O²-(acetoxymethyl) 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate | 259686-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: O²-(acetoxymethyl) 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
• 英文别名: (Z)-acetyloxymethoxyimino-oxido-pyrrolidin-1-ylazanium
• CAS: 259686-42-5
• 化学式: C₇H₁₃N₃O₄
• 分子量: 203.198
• InChiKey: CWFADOONXREEFU-NTMALXAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  79.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O²-(acetoxymethyl) 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate 在 porcine liver esterase E⁽¹¹⁾C₃ 、 Tris-Cl buffer 作用下， 以 甲醇 、 水 为溶剂， 生成 5-氟脲嘧啶
  参考文献：
  名称：

  Synthesis and cytotoxicity of 5-fluorouracil/diazeniumdiolate conjugates

  摘要：

  5-Fluorouracil/diazeniumdiolate conjugates were first synthesized, and showed greater cytotoxicities than 5-fluorouracil for DU 145 human prostate and HeLa cancer cells. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.003
• 作为产物：
  描述：

  O²-methylthiomethyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate 在 磺酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 O²-(acetoxymethyl) 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Synthesis and cytotoxicity of 5-fluorouracil/diazeniumdiolate conjugates

  摘要：

  5-Fluorouracil/diazeniumdiolate conjugates were first synthesized, and showed greater cytotoxicities than 5-fluorouracil for DU 145 human prostate and HeLa cancer cells. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.003

文献信息

• Esterase-Sensitive Nitric Oxide Donors of the Diazeniumdiolate Family:  In Vitro Antileukemic Activity
  作者：Joseph E. Saavedra、Paul J. Shami、Lai Yi Wang、Keith M. Davies、Melissa N. Booth、Michael L. Citro、Larry K. Keefer

  DOI：10.1021/jm9903850

  日期：2000.1.1

  We have designed a novel prodrug class that is stable in neutral aqueous media but releases bioactive nitric oxide (NO) on metabolism by esterase. Diazeniumdiolates of structure R2N-N(O)=N-OR', in which R' = Na, were reacted with BrCH2OAc to convert the spontaneously NO-releasing salts 1a (R2N = diethylamino) and 1b (R2N = pyrrolidino) to prodrugs 2a (AcOM-DEA/NO) and 2b (AcOM-PYRRO/NO), respectively, where R' = CH2OAc. In contrast to anions la and Ib (half-lives in pH 7.4 phosphate at 37 degrees C of 2 min and 3 s, respectively), 2a and 2b showed only minimal decomposition after 16 h under these conditions. Very rapid hydrolysis occurred in the presence of porcine liver esterase, however, with free anion 1a being observed as an intermediate in the esterase-induced generation of NO from 2a. The potential utility of this prodrug class is illustrated with a comparison of 1 and 2 as antiproliferative agents in NO-sensitive human leukemia cell lines HL-60 and U937. While the 72-h IC50's for 1a and 1b (which generate NO throughout the medium) in HL-60 cell cultures were >600 mu M, those of 2a and 2b were 8.3 and 6.4 mu M, respectively. This result is consistent with our hypothesis that 2 is selectively hydrolyzed to 1 and thence to NO intracellularly. For U937 cells, the 72-h IC50 for both 2a and 2b was 53 mu M. By contrast, relatively high antiproliferative IC50's (>100 mu M in U937 cells) were observed for analogues in which R' = CH2CH2SC(O)Me, from which acetyl and 2-mercaptoethyl groups must be successively cleaved to free the NO-releasing diazeniumdiolate function. Within 24 h at initial concentrations of 50 mu M, 2a and 2b induced apoptosis in 50% and 57% of the HL-60 cells, respectively (35% and 40% of the U937 cells, respectively). The data reveal significant in vitro antileukemic activity on the part of these novel compounds. Moreover, their substantial ease-of-handling advantages over the anionic diazeniumdiolates from which they are derived suggest their use as convenient agents for probing the biological roles of NO.
• Synthesis and cytotoxicity of 5-fluorouracil/diazeniumdiolate conjugates
  作者：Tingwei Bill Cai、Xiaoping Tang、Janet Nagorski、Paul G Brauschweiger、Peng George Wang

  DOI：10.1016/j.bmc.2003.09.003

  日期：2003.11

  5-Fluorouracil/diazeniumdiolate conjugates were first synthesized, and showed greater cytotoxicities than 5-fluorouracil for DU 145 human prostate and HeLa cancer cells. (C) 2003 Elsevier Ltd. All rights reserved.