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.
• Fluorine- and rhenium-containing geldanamycin derivatives as leads for the development of molecular probes for imaging Hsp90
  作者：Frank Wuest、Vincent Bouvet、BaoChan Mai、Paul LaPointe

  DOI：10.1039/c2ob25744k

  日期：——

  Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone responsible for protein quality control in cells. Hsp90 has been shown to be overexpressed in many human cancers. This has prompted extensive research on Hsp90 inhibitors as novel anticancer agents and, more recently, the development of molecular probes for imaging Hsp90 expression in vivo. This work describes the development of various fluorine-containing and rhenium-containing geldanamycin derivatives as leads for the development of corresponding 18F-labeled and 99mTc-labeled PET and SPECT probes for molecular imaging of Hsp90 expression. All compounds were evaluated in an in vitro ATPase activity assay using Hsp90 isoform Hsp82p. Fluorobenzoylated geldanamycin derivative 5 displayed comparable inhibitory potency like parent compound geldanamycin.

  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。
• Cascade Transformation of the Ansamycin Benzoquinone Core into Benzoxazole Influencing Anticancer Activity and Selectivity
  作者：Natalia Skrzypczak、Krystian Pyta、Wiktor Bohusz、Aleksandra Leśniewska、Maria Gdaniec、Piotr Ruszkowski、Wojciech Schilf、Franz Bartl、Piotr Przybylski

  DOI：10.1021/acs.joc.3c00493

  日期：2023.7.7