desformyldistamycin A | 6576-31-4

• 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: desformyldistamycin A
• 英文别名: desformyldistamycin；distamycin；4-amino-N-[5-[[5-[(3-amino-3-imino-propyl)carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]-1-methyl-pyrrole-2-carboxamide；4-amino-N-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide
• CAS: 6576-31-4
• 化学式: C₂₁H₂₇N₉O₃
• 分子量: 453.504
• InChiKey: HHASBDZCPGTUKJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  178
• 氢给体数：
  6
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  desformyldistamycin A 在 sodium periodate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-[[(E)-3-[4-(2-chloroethylsulfinyl)phenyl]prop-2-enoyl]amino]-1-methylpyrrole-2-carboxamide
  参考文献：
  名称：

  二霉素A的苯硫芥末衍生物。

  摘要：

  描述了新型的二水霉素A的苯甲酰基和肉桂酰基硫芥末衍生物的设计，合成和细胞毒性，并讨论了结构活性关系。尽管烷基化能力较低，但这些硫芥末比相应的氮芥末具有更强的细胞毒性，而它们的亚砜类似物基本上没有活性。肉桂酰基硫芥子油衍生物（7）被证明是最有效的由二霉素产生的细胞毒素之一，效力比美法仑高约1000倍。

  DOI：

  10.1016/s0960-894x(00)00295-x
• 作为产物：
  描述：

  司他霉素 在 盐酸 作用下， 以 甲醇 为溶剂， 以89%的产率得到desformyldistamycin A
  参考文献：
  名称：

  Anti-HIV-I activity of linked lexitropsins

  摘要：

  Five groups of lexitropsin oligopeptides have been synthesized that are structurally related to the natural antiviral agents netropsin and distamycin and bearing two such moieties joined by flexible or rigid linkers. Inhibitory activity of these types of agents against murine leukemia retrovirus (MuLV) led to an evaluation of their inhibition of HIV-I in cell culture. The antiretroviral activity of the five different classes of lexitropsins is discussed in terms of their structural differences.

  DOI：

  10.1021/jm00093a023

文献信息

• 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，
• [EN] PROCESS FOR THE SYNTHESIS OF DISTAMYCIN AND DERIVATIVES THEREOF USING 1-METHYL-4-FORMYLAMINO-2-PYRROLECARBONYL CHLORIDE ITERATIVELY AS AN INTERMEDIATE<br/>[FR] PROCEDE DE SYNTHESE DE DISTAMYCINE ET DE SES DERIVES AU MOYEN DE CHLORURE DE 1-METHYL-4-FORMYLAMINO-2-PYRROLECARBONYLE DE FACON REPETEE EN TANT QU'INTERMEDIAIRE
  申请人：NAXOSPHARMA S R L

  公开号：WO2004106301A1

  公开（公告）日：2004-12-09

  A process for the total synthesis of Distamycin, and synthetic poly-(4 aminopyrrole -2-carboxamide) congeners thereof, using 1-methyl-4­- forinylamino-2-pyrrolecarbonyl chloride iteratively as an intermediate, is provided. The process finds application for both in solution and solid support synthetic technologies.

  提供了一种使用1-甲基-4-吡啶基氨基-2-吡咯烷羧酰氯作为中间体迭代地进行Distamycin的全合成以及合成的聚合物-(4-氨基吡咯-2-羧酰胺)的方法。该方法适用于溶液和固相合成技术。
• The discovery of a new potential anticancer drug: a case history
  作者：Paolo Cozzi

  DOI：10.1016/s0014-827x(03)00014-4

  日期：2003.3

  represent a class of anticancer agents whose DNA sequence specificity was hypothesized to lead to high selectivity of action. Tallimustine (TAM), a benzoyl nitrogen mustard derivative of distamycin A (DST), showed excellent antitumor activity in preclinical tests, but also a severe myelotoxicity. Novel nitrogen mustard, nitrogen half-mustard and sulfur mustard derivatives of DST showing excellent activity

  DNA小沟结合剂（MGB）代表一类抗癌药物，据推测其DNA序列特异性可导致较高的作用选择性。他莫司汀A（DST）的苯甲酰氮芥子气衍生物塔利莫司（TAM）在临床前测试中显示出优异的抗肿瘤活性，但同时也具有严重的骨髓毒性。最近发现了DST的新型氮芥，氮半芥末和硫芥末衍生物，它们显示出优异的活性，并报道了SAR。特别地，作为单臂烷基化剂的氮半芥末和硫芥末衍生物代表了令人感兴趣的结构新颖性。另一类新的细胞毒性抗癌药是DST样寡肽的α-卤代丙烯酰胺衍生物，与TAM相比，其活性明显提高。特别地，以胍基部分结束的α-溴-丙烯酰胺基四吡咯衍生物brostallicin（PNU-166196）与TAM和其他MGB相比，显示出高的细胞毒性和骨髓毒性。Brostallicin与小沟结合，但在经典的体外DNA烷基化测定中似乎无反应。关于明显缺乏DNA烷基化的现象，我们推测细胞内亲核试剂（例如谷胱甘肽（GSH））可
• Cytotoxic α-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety
  作者：Paolo Cozzi、Italo Beria、Marina Caldarelli、Cristina Geroni、Nicola Mongelli、Giulia Pennella

  DOI：10.1016/s0960-894x(00)00205-5

  日期：2000.6

  The design, synthesis, in vitro and in vivo activities of novel alpha-bromoacrylic derivatives of distamycin A, modified at the amidino moiety by the replacement with basic or non-basic groups are reported. In spite of the relevance of these modifications of distamycin frame, the new derivatives are potent cytotoxics. The presence of the amidino moiety, is, therefore, not an absolute requirement for the activity. In particular due to a favorable myclotoxicity/cytotoxicity ratio, guanidino derivative PNU 166196 was selected for clinical development. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Anti-HIV-I activity of linked lexitropsins
  作者：Wuyi Wang、J. William Lown

  DOI：10.1021/jm00093a023

  日期：1992.7

  Five groups of lexitropsin oligopeptides have been synthesized that are structurally related to the natural antiviral agents netropsin and distamycin and bearing two such moieties joined by flexible or rigid linkers. Inhibitory activity of these types of agents against murine leukemia retrovirus (MuLV) led to an evaluation of their inhibition of HIV-I in cell culture. The antiretroviral activity of the five different classes of lexitropsins is discussed in terms of their structural differences.