mitomycin-C | 69515-74-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: mitomycin-C
• 英文别名: mitomycin C；Mitomycin；6-amino-8-carbamoyloxymethyl-8a-methoxy-5-methyl-1,1a,2,8,8a,8b-hexahydro-azirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione；Azirino(2',3':3,4)pyrrolo(1,2-a)indole-4,7-dione, 6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-5-methyl-, carbamate；(11-amino-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl)methyl carbamate
• CAS: 69515-74-8；628317-17-9
• 化学式: C₁₅H₁₈N₄O₅
• 分子量: 334.332
• InChiKey: NWIBSHFKIJFRCO-UHFFFAOYSA-N

物化性质

• 沸点：
  581.8±50.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  胆固醇甲酰氯 、 mitomycin-C 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以83%的产率得到cholesteryloxycarbonyl mitomycin C
  参考文献：
  名称：

  Development of lipophilic prodrugs of mitomycin C. III. Physicochemical and biological properties of newly synthesized alkoxycarbonyl derivatives.

  摘要：

  研究人员合成了五种丝裂霉素 C 的烷氧羰基衍生物，这些衍生物具有不同的亲脂原基，包括苄氧羰基、丙氧羰基、戊氧羰基、壬氧羰基和胆绿羰基，并考察了它们的理化和生物学特性。根据其原分子结构的不同，所有化合物的辛醇/水分配系数、高效液相色谱亲脂指数（k'o）和脂溶性都有不同程度的增加。它们对大肠杆菌 B 仅表现出轻微的抗菌活性，但除胆绿羰基丝裂霉素 C 外，所有化合物在体内对 L1210 白血病系统均表现出相对较低剂量范围内的显著活性。这些衍生物在大鼠血浆和肝匀浆中显示出酶介导的母体化合物转化，而在中性水介质中化学性质稳定。在这些生物活化现象中观察到了物种差异。这些结果表明了这些衍生物作为亲脂性原药的潜在用途。

  DOI：

  10.1248/cpb.31.4083

文献信息

• Liposomal sustained-release delivery systems for intravenous injection. I. Physicochemical and biological properties of newly synthesized lipophilic derivatives of mitomycin C.
  作者：YUJI TOKUNAGA、TOMOAKI IWASA、JIRO FUJISAKI、SEIJI SAWAI、AKIRA KAGAYAMA

  DOI：10.1248/cpb.36.3060

  日期：——

  1a-N-Stearoyl mitomycin C (MMC) and six 1a-N-substituted derivatives of MMC possessing the cholesteryl moiety with different spacers were synthesized, and their biopharmaceutical properties were studied to assess the feasibility of such derivatives as prodrugs for intravenously injectable liposomal sustained-release carrier systems. All compounds showed increased lipophilic indices (logk'0) in high performance liquid chromatography. It was found that all the derivatives could be almost completely entrapped in liposomes, although MMC itself was hardly encapsulated. The derivatives with the exception of cholesteryloxycarbonyl MMC (II) and N-(cholesteryloxy-carbonyl)-4-aminophenylacetyl MMC (VI) were converted to the parent drug in rat serum. The suceptibility of the compounds to hydrolysis was strongly affected by the spacer structure between MMC and the cholesteryl moiety. Cholesteryloxyacetyl MMC (IV) was converted to MMC mainly by chemical hydrolysis. N-(Cholesteryloxycarbonyl)glycyl MMC (III) was also hydrolyzed to MMC chemically but in this case hydrolysis was accelerated in the presence of mouse, rat and human serum. No species differences were observed in these bioactivation phenomena. Entrapment of derivatives III and IV in liposomes resulted in enhancement of the stability against both chemical and enzymatic hydrolysis. The derivatives possessing the cholesteryl moiety were firmly associated with liposomes in the circulation, while stearoyl MMC (VIII) was rapidly recoved. These results suggest that derivatives III and IV have the potential to be utilized as lipophilic prodrugs for liposomal sustained-release carrier systems to be delivered by intravenous injection.

  1a-N-硬脂酰基丝裂霉素C（MMC）及其六种具有胆固醇基团的MMC衍生替代品（含不同的间隔基）被合成，并研究了它们的药物特性，以评估这些衍生物作为静脉注射脂质体长效释放载体系统的药物前体的可行性。所有化合物在高效液相色谱中显示出增加的脂溶性指数（logk'0）。发现所有衍生物几乎可以完全被包裹在脂质体中，尽管MMC本身很难被包裹。除了胆固醇氧甲酰MMC（II）和N-（胆固醇氧甲酰基）-4-氨基苯乙酰基MMC（VI）之外，所有其他衍生物在鼠血清中转化为其母体药物。这些化合物对水解作用的影响受到了MMC和胆固醇基团之间间隔基结构的强烈影响。胆固醇氧乙酰基MMC（IV）主要由化学水解转化为MMC。N-（胆固醇氧甲酰基）甘氨酰MMC（III）也被化学水解为MMC，但在这种情况下，在小鼠、大鼠和人类血清中的水解作用被加速。在这些生物活化现象中没有观察到物种差异。将III和IV衍生物包裹在脂质体中，增强了其抵御化学和酶水解的稳定性。具有胆固醇基团的衍生物在循环中与脂质体紧密结合，而硬脂酰MMC（VIII）则迅速恢复。这些结果表明，III和IV衍生物有可能作为脂质体长效释放载体系统的脂溶性药物前体，通过静脉注射进行输送。
• Verfahren zur Reklonierung von Produktionszellen
  申请人：Boehringer Ingelheim Pharma GmbH & Co. KG

  公开号：EP1918364A2

  公开（公告）日：2008-05-07

  Neues Verfahren zur Klonselektion und Reklonierung von Säugerzellen, die für die Produktion von Biopharmazeutika von Bedeutung sind, vorzugsweise von Hamster- oder Maus-Myeloma-Zellen, mit hohem Automatisierungsgrad und Durchsatz. Die Erfindung betrifft Verfahren zur Ablage und Vermehrung von Einzellzellklonen der entsprechenden Zellen. Ferner betrifft die Erfindung Verfahren zur Herstellung von Proteinen unter Verwendung von Zellen, die mittels Einzelzellablage gewonnen und vermehrt wurden sowie Zusammensetzungen, die eine Vermehrung von Einzelzellen ermöglichen.

  用于克隆选择和重克隆对生物制药生产具有重要意义的哺乳动物细胞（最好是仓鼠或小鼠骨髓瘤细胞）的新方法，自动化程度高，产量大。本发明涉及相应细胞的单细胞克隆的沉积和繁殖方法。此外，本发明还涉及使用通过单细胞沉积获得和繁殖的细胞生产蛋白质的方法，以及能够繁殖单细胞的组合物。
• Combination therapies for bladder cancer
  申请人：GENEDIA BIOTECH CO. LTD.

  公开号：US10238688B2

  公开（公告）日：2019-03-26

  The disclosure provides drug combinations and methods for treating human bladder cancer. The drug combination may include mitomycin, or an analog thereof, cisplatin or an alternative platinum drug, and epirubicin or an alternative anthracycline drug and does not include gemcitabine.

  本公开提供了治疗人类膀胱癌的药物组合和方法。药物组合可包括丝裂霉素或其类似物、顺铂或替代铂类药物、表柔比星或替代蒽环类药物，但不包括吉西他滨。
• Method for recloning production cells
  申请人：Otto Ralf

  公开号：US20050059146A1

  公开（公告）日：2005-03-17

  A new method for selecting clones and recloning mammalian cells which are of importance for the production of biopharmaceuticals, preferably hamster or mouse myeloma cells, with a high degree of automation and throughput. The invention relates to methods of depositing and replicating single cell clones of the cells in question. The invention also relates to methods of preparing proteins using cells which have been obtained and replicated by single cell deposition as well as compositions which allow the replication of single cells.

  一种新方法，用于选择克隆和重克隆对生产生物制药具有重要意义的哺乳动物细胞，最好是仓鼠或小鼠骨髓瘤细胞，自动化程度高，产量大。本发明涉及沉积和复制有关细胞的单细胞克隆的方法。本发明还涉及使用通过单细胞沉积获得和复制的细胞制备蛋白质的方法，以及可以复制单细胞的组合物。
• Efficient mitomycin C coupling with stable p-nitrophenyl-benzyl carbonates using n-hydroxybenzotriazole as a catalytic additive
  作者：Gene M. Dubowchik、H. Dalton King、Kahnie Pham-Kaplita

  DOI：10.1016/s0040-4039(97)01159-3

  日期：1997.7

  Mitomycin C benzyl carbamates were prepared in high yield from stable p-nitrophenyl carbonates in the presence of catalytic amounts of 1-hydroxybenzotriazole/diisopropylethylamine in DMF. (C) 1997 Elsevier Science Ltd.