17-(4-iodobenzylamino)-17-demethoxygeldanamycin | 1622011-48-6

• 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-iodobenzylamino)-17-demethoxygeldanamycin
• 英文别名: (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-19-((4-iodobenzyl)amino)-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；[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-19-[(4-iodophenyl)methylamino]-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: 1622011-48-6
• 化学式: C₃₅H₄₄IN₃O₈
• 分子量: 761.654
• InChiKey: DDOQRRKJIARQTN-YKNAKQMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 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：
  9

反应信息

• 作为反应物：
  描述：

  17-(4-iodobenzylamino)-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)-15,13-dihydroxy-12-(4-iodophenyl)-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：

  4-碘苄胺 、 格尔德霉素 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 17-(4-iodobenzylamino)-17-demethoxygeldanamycin
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 17-arylmethylamine-17-demethoxygeldanamycin derivatives as potent Hsp90 inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2014.07.101

文献信息

• Regioselective approach to colchiceine tropolone ring functionalization at C(9) and C(10) yielding new anticancer hybrid derivatives containing heterocyclic structural motifs
  作者：Krystian Pyta、Natalia Skrzypczak、Piotr Ruszkowski、Franz Bartl、Piotr Przybylski

  DOI：10.1080/14756366.2022.2028782

  日期：2022.12.31

  C(9)/C(10) “click” modifications within the tropolone ring of colchiceine (2) is investigated. New ether derivatives of 2, bearing alkyne, azide, vinyl, or halide aryl groups enable assembly of the alkaloid part with heterocycles or important biomolecules such as saccharides, geldanamycin or AZT into hybrid scaffolds by dipolar cycloaddition (CuAAC) or Heck reaction. Compared to colchicine (1) or colchiceine

  摘要 研究了碱基类型、温度和溶剂对秋水仙碱 ( 2 )托酚酮环内区域选择性 C(9)/C(10) “点击”修饰的影响。带有炔烃、叠氮化物、乙烯基或卤代芳基的2的新醚衍生物能够通过偶极环加成 (CuAAC) 或 Heck 反应将生物碱部分与杂环或重要的生物分子如糖类、格尔德霉素或 AZT 组装成杂化支架。与秋水仙碱 ( 1 ) 或秋水仙碱 ( 2 ) 相比，醚同系物，例如3e [IC 50 s ( 3e)∼ 0.9 nM]，显示出改善或相似的抗癌作用，由此证明取代基的体积和托酚酮的取代模式是必不可少的。生物学研究表明，通过末端碱性杂环如喹啉或吡啶扩展醚臂，可降低 HDF 细胞的高抗癌效力（IC 50 s ~ 1-2 nM）的毒性。将醚和杂化衍生物对接到 α GTP /β 微管蛋白二聚体的秋水仙碱口袋中揭示了有利的结合模式和有吸引力的抗癌效力之间的关系。
• 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.
• 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