ethyl (2R)-2-[[3-(nitrooxymethyl)benzoyl]amino]-3-sulfanylpropanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (2R)-2-[[3-(nitrooxymethyl)benzoyl]amino]-3-sulfanylpropanoate
• 化学式: C₁₃H₁₆N₂O₆S
• 分子量: 328.346
• InChiKey: BNOVIFMNVKELTH-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  L-半胱氨酸乙酯盐酸盐 、 3-((nitrooxy)methyl)benzoyl chloride 在 sodium acetate 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 ethyl (2R)-2-[[3-(nitrooxymethyl)benzoyl]amino]-3-sulfanylpropanoate
  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.