7-(N-piperidino)mitomycin | 4154-16-9

• 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: 7-(N-piperidino)mitomycin
• 英文别名: 6-(N-Piperidino)mitomycin C；[(4S,6S,7R,8S)-7-methoxy-12-methyl-10,13-dioxo-11-piperidin-1-yl-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
• CAS: 4154-16-9
• 化学式: C₂₀H₂₆N₄O₅
• 分子量: 402.45
• InChiKey: ORLOZWNXWWYWCA-PTTPRXRQSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  619.2±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-(N-piperidino)mitomycin 在 platinum(IV) oxide 2-[Bis(2-hydroxyethyl)imino]-2-(hydroxymethyl)-1,3-propanediol Hydrochloride 、 氢气 作用下， 生成 2-amino-10-decarbamoyl-7-(N-piperidino)mitosene 、 2-amino-7-(N-piperidino)mitosene 、 trans-2-amino-10-decarbamoyl-1-hydroxy-7-(N-piperidino)mitosene 、 cis-2-amino-10-decarbamoyl-1-hydroxy-7-(N-piperidino)mitosene
  参考文献：
  名称：

  Comparative reactivities of mitomycin C, 7-(N-piperidino)mitomycin, and mitomycin A. The role of the C(7) substituent

  摘要：

  Mitomycin C (1a) is considered to be the protypical bioreductive alkylating agent. Enzymatic reduction leads to activation of the two DNA-bonding sites (C(1) and C(10) in 1a, permitting the formation of intrahelical interstrand DNA-mitomycin C cross-link adducts. Drug discovery programs have uncovered several C(7) mitomycin analogues that display a superior profile versus 1a when assayed against a battery of tumor models. The chemical properties of these and related C(7)-substituted mitomycins have not been extensively explored. We have compared the reactivity of mitomycin C (1a) with the two C(7)-substituted mitomycins, 7-(N-piperidino)mitomycin (1b) and mitomycin A (1c), under reductive conditions in tetrahydrofuran-water mixtures (''pH'' 5.5, 6.5). Key observations included (1) enhanced levels of drug utilization in proceeding from 1a to 1b and 1c, (2) increased percentages in the activation of the C(1) and C(10) bonding sites in 1b, c versus 1a, and (3) increased amounts of C(1) nucleophilic and C(10) nucleophilic products for 1b, c versus 1a. The results of these findings are discussed in light of previous studies, the role of the C(7) substituent in the mode of mitomycin action, and the design of future mitomycin analogues.

  DOI：

  10.1021/ja00076a008
• 作为产物：
  描述：

  丝裂霉素 C 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 60.0h， 生成 7-(N-piperidino)mitomycin
  参考文献：
  名称：

  Comparative reactivities of mitomycin C, 7-(N-piperidino)mitomycin, and mitomycin A. The role of the C(7) substituent

  摘要：

  Mitomycin C (1a) is considered to be the protypical bioreductive alkylating agent. Enzymatic reduction leads to activation of the two DNA-bonding sites (C(1) and C(10) in 1a, permitting the formation of intrahelical interstrand DNA-mitomycin C cross-link adducts. Drug discovery programs have uncovered several C(7) mitomycin analogues that display a superior profile versus 1a when assayed against a battery of tumor models. The chemical properties of these and related C(7)-substituted mitomycins have not been extensively explored. We have compared the reactivity of mitomycin C (1a) with the two C(7)-substituted mitomycins, 7-(N-piperidino)mitomycin (1b) and mitomycin A (1c), under reductive conditions in tetrahydrofuran-water mixtures (''pH'' 5.5, 6.5). Key observations included (1) enhanced levels of drug utilization in proceeding from 1a to 1b and 1c, (2) increased percentages in the activation of the C(1) and C(10) bonding sites in 1b, c versus 1a, and (3) increased amounts of C(1) nucleophilic and C(10) nucleophilic products for 1b, c versus 1a. The results of these findings are discussed in light of previous studies, the role of the C(7) substituent in the mode of mitomycin action, and the design of future mitomycin analogues.

  DOI：

  10.1021/ja00076a008

文献信息

• Comparative reactivities of mitomycin C, 7-(N-piperidino)mitomycin, and mitomycin A. The role of the C(7) substituent
  作者：Suganthini Subramaniam、Harold Kohn

  DOI：10.1021/ja00076a008

  日期：1993.11

  Mitomycin C (1a) is considered to be the protypical bioreductive alkylating agent. Enzymatic reduction leads to activation of the two DNA-bonding sites (C(1) and C(10) in 1a, permitting the formation of intrahelical interstrand DNA-mitomycin C cross-link adducts. Drug discovery programs have uncovered several C(7) mitomycin analogues that display a superior profile versus 1a when assayed against a battery of tumor models. The chemical properties of these and related C(7)-substituted mitomycins have not been extensively explored. We have compared the reactivity of mitomycin C (1a) with the two C(7)-substituted mitomycins, 7-(N-piperidino)mitomycin (1b) and mitomycin A (1c), under reductive conditions in tetrahydrofuran-water mixtures (''pH'' 5.5, 6.5). Key observations included (1) enhanced levels of drug utilization in proceeding from 1a to 1b and 1c, (2) increased percentages in the activation of the C(1) and C(10) bonding sites in 1b, c versus 1a, and (3) increased amounts of C(1) nucleophilic and C(10) nucleophilic products for 1b, c versus 1a. The results of these findings are discussed in light of previous studies, the role of the C(7) substituent in the mode of mitomycin action, and the design of future mitomycin analogues.