Monomethyldistamycin A | 85407-11-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Monomethyldistamycin A
• 英文别名: N-[5-[[5-[(3-amino-3-methyliminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide
• CAS: 85407-11-0
• 化学式: C₂₃H₂₉N₉O₄
• 分子量: 495.541
• InChiKey: ZPICQTADFKQIRG-UHFFFAOYSA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  170
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Monomethyldistamycin A 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 N-(3-amino-3-methyliminopropyl)-4-[[4-[[4-[[4-(2-bromoprop-2-enoylamino)-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carbonyl]amino]-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：

  司他霉素 、 甲胺 以 N,N-二甲基甲酰胺 为溶剂， 生成 Monomethyldistamycin A
  参考文献：
  名称：

  一种新的潜在抗癌药的发现：案例历史。

  摘要：

  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

  DOI：

  10.1016/s0014-827x(03)00014-4

文献信息

• Synthesis and antiviral activity of distamycin A analogs: substitutions on the different pyrrole nitrogens and in the amidine function
  作者：Leif Grehn、Ulf Ragnarsson、Bertil Eriksson、Bo Oeberg

  DOI：10.1021/jm00361a018

  日期：1983.7

  Several new analogues of the antiviral antibiotic distamycin A were synthesized and assayed for their effects on influenza and herpes simplex virus. The new compounds 5b-j (R1-3 = H, CH3, and C2H5, R4,5 = H and CH3) were obtained via stepwise prepared formylated trimeric benzyl 4-aminopyrrole-2-carboxylates 3a-h, which after catalytic hydrogenolysis were coupled as N-succinimidyl esters directly with the proper beta-aminopropionamidine, unsubstituted or substituted with one or two methyl groups in the amidine function. Most of the new analogues did not exhibit significant effects on the viruses studied, but three compounds (5f-h) displayed activity on herpes virus as demonstrated in plaque formation and virus yield assays. Elevated cytotoxicity was simultaneously observed for 5g and 5h. For compound 5f, a partial separation of antiherpes activity and cytotoxicity was accomplished. The differences in antiherpes activity did not correspond to the differences in the inhibition of herpes virus DNA polymerase.
• 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.
• 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