufacture of herbicides.
  [FR] La présente invention concerne l'utilisation de composés représentés (a) par la formule générale suivante (I). Dans cette formule, R₂ et R₃ sont indépendants entre eux et représentent H, un groupe alkyle de un à cinq atomes de carbone ou un groupe de chélation métallique de 2 à 20 atomes comprenant de un à cinq hétéroatomes, indépendamment l'un de l'autre, R₄, R₅, R₆, and R₇ représentent H, un groupe allogène ou un groupe comprenant de un à dix atomes de carbone, R₁ représente H, ou un groupe comprenant de un à 50 atomes de carbone, sous réserve qu'au moins un des R₂ et R₃ représente un groupe de chélation métallique tel que défini ci-dessus et, (b) un IC50 inférieur à environ 1 ?M par rapport à la peptide déformylase à liaison nickel à Escherichia coli (SEQ ID NO: 1) et/ou à la peptide déformylase à liaison nickel à Bacillus stearothermophilus (SEQ ID NO: 2), ou des sels de ceux-ci répondant aux normes pharmaceutiques fabrication de médicaments destinés à la prévention ou retraitement d'infections bactériennes ou d'infections par protozoaires ou à fabrication d'herbicides.
• Discovery and Refinement of a New Structural Class of Potent Peptide Deformylase Inhibitors
  作者：Adrien Boularot、Carmela Giglione、Sylvain Petit、Yann Duroc、Rodolphe Alves de Sousa、Valéry Larue、Thierry Cresteil、Frédéric Dardel、Isabelle Artaud、Thierry Meinnel

  DOI：10.1021/jm060910c

  日期：2007.1.1

  New classes of antibiotics are urgently needed to counter increasing levels of pathogen resistance. Peptide deformylase (PDF) was originally selected as a specific bacterial target, but a human homologue, the inhibition of which causes cell death, was recently discovered. We developed a dual-screening strategy for selecting highly effective compounds with low inhibition effect against human PDF. We selected a new scaffold in vitro that discriminated between human and bacterial PDFs. Analyses of structure-activity relationships identified potent antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the same mode of action in vivo as previously identified PDF inhibitors but without the apoptotic effects of these inhibitors in human cells.