(6β,9β,13α,14β,20α)-2,3-dihydroxy-9,13-dimethyl-6-(nitromethyl)-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid | 1350630-32-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (6β,9β,13α,14β,20α)-2,3-dihydroxy-9,13-dimethyl-6-(nitromethyl)-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
• 英文别名: 6-(nitromethyl)dihydrocelastrol；(2R,4aS,6aR,6aS,8R,14aS,14bR)-10,11-dihydroxy-2,4a,6a,6a,9,14a-hexamethyl-8-(nitromethyl)-3,4,5,6,8,13,14,14b-octahydro-1H-picene-2-carboxylic acid
• CAS: 1350630-32-8
• 化学式: C₃₀H₄₁NO₆
• 分子量: 511.659
• InChiKey: PWMPMLPFFOITIJ-NVHHSDGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  37
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6β,9β,13α,14β,20α)-2,3-dihydroxy-9,13-dimethyl-6-(nitromethyl)-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid 在 palladium on activated charcoal 、 对甲苯磺酸 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 (6β,9β,13α,14β,20α)-2,3-[(1-methylethylidene)bis(oxy)]9,13-dimethyl-6-(aminomethyl)-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
  参考文献：
  名称：

  SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway

  摘要：

  Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent manner. Celastrol binding to Nur77 promotes Nur77 translocation from nucleus to cytoplasm, resulting in clearance of inflamed mitochondria and then alleviation of inflammation. Here, we report the design, synthesis, SAR study and biological evaluation of a series of celastrol analogs. A total of 24 celastrol derivatives were made. Compound 3a with a K-d of 0.87 mu M was found to be less toxic than celastrol and could be a hit molecule for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.009
• 作为产物：
  描述：

  硝基甲烷 、 雷公藤红素 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以36%的产率得到(6β,9β,13α,14β,20α)-2,3-dihydroxy-9,13-dimethyl-6-(nitromethyl)-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
  参考文献：
  名称：

  Remarkable Stereospecific Conjugate Additions to the Hsp90 Inhibitor Celastrol

  摘要：

  Celastrol, an important natural product and Hsp90 inhibitor with a wide range of biological and medical activities and broad use as a biological probe, acts by an as yet undetermined mode of action. It is known to undergo Michael additions with biological sulfur nucleophiles. Here it is demonstrated that nucleophiles add to the pharmacophore of celastrol in a remarkable stereospecific manner. Extensive characterization of the addition products has been obtained using NMR spectrometry, nuclear Overhauser effects, and density functional theory to determine facial selectivity and gain insight into the orbital interactions of the reactive centers. This stereospecificity of celastrol may be important to its protein target selectivity.

  DOI：

  10.1021/ja208359a

文献信息

• [EN] ANALOGS OF CELASTROL<br/>[FR] ANALOGUES DE CÉLASTROL
  申请人：ERX PHARMACEUTICALS INC

  公开号：WO2017070615A1

  公开（公告）日：2017-04-27

  Described herein, inter alia, are compositions and methods for treating or preventing obesity and using the same.

  本文描述了用于治疗或预防肥胖以及使用这些方法的组合物和方法。
• COMPOUNDS FOR THE TREATMENT OF OBESITY AND METHODS OF USE THEREOF
  申请人：The Children's Medical Center Corporation

  公开号：US20150274634A1

  公开（公告）日：2015-10-01

  Pentacyclic triterpene compounds are provided herein. Also provided are pharmaceutical formulations containing a therapeutically effective amount of one or more of the compounds, or pharmaceutically acceptable salts or prodrugs thereof, in combination with one or more pharmaceutically acceptable excipients. The pharmaceutical formulations can be administered to a pre-obese, obese, or morbidly obese patient to induce weight loss, reduce body fat, reduce food intake, improve glucose homeostasis, prevent obesity, or a combination thereof. The compounds can also be co-administered with leptin or a leptin analog.
• ANALOGS OF CELASTROL
  申请人：ERX Pharmaceuticals, Inc.

  公开号：US20210061851A1

  公开（公告）日：2021-03-04

  Described herein, inter alia, are compositions and methods for treating or preventing obesity and using the same.
• [EN] CELASTROL AND DERIVATIVES FOR THE TREATMENT OF OBESITY<br/>[FR] CÉLASTROL ET SES DÉRIVÉS POUR LE TRAITEMENT DE L'OBÉSITÉ
  申请人：CHILDRENS MEDICAL CENTER

  公开号：WO2015148802A1

  公开（公告）日：2015-10-01

  Pentacyclic triterpene compounds are provided herein. Also provided are pharmaceutical formulations containing a therapeutically effective amount of one or more of the compounds, or pharmaceutically acceptable salts or prodrugs thereof, in combination with one or more pharmaceutically acceptable excipients. The pharmaceutical formulations can be administered to a pre-obese, obese, or morbidly obese patient to induce weight loss, reduce body fat, reduce food intake, improve glucose homeostasis, prevent obesity, or a combination thereof. The compounds can also be co-administered with leptin or a leptin analog.