apratoxin S7 | 1414314-24-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: apratoxin S7
• 英文别名: (3S,5S,7S,10S,16S,19S,22S,27S)-16-[(2S)-butan-2-yl]-7-tert-butyl-3-hydroxy-22-[(4-methoxyphenyl)methyl]-5,17,19,20-tetramethyl-8-oxa-29-thia-14,17,20,23,30-pentazatricyclo[25.2.1.010,14]triacont-1(30)-ene-9,15,18,21,24-pentone
• CAS: 1414314-24-1
• 化学式: C₄₃H₆₇N₅O₈S
• 分子量: 814.1
• InChiKey: OLXQPAZGLQOODL-IKZWPYSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  57
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  183
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(1S)-3-allyloxycarbonyl-1-[(triphenylmethylthio)methyl]propylcarbamoyl]-1-tert-butyl-5-hydroxy-3-methylhex-1-yl}ester 1-(9H-fluoren-9-ylmethyl)ester 在 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 三氟甲磺酸酐 、 ammonium acetate 、 二乙胺 、 N,N-二异丙基乙胺 、 N-甲基苯胺 、 三苯基氧化膦 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 、 锌 作用下， 以 四氢呋喃 、 吡啶 、 水 、 乙腈 为溶剂， 反应 20.0h， 生成 apratoxin S7
  参考文献：
  名称：

  Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity

  摘要：

  Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/ E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound la and newly designed analogues apratoxins S7-S9 (1b-d), with various degrees of methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently synthesized utilizing improved procedures. Optimizations have been applied to the synthesis of key intermediate aldehyde 7 and further include the application of Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d) exhibited increased activity with subnanomolar potency. Apratoxin S8 (lc) lacks the propensity to be deactivated by dehydration and showed efficacy in a human HCT116 xenograft mouse model.

  DOI：

  10.1021/jm4019965

文献信息

• [EN] MACROCYCLIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE, AND METHODS OF TREATMENT<br/>[FR] AGENTS THÉRAPEUTIQUES MACROCYCLIQUES, DES MÉTHODES DE FABRICATION, ET MÉTHODES DE TRAITEMENT
  申请人：UNIV FLORIDA

  公开号：WO2015127161A1

  公开（公告）日：2015-08-27

  The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.

  本发明描述了具有治疗活性的大环化合物，以及治疗自身免疫疾病、炎症、癌症、肿瘤和与细胞增殖有关的疾病的机制和方法。
• MACROCYCLIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE, AND METHODS OF TREATMENT
  申请人：University of Florida Research Foundation

  公开号：EP3107919B1

  公开（公告）日：2021-01-27
• MACROCYCLIC THERAPEUTIC AGENTS AND METHODS OF TREATMENT
  申请人：Luesch Hendrik

  公开号：US20140088016A1

  公开（公告）日：2014-03-27

  The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.
• US9181304B2
  申请人：——

  公开号：US9181304B2

  公开（公告）日：2015-11-10
• [EN] MACROCYCLLC THERAPEUTIC AGENTS AND METHODS OF TREATMENT<br/>[FR] AGENTS THÉRAPEUTIQUES MACROCYCLIQUES ET PROCÉDÉS DE TRAITEMENT
  申请人：UNIV FLORIDA

  公开号：WO2012158933A2

  公开（公告）日：2012-11-22

  The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.