3-(3-azido-1-propyl)-5-nitro-1H-indole | 950670-03-8

• 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: 3-(3-azido-1-propyl)-5-nitro-1H-indole
• 英文别名: 3-(3-azidopropyl)-5-nitro-1H-indole
• CAS: 950670-03-8
• 化学式: C₁₁H₁₁N₅O₂
• 分子量: 245.241
• InChiKey: ODIZPDTUEMQZDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  76
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-azido-1-propyl)-5-nitro-1H-indole 、 (1R,3R,4R,5S)-3-[2-O-benzoyl-3-O-((1S)-1-carboxy-2-cyclohexylethyl)-(β-D-galactopyranosyl)oxy]-4-[(α-L-fucopyranosyl)oxy]-5-methyl-N-(prop-2-yn-1-yl)cyclohexanecarboxamide 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 以68%的产率得到(1R,3R,4R,5S)-3-[2-O-benzoyl-3-O-((1S)-1-carboxy-2-cyclohexylethyl)-(β-D-galactopyranosyl)oxy]-4-[(α-L-fucopyranosyl)oxy]-5-methyl-N-({1-[3-(6-nitro-1H-indol-3-yl)propyl]-1H-1,2,3-triazol-4-yl}methyl)cyclohexanecarboxamide
  参考文献：
  名称：

  Nanomolar E-Selectin Antagonists with Prolonged Half-Lives by a Fragment-Based Approach

  摘要：

  Selectins, a family of C-type lectins, play a key role in inflammatory diseases (e.g., asthma and arthritis). However, the only millimolar affinity of sialyl Lewis(x) (sLe(x)), which is the common tetrasaccharide epitope of all physiological selectin ligands, has been a major obstacle to the development of selectin antagonists for therapeutic applications. In a fragment-based approach guided by NMR, ligands binding to a second site in close proximity to a sLe(x) mimic were identified. A library of antagonists obtained by connecting the sLe(x) mimic to the best second-site ligand via triazole linkers of different lengths was evaluated by surface plasmon resonance. Detailed analysis of the five most promising candidates revealed antagonists with K-D values ranging from 30 to 89 nM. In contrast to carbohydratelectin complexes with typical half-lives (t(1/2)) in the range of one second or even less, these fragment-based selectin antagonists show t(1/2) of several minutes. They exhibit a promising starting point for the development of novel anti-inflammatory drugs.

  DOI：

  10.1021/ja4029582
• 作为产物：
  描述：

  3-(3-Bromopropyl)-5-nitro-1H-indole 在 sodium azide 、 15-冠醚-5 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以93%的产率得到3-(3-azido-1-propyl)-5-nitro-1H-indole
  参考文献：
  名称：

  基于片段的原位组合方法可识别未知结合位点的高亲和力配体

  摘要：

  潜在客户：鉴定配体的标题方法特别适用于很少或没有结构信息的结合位点。在基于片段的方法中，通过NMR实验确定了合适的一对第一位和第二位配体。通过应用受体介导的原位组合方法，然后将两个配体连接起来以生成新的高亲和力铅结构（参见图片）。

  DOI：

  10.1002/anie.200907254

文献信息

• E-SELECTIN ANTAGONISTS
  申请人：Ernst Beat

  公开号：US20130331350A1

  公开（公告）日：2013-12-12

  Compounds, compositions and methods are provided for inhibiting in vitro and in vivo processes mediated by E-selectin binding. More specifically, particular glycomimetic compounds are described, wherein the compounds are E-selectin antagonists.

  本发明提供了用于抑制E-selectin结合介导的体外和体内过程的化合物、组合物和方法。更具体地，本发明描述了特定的糖类模拟化合物，其中这些化合物是E-selectin拮抗剂。
• METHOD FOR THE IDENTIFICATION OF NEW LEADS FOR DRUG CANDIDATES
  申请人：Universität Basel

  公开号：EP2013624B1

  公开（公告）日：2011-08-03
• Method for the Identification of New Leads for Drug Candidates
  申请人：Ernst Beat

  公开号：US20090239760A1

  公开（公告）日：2009-09-24

  Disclosed is a method for producing new leads for drug candidates. The method employs a combinatorial approach for identifying high affinity ligands. The target may be unknown and/or may include one or more unknown binding sites. A method involving a combined screening and synthesis method for bi-site inhibitors is disclosed comprising: 1) determining if there is sufficient proximity between ligands binding to different sites of a target: e.g. by using spin-labelled ligands quenching can be measured with NMR if a first ligand and second allosteric ligand are in proximity 2) connecting both ligands having linkers, via in situ synthesis in the presence of the protein scaffold (e.g. target guided synthesis combined with fragment based self assembly). Click chemistry is a preferred embodiment here. Also disclosed are kits used in context of this method, leads discovered by the method and their use in drug development. Leads for drugs acting on myelin associated glycoprotein (MAG) have been identified and synthesised.
• US8921328B2
  申请人：——

  公开号：US8921328B2

  公开（公告）日：2014-12-30
• [EN] METHOD FOR THE IDENTIFICATION OF NEW LEADS FOR DRUG CANDIDATES<br/>[FR] PROCÉDÉ D'IDENTIFICATION DE NOUVELLES TÊTES DE SÉRIE POUR DES MÉDICAMENTS CANDIDATS
  申请人：UNIV BASEL

  公开号：WO2007105094A1

  公开（公告）日：2007-09-20

  [EN] Disclosed is a method for producing new leads for drug candidates. The method employs a combinatorial approach for identifying high affinity ligands. The target may be unknown and/or may include one or more unknown binding sites. A method involving a combined screening and synthesis method for bi-site inhibitors is disclosed comprising: 1) determining if there is sufficient proximity between ligands binding to different sites of a target: e.g. by using spin-labelled ligands quenching can be measured with NMR if a first ligand and second allosteric ligand are in proximity 2) connecting both ligands having linkers, via in situ synthesis in the presence of the protein scaffold (e.g. target guided synthesis combined with fragment based self assembly). Click chemistry is a preferred embodiment here. Also disclosed are kits used in context of this method, leads discovered by the method and their use in drug development. Leads for drugs acting on myelin associated glycoprotein (MAG) have been identified and synthesised.
  [FR] La présente invention concerne un procédé de production de nouvelles têtes de série pour des médicaments candidats. Le procédé utilise une approche combinatoire pour identifier des ligands à affinité élevée. La cible peut être inconnue et/ou peut comprendre un ou des sites de liaison inconnus. L'invention concerne également un procédé comprenant un procédé combiné de criblage et de synthèse pour des inhibiteurs à deux sites comprenant: 1) la détermination de proximité suffisante entre des ligands de liaison à différents sites d'une cible, par exemple, au moyen de ligands marqués par spin, la désactivation peut être mesurée par la résonance magnétique nucléaire si un premier ligand et un second ligand allostérique sont en relation de proximité, 2) la connexion de deux ligands ayant des lieurs, par une synthèse in situ en présence de l'échafaudage protéinique interne (par exemple, une synthèse orientée vers la cible avec un auto-assemblage à base de fragments). La technique de liaison covalente désignée "click chemistry" constitue un mode de réalisation préféré de la présente invention. L'invention concerne également des trousses utilisées dans le cadre de ce procédé, des têtes de série découvertes par ce procédé et leur utilisation dans le développement de médicaments. Des têtes de série pour des médicaments agissant sur la glycoprotéine associée à la myéline (MAG) ont été identifiées et synthétisées.