methyl (2R,3S)-2-(3,5-dinitrophenylcarbonylamino)-3-hydroxybutanoate | 135088-97-0

• 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: methyl (2R,3S)-2-(3,5-dinitrophenylcarbonylamino)-3-hydroxybutanoate
• 英文别名: methyl (2R,3S)-2-[(3,5-dinitrobenzoyl)amino]-3-hydroxybutanoate
• CAS: 135088-97-0
• 化学式: C₁₂H₁₃N₃O₈
• 分子量: 327.251
• InChiKey: KLEYMKBMFQAQFJ-QUBYGPBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (2R,3S)-2-(3,5-dinitrophenylcarbonylamino)-3-hydroxybutanoate 在 氨 、 对甲苯磺酸 作用下， 以 乙醇 、 甲苯 、 xylene 为溶剂， 反应 21.5h， 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：

  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
• 作为产物：
  描述：

  D-苏氨酸甲酯盐酸盐 、 3,5-二硝基苯甲酰氯 在 potassium carbonate 作用下， 以 乙酸乙酯 为溶剂， 反应 17.0h， 以84%的产率得到methyl (2R,3S)-2-(3,5-dinitrophenylcarbonylamino)-3-hydroxybutanoate
  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

文献信息

• Clay Column Chromatography for Optical Resolution: A Series of Derivatized Amino Acids
  作者：Akihiko Yamagishi、Shohei Yamamoto、Kazuyoshi Takimoto、Kenji Tamura、Masumi Kamon、Fumi Sato、Hisako Sato

  DOI：10.1246/bcsj.20220077

  日期：2022.6.15

  Chromatographic resolution of a series of derivatized amino acids was attempted on a column packed with an ion-exchange adduct of Δ-[Ru(phen)3]2+ (phen = 1,10-phenanthroline) and synthetic hectorite. An amino acid was modified to N-3, 5-dinitrobenzoyl amino acid methyl ester (denoted by DNB-aa-me). For aa = Ala, Phe, Leu, Ile, Ser, Val, Thr, Tyr, Asp and Glu, racemic DNB-aa-me was resolved nearly to

  在填充有 Δ-[Ru(phen) 3 ] 2+ (phen = 1,10-phenanthroline) 和合成锂蒙脱石的离子交换加合物的色谱柱上尝试了一系列衍生氨基酸的色谱分离。将氨基酸修饰为N -3, 5-二硝基苯甲酰基氨基酸甲酯（记作DNB-aa-me）。对于 aa = Ala、Phe、Leu、Ile、Ser、Val、Thr、Tyr、Asp 和 Glu，在用甲醇洗脱时，外消旋 DNB-aa-me 几乎被分离到基线分离。对于 aa = Trp 和 His，外消旋 DNB-aa-me 部分分离。Pro 和 Lys 没有达到分辨率。通过固态振动圆二色光谱研究了手性鉴别的机理。
• 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
  作者：Rudong Shan、Edward E. Knaus

  DOI：10.1016/s0960-894x(99)00445-x

  日期：1999.9

  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.
• 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
  作者：Rudong Shan、Susan E. Howlett、Edward E. Knaus

  DOI：10.1021/jm010394k

  日期：2002.2.1

  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.