2'-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-[2,4'-bithiazole]-4-carboxylic acid | 308849-82-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2'-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-[2,4'-bithiazole]-4-carboxylic acid
• 英文别名: 2'-[(9-fluorenylmethoxycarbonyl)amino]ethyl-2,4'-bithiazole-4-carboxylic acid；[2'-(fluorenylmethoxycarbonyl)amino]ethyl-2,4'-bithiazole-4-carboxylic acid；2-[2-[2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]-1,3-thiazol-4-yl]-1,3-thiazole-4-carboxylic acid
• CAS: 308849-82-3
• 化学式: C₂₄H₁₉N₃O₄S₂
• 分子量: 477.565
• InChiKey: ZYNPKCPVQSKTFK-UHFFFAOYSA-N

物化性质

• 熔点：
  171-173 °C
• 密度：
  1.424±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2'-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-[2,4'-bithiazole]-4-carboxylic acid 在 哌啶 、 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-((2-(4-((3-((tert-butoxycarbonyl)amino)propyl)carbamoyl)-[2,4'-bithiazol]-2'-yl)ethyl)amino)-4-oxobutanoic acid
  参考文献：
  名称：

  [EN] NEOMYCIN BASED COMPOUNDS, AND PHARMACEUTICAL USE THEREOF
  [FR] COMPOSÉS À BASE DE NÉOMYCINE ET LEUR UTILISATION PHARMACEUTIQUE

  摘要：

  本发明涉及医学领域，特别是肿瘤学领域。特别是，提供了在治疗各种癌症，如胶质母细胞瘤、结直肠癌或乳腺癌方面有用的新化合物。本公开还涉及含有所述化合物的药物组合物。

  公开号：

  WO2021064052A1
• 作为产物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 2'-(2-Aminoethyl)-2,4'-bithiazole-4-carboxylic acid hydrochloride 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以72%的产率得到2'-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-[2,4'-bithiazole]-4-carboxylic acid
  参考文献：
  名称：

  博莱霉素类抗生素的固相合成。108 人去糖霉素文库的构建

  摘要：

  博来霉素 (BLM) 是从轮状链霉菌中分离出的结构相关的糖肽抗生素，可介导 DNA 和 RNA 的序列选择性氧化损伤。去糖博来霉素缺乏碳水化合物部分，可以像博来霉素本身一样切割 DNA，尽管效力较低，并且已成功用于分析博来霉素的功能域。尽管已经报道了对博来霉素和去甘博来霉素的结构修饰，但尚未描述具有增强的 DNA 切割活性的博来霉素或去甘博来霉素类似物。在固体支持物上成功合成了去甘博莱霉素，允许通过平行固相合成轻松固相合成 108 种独特的去甘博莱霉素类似物。每种去糖博莱霉素类似物都被有效合成；通过HPLC积分确定每种粗产物的纯度大于60%。去糖博莱霉素库的固相合成提供了接近毫克到毫克的每种去糖博莱霉素，从而允许通过 (1) H NMR 和高分辨率质谱法进行表征。每个类似物都表现出高于背景切割的超螺旋质粒 DNA 松弛；该文库包括两种类似物，它们比亲本去糖霉素分子在更大程度上介导质粒松弛。

  DOI：

  10.1021/ja021388w

文献信息

• Solid-Phase Synthesis of Bleomycin A₅ and Three Monosaccharide Analogues:  Exploring the Role of the Carbohydrate Moiety in RNA Cleavage
  作者：Craig J. Thomas、Alexander O. Chizhov、Christopher J. Leitheiser、Michael J. Rishel、Kazuhide Konishi、Zhi-Fu Tao、Sidney M. Hecht

  DOI：10.1021/ja0208916

  日期：2002.11.1

  A5) and three monosaccharide analogues is presented. The monosaccharide analogues incorporated alpha-d-mannose, alpha-l-gulose, and alpha-l-rhamnose moieties in lieu of the disaccharide normally present in BLM A5. Also explored were the abilities of each of the monosaccharide congeners to cleave a 53-nt RNA. The elaboration of these carbohydrate-modified bleomycin analogues helps to define the role of

  介绍了博来霉素 A5 (BLM A5) 和三种单糖类似物的固相合成。单糖类似物加入了 α-d-甘露糖、α-l-古洛糖和 α-l-鼠李糖部分，代替了 BLM A5 中通常存在的二糖。还研究了每种单糖同源物切割 53-nt RNA 的能力。这些碳水化合物修饰的博来霉素类似物的详细说明有助于确定二糖部分在 RNA 裂解过程中的作用。博来霉素 A5 和每种碳水化合物类似物的相对容易的固相合成构成了博来霉素持续机理研究的重要进展。
• Solid-phase synthesis and biochemical evaluation of conformationally constrained analogues of deglycobleomycin A 5
  作者：Ali Cagir、Zhi-Fu Tao、Steven J Sucheck、Sidney M Hecht

  DOI：10.1016/j.bmc.2003.08.033

  日期：2003.11

  Deglycobleomycin binds to and degrades the self-complementary oligonucleotide d(CGCTAGCG)(2) in a sequence selective fashion. A previous modeling study [J. Am. Chem. Soc. 120, (1998), 7450] had shown that, during binding to double stranded DNA, the conformation of the methylvalerate domain of deglycoBLM approximated that of S-proline. In the belief that an analogue of deglycoBLM structurally constrained

  Deglycobleomycin以序列选择性方式结合并降解自身互补寡核苷酸d（CGCTAGCG）（2）。以前的建模研究[J. 上午。化学 Soc。120，（1998），7450]已经表明，在与双链DNA结合期间，deglycoBLM的甲基戊酸酯结构域的构象接近于S-脯氨酸。认为在结构上受约束以模仿DNA结合的构象的deglycoBLM类似物可能表现出促进的DNA结合和裂解，因此制备了deglycoBLM类似物，其中戊酸甲酯部分被S-脯氨酸代替。该deglycoBLM类似物以及相关的含有R-脯氨酸的类似物在TentaGel树脂上合成。发现这两个类似物都能够结合Fe（2+）和激活O（2）转移到苯乙烯。然而，
• Deglycobleomycin A6 analogues modified in the methylvalerate moiety
  作者：Xiaoqing Cai、Paul A. Zaleski、Ali Cagir、Sidney M. Hecht

  DOI：10.1016/j.bmc.2011.04.047

  日期：2011.6

  Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A(5) using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A(5). Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage. (C) 2011 Published by Elsevier Ltd.
• Conformationally Constrained Analogues of Bleomycin A₅
  作者：Michael J. Rishel、Craig J. Thomas、Zhi-Fu Tao、Corine Vialas、Christopher J. Leitheiser、Sidney M. Hecht

  DOI：10.1021/ja030057w

  日期：2003.8.1

  The bleomycin (BLM) group antitumor antibiotics are glycopeptide-derived natural products shown to cause sequence selective lesions in DNA. Prior studies have indicated that the linker region, composed of the methylvalerate and threonine residues, may be responsible for a conformational bend in the agent required for efficient DNA cleavage. We have synthesized a number of conformationally constrained methylvalerate analogues and incorporated them into deglycobleomycin A(5) congeners using our recently reported procedure for the solid phase construction of (deglyco)bleomycin and its analogues. These analogues were designed to probe the effects of conformational constraint of the native valerate moiety. Initial experiments indicated that the constrained molecules, none of which mimic the conformation proposed for the natural valerate linker, possessed DNA cleavage activity, albeit with potencies less than that of (deglyco)BLM and lacking sequence selectivity. Further experiments demonstrated that these analogues failed to produce alkali-labile lesions in DNA or sequence selective oxidative damage in RNA. However, two of the conformationally constrained deglycoBLM analogues were shown to mediate RNA cleavage in the absence of added Fe2+. The ability of the analogues to mediate the oxygenation of small molecules was also assayed, and it was shown that they were as competent in the transfer of oxygen to low molecular weight substrates as the parent compound.
• NEOMYCIN BASED COMPOUNDS, AND PHARMACEUTICAL USE THEREOF
  申请人：UNIVERSITÉ COTE D'AZUR

  公开号：US20220395523A1

  公开（公告）日：2022-12-15

  The present invention relates to the field of medicine, in particular of oncology. Especially, it provides new compounds useful in the treatment of various cancers, such as glioblastoma, colorectal or breast cancers. The present disclosure also relates to pharmaceutical compositions containing the disclosed compounds.