3-[1-Methyl-4[1-methyl-4[1-methyl-4-formamidopyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidoxime | 203258-75-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-[1-Methyl-4[1-methyl-4[1-methyl-4-formamidopyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidoxime
• 英文别名: N-[5-[[5-[(3-amino-3-hydroxyiminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide
• CAS: 203258-75-7
• 化学式: C₂₂H₂₇N₉O₅
• 分子量: 497.514
• InChiKey: QPFBRXFLEPZDMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  190
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[1-Methyl-4[1-methyl-4[1-methyl-4-formamidopyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidoxime 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 4-amino-N-[5-[[5-[[(3E)-3-amino-3-hydroxyiminopropyl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide
  参考文献：
  名称：

  Cytotoxic α-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(00)00205-5
• 作为产物：
  描述：

  偏端霉素A盐酸盐 在 羟胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以52%的产率得到3-[1-Methyl-4[1-methyl-4[1-methyl-4-formamidopyrrole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidoxime
  参考文献：
  名称：

  Distamycin A和同类物的细胞毒性α-卤代丙烯酸衍生物。

  摘要：

  许多抗肿瘤药的作用机制都涉及DNA损伤，这可能是由于药物与DNA或与DNA结合蛋白的直接结合而引起的。但是，大多数DNA相互作用剂仅具有有限程度的序列特异性，这意味着它们可能击中所有细胞基因。DNA小沟结合剂（其中双霉素A的衍生物起着重要作用）由于与富含胸腺嘧啶-腺嘌呤（TA）的序列具有很高的选择性，可以显着改善癌症的治疗，增加基因特异性。我们现在报告和讨论合成的，体外和体内活性以及二霉素A的α-卤代丙烯酰胺基衍生物的一些机理特征。这项工作的最终结果是选择brostallicin 17（PNU-166196）。Brostallicin，目前处于II期临床试验中，与广谱霉素衍生物塔木斯汀相比，它具有广谱的抗肿瘤活性和更高的凋亡作用。与临床测试的DNA小沟结合剂相比，brostallicin的重要体外毒理学特征是对人类造血祖细胞的骨髓毒性与对肿瘤细胞的细胞毒性之间的比率非常高。brostall

  DOI：

  10.1021/jm031051k

文献信息

• 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broSTa href=https://www.molaid.com/MS_164855 target="_blank">TAllicin（PNU-166196）与TAM和其他MGB相比，显示出高的细胞毒性和骨髓毒性。BroSTa href=https://www.molaid.com/MS_164855 target="_blank">TAllicin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
• Acryloyl substituted distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents
  申请人：Pharmacia & Upjohn S.p.A.

  公开号：US20030023031A1

  公开（公告）日：2003-01-30

  According to the invention, there is provided a method of manufacturing a medicament for use in the treatment of cancer or viral infections which comprises obtaining a cancer treating effective amount of a compound of formula (I), 1 and combining the compound of formula (I) with at least one pharmaceutically acceptable excipient, and wherein the cancer treating effective amount of a compound of formula I is an acryloyl substituted distamycin derivative in which n, R 1 and R 2 , R 3 , B, are defined herein or a pharmaceutically acceptable salt thereof to produce a medicament for use in the treatment of cancer or viral infections.

  根据本发明，提供了一种制造治疗癌症或病毒感染的药物的方法，该方法包括获取公式（I）化合物的治疗癌症有效量，1并将公式（I）化合物与至少一种药用可接受的赋形剂结合，其中公式I化合物的治疗癌症有效量是一种丙烯酰基取代的二氨基链霉素衍生物，其中n，R1和R2，R3，B在此定义，或其药用可接受盐，以制备用于治疗癌症或病毒感染的药物。
• Design, Synthesis and Growth Inhibition Activity of Bis-Epoxyethyl Derivatives of Stallimycin Modified on the Amidino Moiety
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Giovanna Pavani、Francesca Fruttarolo、Delia Preti、Andrea Bovero、Mojgan Aghazadhe Tabrizi、Nicoletta Bianchi、Roberto Gambari

  DOI：10.1007/s00044-004-0034-6

  日期：2004.6

  Derivatives 3-6 of stallimycin (distamycin A) rnodified a t the C-terminal amidine moiety and tethered to a bis-epoxyethyl moiety (as DNA alkylating unit) at the N-terminal position have been prepared and tested for in vitro cytotoxic activity against two different leukemik cell lines, K562 and L1210. None of the compounds without epoxide was active. A comparison of the biological activity related to the diepoxy compounds 3-6 with different non-basic amidine modified moieties, showed low activity for the carbamoyl and N-methyl carbamoyl derivatives (compounds 5 and 6, respectively), moderate activity for the amidoxime analogue 4, good activity for the cyanamidine derivative 3.
• ACRYLOYL SUBSTITUTED DISTAMYCIN DERIVATIVES, PROCESS FOR PREPARING THEM, AND THEIR USE AS ANTITUMOR AND ANTIVIRAL AGENTS
  申请人：PHARMACIA & UPJOHN S.p.A.

  公开号：EP0915845B1

  公开（公告）日：2001-09-12
• US6482920B1
  申请人：——

  公开号：US6482920B1

  公开（公告）日：2002-11-19