17,18-diazepino-17-demethoxygeldanamycin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 17,18-diazepino-17-demethoxygeldanamycin
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,27-dioxo-2,20,24-triazatricyclo[16.8.1.019,25]heptacosa-1(26),4,6,10,18,24-hexaen-9-yl] carbamate
• 化学式: C₃₁H₄₄N₄O₇
• 分子量: 584.713
• InChiKey: ADZJVFOKMMVPKF-ZOMYCCNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.63
• 重原子数：
  42.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  161.57
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  17-(3-aminopropylamino)-17-demethoxygeldanamycin 在 silica gel 作用下， 以 水 为溶剂， 生成 17,18-diazepino-17-demethoxygeldanamycin
  参考文献：
  名称：

  适用于药物递送系统的17-取代的氨基烷基格尔德霉素衍生物的合成和评估得到改进。

  摘要：

  用1，3-二氨基丙烷和1，3-二氨基-2-羟基丙烷取代格尔德霉素的17-甲氧基，以引入可用于与靶向部分和药物载体缀合的伯氨基。我们已经开发了一种程序，该程序提供了改进的合成产率和重现性。两种格尔德霉素衍生物均显示出对人卵巢癌细胞系A2780的抗增殖活性。

  DOI：

  10.1016/s0960-894x(01)00374-2

文献信息

• Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives
  作者：R. C. Schnur、M. L. Corman、R. J. Gallaschun、B. A. Cooper、M. F. Dee、J. L. Doty、M. L. Muzzi、J. D. Moyer、C. I. DiOrio

  DOI：10.1021/jm00019a010

  日期：1995.9

  The erbB-2 oncogene encodes a transmembrane protein tyrosine kinase which plays a pivotal role in signal transduction and has been implicated when overexpressed in breast, ovarian, and gastric cancers. Naturally occurring benzoquinoid ansamycin antibiotics herbimycin A, geldanamycin (GDM), and dihydrogeldanamycin were found to potently deplete p185, the erbB-2 oncoprotein, in human breast cancer SKBR-3 cells in culture. Chemistry efforts to modify selectively the quinoid moiety of GDM afforded derivatives with greater potency in vitro and in vivo. Analogs demonstrated inhibition of p185 phosphotyrosine in cell culture and in vivo after systemic drug administration to nu/nu nude mice bearing Fisher rat embryo cells transfected with human erbB-2 (FRE/erbB-2). Specifically, dosed intraperitoneally at 100 mg/kg, 17-(allylamino)-17-demethoxygeldanamycin and other 17-amino analogs were effective at reducing p185 phosphotyrosine in subcutaneous flank FRE/erbB-2 tumors. Modifications to the 17-19-positions of the quinone ring revealed a broad structure-activity relationship in vitro.
• Improved synthesis and evaluation of 17-substituted aminoalkylgeldanamycin derivatives applicable to drug delivery systems
  作者：Yuji Kasuya、Zheng-Rong Lu、Pavla Kopečková、Jindřich Kopeček

  DOI：10.1016/s0960-894x(01)00374-2

  日期：2001.8

  The 17-methoxy group of geldanamycin was substituted with 1,3-diaminopropane and 1,3-diamino-2-hydroxypropane to introduce a primary amino group useful for conjugation with targeting moieties and drug carriers. We have developed a procedure that has provided improved yield and reproducibility of the syntheses. Both geldanamycin derivatives demonstrated antiproliferative activity towards the human ovarian

  用1，3-二氨基丙烷和1，3-二氨基-2-羟基丙烷取代格尔德霉素的17-甲氧基，以引入可用于与靶向部分和药物载体缀合的伯氨基。我们已经开发了一种程序，该程序提供了改进的合成产率和重现性。两种格尔德霉素衍生物均显示出对人卵巢癌细胞系A2780的抗增殖活性。