H-Py-Py-Py-OMe hydrochloride | 162085-96-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: H-Py-Py-Py-OMe hydrochloride
• 英文别名: Methyl 4-[[4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carboxylate
• CAS: 162085-96-3
• 化学式: C₁₉H₂₂N₆O₄
• 分子量: 398.421
• InChiKey: JWTWIBKFNXQMLY-UHFFFAOYSA-N

物化性质

• 沸点：
  528.7±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  H-Py-Py-Py-OMe hydrochloride 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Hairpin versus Extended DNA Binding of a Substituted β-Alanine Linked Polyamide

  摘要：

  A series of alpha-substituted beta-alanine (beta*) linked polyamides (DbaPyPyPy-beta*-PyPyPy) were prepared and examined. This resulted in the observation that while most substituents disrupt DNA binding, (R)-alpha-methoxy-beta-alanine (beta((R)-OMe)) maintains strong binding affinity and preferentially adopts a hairpin versus extended binding mode, providing an alternative hairpin linker to gamma-aminobutyric acid (gamma). A generalized variant of a fluorescent intercalator displacement assay conducted on a series of hairpin deoxyoligonucleotides containing a systematically varied A/T-rich binding site size was developed to distinguish between the extended binding of the parent beta-alanine 1 (DbaPyPyPy-beta-PyPyPy) and the hairpin binding of 3 (DbaPyPyPy-beta((R)-OMe)-PyPyPy).

  DOI：

  10.1021/ja0122039
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-羧酸 在 palladium on activated charcoal 硫酸 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 48.0h， 生成 H-Py-Py-Py-OMe hydrochloride
  参考文献：
  名称：

  Distamycin Analogues without Leading Amide at Their N-Termini − Comparative Binding Properties to AT- and GC-Rich DNA Sequences

  摘要：

  DOI：

  10.1002/1099-0690(200211)2002:21<3604::aid-ejoc3604>3.0.co;2-x

文献信息

• Synthesis and cytotoxicity evaluation of novel C7–C7, C7–N3 and N3–N3 dimers of 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benzo[e]indole (seco-CBI) with pyrrole and imidazole polyamide conjugates
  作者：Rohtash Kumar、J. William Lown

  DOI：10.1039/b303650m

  日期：——

  The C7–C7, C7–N3 and N3–N3 dimers of 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benzo[e]indole (seco-CBI) with pyrrole and imidazole polyamides were synthesized and preliminary anti-cancer evaluation carried out by NCI against three types of cancer cells.

  合成了1-氯甲基-5-羟基-1,2-二氢-3H-苯并[e]吲哚（seco-CBI）与吡咯和咪唑聚酰胺的C7–C7、C7–N3和N3–N3二聚体，并通过NCI对三种类型的癌细胞进行了初步抗癌评估。
• Total Synthesis of Distamycin A and 2640 Analogues:  A Solution-Phase Combinatorial Approach to the Discovery of New, Bioactive DNA Binding Agents and Development of a Rapid, High-Throughput Screen for Determining Relative DNA Binding Affinity or DNA Binding Sequence Selectivity
  作者：Dale L. Boger、Brian E. Fink、Michael P. Hedrick

  DOI：10.1021/ja994192d

  日期：2000.7.1

  solution-phase synthesis of distamycin A and its extension to the preparation of 2640 analogues are described. Thus, solution-phase synthesis techniques with reaction workup and purification employing acid/base liquid−liquid extractions were used in the multistep preparation of distamycin A (8 steps, 40% overall yield) and a prototypical library of 2640 analogues providing intermediates and final products that

  描述了远霉素 A 的液相合成的发展及其对 2640 类似物制备的扩展。因此，采用酸/碱液-液萃取进行反应后处理和纯化的液相合成技术用于多步制备偏霉素 A（8 步，40% 总产率）和 2640 类似物的原型库，提供中间体和最终产品在常规反应规模上纯度≥95%。公开了一种简单、快速和高通量的 DNA 结合亲和力筛选的补充开发，该筛选基于来自预结合溴化乙锭置换的荧光损失，适用于评估对 DNA 均聚物或特定序列的相对或绝对结合亲和力。发夹寡核苷酸）。使用发夹寡核苷酸，
• Bisindolylmaleimides Linked to DNA Minor Groove Binding Lexitropsins:  Synthesis, Inhibitory Activity against Topoisomerase I, and Biological Evaluation
  作者：Guojian Xie、Rajan Gupta、Kevin Atchison、J. William Lown

  DOI：10.1021/jm950465d

  日期：1996.1.1

  The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of oligopeptide-substituted bisindolylmaleimides 7-12 are described. Compounds 7-9, which contain a basic C-terminus function such as (dimethylamino)propyl and bind to DNA with C(50) values of 200, 160, and 135 microM, respectively, exhibited inhibition of topoisomerase I in a concentration

  描述了合成，表征，对拓扑异构酶I的抑制活性以及一系列寡肽取代的双吲哚基马来酰亚胺7-12的生物学评估。化合物7-9含有基本的C末端功能，例如（二甲氨基）丙基，并与C（50）值分别为200、160和135 microM的DNA结合，以浓度依赖的方式抑制了拓扑异构酶I 。同样，在<或= 100 microM浓度下观察到的拓扑异构酶I抑制的相对顺序为9> 8> 7，对应于寡肽部分中吡咯单元数量的增加。含有静电中性部分（例如甲酯）的化合物10-12不会与DNA模板结合，也不会抑制拓扑异构酶I。但是，这些化合物的细胞毒性活性为1。
• DNA binding agents with a minor groove binding tail
  申请人：Board of Regents, The University of Texas System

  公开号：US10358439B2

  公开（公告）日：2019-07-23

  Provided herein are compounds which intercalate into the DNA of a cell and are capable of crossing the blood brain barrier of a formula provided herein. Pharmaceutical compositions of the compounds and methods of treating cancer, for example brain, lung, or pancreatic cancer, are also provided herein.

  本文提供的化合物可插入细胞的 DNA 中，并能通过本文所提供配方的血脑屏障。本文还提供了这些化合物的药物组合物和治疗癌症（例如脑癌、肺癌或胰腺癌）的方法。
• Facile synthesis of oligopeptide distamycin analogs devoid of hydrogen bond donors or acceptors at the N-terminus: sequence-specific duplex DNA binding as a function of peptide chain length
  作者：Santanu Bhattacharya、Mini Thomas

  DOI：10.1016/s0040-4039(00)00802-9

  日期：2000.7

  The first examples of distamycin analogs, which lack hydrogen bond interactor groups at the N-terminus, have been synthesized. The bispyrrole peptide did not exhibit any detectable binding with double-stranded (ds) DNA. However, all other homologues did bind to ds-DNA strongly, with the binding affinities increasing as a function of the number of repeating pyrrole carboxamide units, implying that a hydrogen bond donor or acceptor atom per se at the N-terminus is not essential for their DNA binding. Studies with poly d(GC) showed that the N-terminal formamide is not a prerequisite for GC binding, contrary to earlier postulations. (C) 2000 Elsevier Science Ltd. All rights reserved.