ECBN*HCl

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ECBN*HCl
• 英文别名: ECBN hydrochloride；(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-18-amino-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-1,4,7,13,16,22-hexazatricyclo[22.3.0.09,13]heptacosane-2,5,8,14,17,23-hexone;hydrochloride
• 化学式: C₃₄H₅₁N₇O₁₅*ClH
• 分子量: 834.278
• InChiKey: FKIXKMLIKIOEJP-WJXYPMDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.88
• 重原子数：
  57.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  365.11
• 氢给体数：
  14.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  ECBN*HCl 、 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 生成
  参考文献：
  名称：

  棘皮菌素B的N-酰化类似物的合成和活性评估具有改善的溶解度和较低的毒性。

  摘要：

  目前，棘孢菌素被推荐作为治疗浸润性念珠菌病的一线药物。但是，低的口服生物利用度和溶解度限制了它们的应用。为了改善这种情况，本研究选择氨基酸和脂肪酸为原料来修饰棘皮菌素B的核。从具有强大的抗真菌活性和良好水溶性的衍生物中筛选出六个N-酰化的类似物。基于抗真菌药性和溶血毒性，候选化合物5具有良好的抗真菌活性且无溶血作用。而且，与阿尼芬净相比，化合物5显示出可比的杀真菌效果，更高的溶解度和更低的毒性。总之，化合物5 由于保留的抗真菌活性，高溶解度和低毒性，具有进一步研究和开发的潜力。

  DOI：

  10.1002/psc.3278

文献信息

• Commercialization and Late-Stage Development of a Semisynthetic Antifungal API: Anidulafungin/<scp>d</scp>-Fructose (Eraxis)
  作者：Timothy Norris、John VanAlsten、Stephen Hubbs、Marcus Ewing、Weiling Cai、Matthew L. Jorgensen、Jon Bordner、Grace O. Jensen

  DOI：10.1021/op800055h

  日期：2008.5.1

  Many years ago anidulafungin 1 was identified as a potentially useful medicine for the treatment of fungal infections. Its chemical and physical properties as a relatively high molecular weight semisynthetic derived from echinocandin B proved to be a significant hurdle to its final presentation as a useful medicine. It has recently been approved as an intravenous treatment for invasive candidaisis, an increasingly common health hazard that is potentially life-threatening. The development and commercialization of this API, which is presented as a molecular mixture of anidulafungin and D-fructose is described. This includes, single crystal X-ray structures of the starting materials, the echinocandin B cyclic-peptide nucleus (ECBN center dot HCl) and the active ester 1-([4 ''(pentyloxy)-1,1':4',1 ''-terphenyl-4-yl]carbonyl}oxy)-1,H-1,2,3-ben- zotriazole (TOBt). Details of the structure and properties of starting materials, scale-up chemistry and unusual crystallization phenomena associated with the API formation are discussed.
• The synthesis and activity evaluation of N‐acylated analogs of echinocandin B with improved solubility and lower toxicity
  作者：Bing Zhu、Yuanzhen Dong、Jie Ma、Minwei Chen、Sida Ruan、Wenjie Zhao、Jun Feng

  DOI：10.1002/psc.3278

  日期：2020.11

  improve this situation, this study chose amino acid and fatty acid as raw materials to modify the nucleus of echinocandin B. Six N‐acylated analogs were screened from the derivatives that possessed potent antifungal activity and good water solubility. Based on antifungal susceptibility and hemolytic toxicity, compound 5 as the candidate had good antifungal activity and no hemolytic effect. Moreover, compared

  目前，棘孢菌素被推荐作为治疗浸润性念珠菌病的一线药物。但是，低的口服生物利用度和溶解度限制了它们的应用。为了改善这种情况，本研究选择氨基酸和脂肪酸为原料来修饰棘皮菌素B的核。从具有强大的抗真菌活性和良好水溶性的衍生物中筛选出六个N-酰化的类似物。基于抗真菌药性和溶血毒性，候选化合物5具有良好的抗真菌活性且无溶血作用。而且，与阿尼芬净相比，化合物5显示出可比的杀真菌效果，更高的溶解度和更低的毒性。总之，化合物5 由于保留的抗真菌活性，高溶解度和低毒性，具有进一步研究和开发的潜力。