(1S,2R)-2-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-1-methylethyl acetoacetate | 128108-06-5

• 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: (1S,2R)-2-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-1-methylethyl acetoacetate
• 英文别名: methyl (2R,3S)-2-[(3,5-dinitrobenzoyl)amino]-3-(3-oxobutanoyloxy)butanoate
• CAS: 128108-06-5
• 化学式: C₁₆H₁₇N₃O₁₀
• 分子量: 411.325
• InChiKey: ZYHPSZKJTDAURE-LKFCYVNXSA-N

物化性质

• 熔点：
  79-80 °C
• 沸点：
  531.5±50.0 °C(predicted)
• 密度：
  1.416±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  190
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (1S,2R)-2-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-1-methylethyl acetoacetate 在 氨 、 对甲苯磺酸 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 22.0h， 生成 (1S,2R)-2-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-1-methylethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate
  参考文献：
  名称：

  Syntheses, Calcium Channel Agonist−Antagonist Modulation Activities, Nitric Oxide Release, and Voltage-Clamp Studies of 2-Nitrooxyethyl 1,4-Dihydro- 2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate Enantiomers

  摘要：

  The novel (-)-(S)-2 and (+)-(R)-3 enantiomers of 2-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate were synthesized for evaluation as calcium channel modulators. Determination of their in vitro calcium-channel-modulating activities using guinea pig left atria (GPLA) and ileum longitudinal smooth muscle (GPILSM) showed that the (-)-(S)-2 enantiomer acted as a dual cardioselective calcium channel agonist (GPLA)/smooth muscle selective calcium channel antagonist (GPILSM). In contrast, the (+)(R)-3 enantiomer exhibited calcium channel antagonist activity on both GPLA and GPILSM. The 2-nitrooxyethyl racemate is a nitric oxide ((NO)-N-.) donor that released 2.7% (NO)-N-., relative to the reference drug glyceryl trinitrate (5.3% (NO)-N-. release/ONO2 moiety), in the presence of N-acetylcysteamine. Whole-cell voltage-clamp studies using isolated guinea pig ventricular myocytes indicated that both enantiomers inhibit calcium current but that the (-)-(S)-2 enantiomer is a weaker antagonist than the (+)-(R)-3 enantiomer. These results indicate that replacement of the methyl ester substituent of (-)-(S)-methyl 1,4-dihydro-2,6-dimetyl-3-nitro4-(2-trifluoromethylphenyl)pyridine-5-carboxylate [(-)-(S)-1] by the 2-nitrooxyethyl ester (NO)-N-. donor substituent present in (-)-(S)-2 provides a useful drug design concept to abolish the contraindicated calcium channel agonist effect of (-)-(S)-1 on vascular smooth muscle. The novel (-)-(S)-2 enantiomer is a useful lead compound for drug discovery targeted toward the treatment of congestive heart failure, and it provides a useful probe to study the structure-function relationships of calcium channels.

  DOI：

  10.1021/jm010394k
• 作为产物：
  描述：

  2,2,6-三甲基-4H-1,3-二英-4-酮 、 methyl (2R,3S)-2-(3,5-dinitrophenylcarbonylamino)-3-hydroxybutanoate 以 xylene 为溶剂， 反应 0.5h， 以94%的产率得到(1S,2R)-2-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-1-methylethyl acetoacetate
  参考文献：
  名称：

  The design of (−)-(S)-2-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)Pyridine-5-carboxylate: A cardioselective positive inotropic derivative of bay K 8644

  摘要：

  The title compound, (-)-(S)-9, is a novel cardioselective calcium channel modulator that exhibits a calcium channel agonist effect on heart, a weak calcium channel antagonist effect on smooth muscle, and releases nitric oxide in vitro. (-)-(S)-9 is a useful lead-compound for the design of positive inotropic agents to treat congestive heart failure, and to study the structure-function relationship of calcium channel modulation. (C) 1999 Elsevier Science Ltd. Ail rights reserved.

  DOI：

  10.1016/s0960-894x(99)00445-x