乙基(2R)-2-[(2,2-二甲基-3-硝基氧基丙酰)氨基]-3-巯基丙酸酯 | 130432-17-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 乙基(2R)-2-[(2,2-二甲基-3-硝基氧基丙酰)氨基]-3-巯基丙酸酯
• 英文名称: SPM 3672
• 英文别名: SPM-3672；N-3-nitrooxy-2,2-dimethylpropanoyl-L-cysteine ethyl ester；SPM3672；N-(3-Nitratopivaloyl)cysteine ethyl ester；ethyl (2R)-2-[(2,2-dimethyl-3-nitrooxypropanoyl)amino]-3-sulfanylpropanoate
• CAS: 130432-17-6
• 化学式: C₁₀H₁₈N₂O₆S
• 分子量: 294.329
• InChiKey: KCKXBNDUEKMBFJ-ZETCQYMHSA-N

物化性质

• 沸点：
  443.3±45.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  萘普生 、 乙基(2R)-2-[(2,2-二甲基-3-硝基氧基丙酰)氨基]-3-巯基丙酸酯 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以7.6%的产率得到N-3-nitrooxy-2,2-dimethylpropanoyl-S-(+)-2-(6-methoxy-2-naphthyl)propanoyl-L-cysteine ethyl ester
  参考文献：
  名称：

  NO-Donors (VII [1]): Synthesis and Cyclooxygenase Inhibitory Properties of N-and S-Nitrooxypivaloyl-cysteine Derivatives of Naproxen — A Novel Type of NO-NSAID

  摘要：

  Nitric oxide (NO) has been reported to subserve many of the same mucosal protection mechanisms as prostaglandins and is sufficient for acute gastroprotection and ulcer healing. In fact, NO-donating NSAID hybrid compounds such as the nitrooxybutyl ester of naproxen show reduced ulcerogenic activity while maintaining anti-inflammatory activity. We introduce two prototypes of novel triple-hybrid compounds consisting of cysteine which is known to enhance the activity of organic nitrates and to reduce nitrate tolerance, an NSAID (naproxen), and an organic nitrate (nitrooxypivaloic acid). L-Cysteine ethyl ester first was N-acylated in a CH2Cl2/H2O two-phase system using the acid chlorides of naproxen or nitrooxypivaloic acid, respectively, and sodium acetate, or alternatively using the DCC-activated nitrooxy acid in absolute CH2Cl2. The N-acylated intermediates were subsequently S-acylated using the acid chlorides or alternatively the carbonyldiimidazole (CDI)-activated acids again. The two naproxon-cysteine-nitrate hybrid prodrugs were screened in vitro for their cyclooxygenase inhibitory properties relative to naproxen. In this screening the N-nitrooxyacylcysteine derivative was found to be inactive in the concentration range of 0.1-10 mumol/L against both COX-1 and COX-2, while the S-nitrooxyacylcysteine derivative had only weak activity against COX-1.

  DOI：

  10.1002/1521-4184(200211)335:8<363::aid-ardp363>3.0.co;2-s
• 作为产物：
  描述：

  2,2-二甲基-3-(硝基氧基)丙酸 在 氯化亚砜 、 sodium acetate 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 1.5h， 生成 乙基(2R)-2-[(2,2-二甲基-3-硝基氧基丙酰)氨基]-3-巯基丙酸酯
  参考文献：
  名称：

  NO-Donors (VII [1]): Synthesis and Cyclooxygenase Inhibitory Properties of N-and S-Nitrooxypivaloyl-cysteine Derivatives of Naproxen — A Novel Type of NO-NSAID

  摘要：

  Nitric oxide (NO) has been reported to subserve many of the same mucosal protection mechanisms as prostaglandins and is sufficient for acute gastroprotection and ulcer healing. In fact, NO-donating NSAID hybrid compounds such as the nitrooxybutyl ester of naproxen show reduced ulcerogenic activity while maintaining anti-inflammatory activity. We introduce two prototypes of novel triple-hybrid compounds consisting of cysteine which is known to enhance the activity of organic nitrates and to reduce nitrate tolerance, an NSAID (naproxen), and an organic nitrate (nitrooxypivaloic acid). L-Cysteine ethyl ester first was N-acylated in a CH2Cl2/H2O two-phase system using the acid chlorides of naproxen or nitrooxypivaloic acid, respectively, and sodium acetate, or alternatively using the DCC-activated nitrooxy acid in absolute CH2Cl2. The N-acylated intermediates were subsequently S-acylated using the acid chlorides or alternatively the carbonyldiimidazole (CDI)-activated acids again. The two naproxon-cysteine-nitrate hybrid prodrugs were screened in vitro for their cyclooxygenase inhibitory properties relative to naproxen. In this screening the N-nitrooxyacylcysteine derivative was found to be inactive in the concentration range of 0.1-10 mumol/L against both COX-1 and COX-2, while the S-nitrooxyacylcysteine derivative had only weak activity against COX-1.

  DOI：

  10.1002/1521-4184(200211)335:8<363::aid-ardp363>3.0.co;2-s

文献信息

• NO-Donors (VII [1]): Synthesis and Cyclooxygenase Inhibitory Properties of N-and S-Nitrooxypivaloyl-cysteine Derivatives of Naproxen — A Novel Type of NO-NSAID
  作者：Rahmana E. Kartasasmita、Stefan Laufer、Jochen Lehmann

  DOI：10.1002/1521-4184(200211)335:8<363::aid-ardp363>3.0.co;2-s

  日期：2002.11

  Nitric oxide (NO) has been reported to subserve many of the same mucosal protection mechanisms as prostaglandins and is sufficient for acute gastroprotection and ulcer healing. In fact, NO-donating NSAID hybrid compounds such as the nitrooxybutyl ester of naproxen show reduced ulcerogenic activity while maintaining anti-inflammatory activity. We introduce two prototypes of novel triple-hybrid compounds consisting of cysteine which is known to enhance the activity of organic nitrates and to reduce nitrate tolerance, an NSAID (naproxen), and an organic nitrate (nitrooxypivaloic acid). L-Cysteine ethyl ester first was N-acylated in a CH2Cl2/H2O two-phase system using the acid chlorides of naproxen or nitrooxypivaloic acid, respectively, and sodium acetate, or alternatively using the DCC-activated nitrooxy acid in absolute CH2Cl2. The N-acylated intermediates were subsequently S-acylated using the acid chlorides or alternatively the carbonyldiimidazole (CDI)-activated acids again. The two naproxon-cysteine-nitrate hybrid prodrugs were screened in vitro for their cyclooxygenase inhibitory properties relative to naproxen. In this screening the N-nitrooxyacylcysteine derivative was found to be inactive in the concentration range of 0.1-10 mumol/L against both COX-1 and COX-2, while the S-nitrooxyacylcysteine derivative had only weak activity against COX-1.