17-(4-fluorobenzylamino)-17-demethoxygeldanamycin | 1025790-06-0

• 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-(4-fluorobenzylamino)-17-demethoxygeldanamycin
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-fluorophenyl)methylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
• CAS: 1025790-06-0
• 化学式: C₃₅H₄₄FN₃O₈
• 分子量: 653.748
• InChiKey: WVVIZGDAPXNYOI-YKNAKQMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  47
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  17-(4-fluorobenzylamino)-17-demethoxygeldanamycin 在 四甲基胍 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-12-(4-fluorophenyl)-15,13-dihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-1(6,4)-benzo[d]oxazolacycloheptadecaphane-4,6,10-trien-9-yl carbamate
  参考文献：
  名称：

  Cascade Transformation of the Ansamycin Benzoquinone Core into Benzoxazole Influencing Anticancer Activity and Selectivity

  摘要：

  DOI：

  10.1021/acs.joc.3c00493
• 作为产物：
  描述：

  对氟苄胺 、 格尔德霉素 以 二甲基亚砜 为溶剂， 反应 0.5h， 以89%的产率得到17-(4-fluorobenzylamino)-17-demethoxygeldanamycin
  参考文献：
  名称：

  Fluorine- and rhenium-containing geldanamycin derivatives as leads for the development of molecular probes for imaging Hsp90

  摘要：

  热休克蛋白90（Hsp90）是一种依赖ATP的分子伴侣，负责细胞内的蛋白质质量控制。已表明Hsp90在许多人​​类癌症中过度表达。这促使了对Hsp90抑制剂作为新型抗癌药物的广泛研究，最近还开发了用于体内成像Hsp90表达的分子探针。本工作描述了开发各种含氟和含铼的格尔德霉素衍生物，作为开发相应的18F标记和99mTc标记的PET和SPECT探针的先导化合物，用于分子成像Hsp90表达。所有化合物均在体外ATP酶活性测定中使用Hsp90同工型Hsp82p进行评估。氟苯甲酰基格尔德霉素衍生物5显示与母体化合物格尔德霉素相当的抑制效能。

  DOI：

  10.1039/c2ob25744k

文献信息

• Design, synthesis and biological evaluation of 17-arylmethylamine-17-demethoxygeldanamycin derivatives as potent Hsp90 inhibitors
  作者：Zhenyu Li、Lejiao Jia、Jifeng Wang、Xingkang Wu、Huilin Hao、Hongjiao Xu、Yunfei Wu、Guowei Shi、Chunhua Lu、Yuemao Shen

  DOI：10.1016/j.ejmech.2014.07.101

  日期：2014.10

  Thirty-three 17-arylmethylamine-substituted derivatives of geldanamycin (GA) were designed, synthesized and evaluated for the anti-proliferation activity on human cancer cell lines, LNCaP and MDA-MB-231. Three derivatives (22, 33 and 34) exhibited potent cytotoxicity with IC50 values range from 0.05 to 0.51 mu M against both cell lines. Hepatotoxicity test in mice demonstrated that the levels of both AST and ALT of 34-treated group were lower than that of 17-AAG group. Western blot assay indicated that 34 was more potent than 17-AAG in the down-regulation of Hsp90 client proteins CDK4, Her2, EGFR and Raf. Moreover, 34 showed excellent in vivo antitumor activity in the MDA-MB-231 xenograft nude mice, which is superior to 22 and 33, and 17-AAG, indicating that 34 was a promising antitumor candidate. Additionally, preliminary structure activity relationship (SAR) and molecular dynamics (MD) simulations of this new series of GA derivatives were also investigated, suggesting a theoretical model of 17-arylmethylamine geldanamycins binding to Hsp90. (C) 2014 Elsevier Masson SAS. All rights reserved.