dimethyl <1-(4-methoxyphenyl)-2-<2-nitro-6-(trifluoromethyl)phenyl>ethyl>propanedioate | 111604-99-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: dimethyl <1-(4-methoxyphenyl)-2-<2-nitro-6-(trifluoromethyl)phenyl>ethyl>propanedioate
• 英文别名: [1-(4-Methoxyphenyl)-2-[2-nitro-6-(trifluoromethyl)phenyl]ethyl]propanedioic acid,dimethyl ester；[2-(2-Nitro-6-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethyl ester；[2-(6-Trifluoromethyl-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester；[1-(4-Methoxyphenyl)-2-[2-nitro-6-(trifluoromethyl)phenyl]ethyl]propanedioic acid, dimethyl ester；dimethyl 2-[1-(4-methoxyphenyl)-2-[2-nitro-6-(trifluoromethyl)phenyl]ethyl]propanedioate
• CAS: 111604-99-0
• 化学式: C₂₁H₂₀F₃NO₇
• 分子量: 455.388
• InChiKey: NOPMPHDCUCMROO-UHFFFAOYSA-N

物化性质

• 熔点：
  117-119 °C
• 沸点：
  498.4±45.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  dimethyl <1-(4-methoxyphenyl)-2-<2-nitro-6-(trifluoromethyl)phenyl>ethyl>propanedioate 在 palladium on activated charcoal Rh/Al₂O₃ 、 氨 、 氢气 、 sodium methylate 、 sodium hydride 、 lithium bromide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 45.0 ℃ 、344.73 kPa 条件下， 反应 37.42h， 生成 (3S,4S)-1-(1-aminopropan-2-yl)-4-(4-methoxyphenyl)-3-methyl-6-(trifluoromethyl)-4,5-dihydro-3H-1-benzazepin-2-one
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site

  摘要：

  We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presence of two pharmacophores: a 4'-aryl methyl ether and a basic substituent appended to N1 with a pK(a) in the physiological range. When these constraints are satisfied, a wide variety of substitution is tolerated at C6, C7, and C3. The presence of an electron-withdrawing group at C6 appears to enhance potency in vitro and in vivo. For such benzazepinones, activity is primarily dependent upon lipophilicity, as measured by log P. We believe these compounds must partition into the cell membrane in order to access their receptor. The quaternary methiodide 15k was used to demonstrate that the binding site for benzazepinones is on the intracellular face of the membrane. This work represents the first comprehensive SAR of diltiazem-like calcium channel blockers.

  DOI：

  10.1021/jm00082a020
• 作为产物：
  描述：

  4-甲氧基苯亚甲基丙二酸二甲酯 生成 dimethyl <1-(4-methoxyphenyl)-2-<2-nitro-6-(trifluoromethyl)phenyl>ethyl>propanedioate
  参考文献：
  名称：

  ATWAL, KARNAIL

  摘要：

  DOI：

文献信息

• Benzazepine derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04748239A1

  公开（公告）日：1988-05-31

  Vasodilating activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof.

  扩血管活性由具有以下结构式的化合物和其药用可接受的盐所表现。
• Process for benzazepine intermediates
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05053504A1

  公开（公告）日：1991-10-01

  A process is disclosed for providing benzazepine intermediates of the formulae ##STR1## wherein R.sub.3, R.sub.4 and Y are as defined herein, which intermediates are useful in a process for the preparation of pharmaceutically useful benzazepine derivatives.

  揭示了一种用于提供苯并哌啶中间体的方法，其化学式为##STR1## 其中R.sub.3、R.sub.4和Y如本文所定义，这些中间体在制备药用苯并哌啶衍生物的过程中是有用的。
• Benzazepinone calcium channel blockers. 2. Structure activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones
  作者：David M. Floyd、S. David Kimball、John Krapcho、Jagabandhu Das、Chester F. Turk、Robert V. Moquin、Michael W. Lago、Keith J. Duff、Ving G. Lee

  DOI：10.1021/jm00082a018

  日期：1992.2

  discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies

  作为发现地尔硫卓有效降压类似物的程序的一部分，我们制备了1-benzazepin-2-ones（4）。苯并ze庚因酮竞争性地取代了放射性标记的地尔硫卓，并在钙通道受体蛋白上表现出相同的绝对立体化学偏好。在稠合的芳族环中含有三氟甲基取代基的4的衍生物表现出有效的长效降压活性。对4的代谢的研究导致了代谢稳定的降压钙通道阻滞剂5a和5c。与第二代地尔硫卓类似物TA-3090（3e）相比，苯并ze庚酮5a是更长效且更有效的降压药。
• Das, Jagabandhu; Floyd, David M; Kimball, S David, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 12, p. 817 - 820
  作者：Das, Jagabandhu、Floyd, David M、Kimball, S David、Patel, Ramesh N、Thottathil, John K

  DOI：——

  日期：——
• Fluoride-catalyzed Michael addition of nitrotoluenes to activated α, β-unsaturated esters
  作者：Wen-Sen Li、John Thottathil、Michael Murphy

  DOI：10.1016/s0040-4039(00)73443-5

  日期：1994.9

  We have found that in the presence of fluoride ion, nitrotoluenes of type 1 undergo Michael addition to activated alpha, beta-unsaturated esters of type 2 in good to excellent yield (Scheme 1). The generality and limitation of this reaction and its application to the chiral synthesis of benzazepine 4 are described.