[2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethyl ester | 107966-98-3

• 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: [2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethyl ester
• 英文别名: dimethyl <1-(4-methoxyphenyl)-2-(2-nitro-5-chlorophenyl)ethyl>propanedioate；[2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester；[2-(5-Chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethylester；[2-(5-Chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethylester；dimethyl 2-[2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioate
• CAS: 107966-98-3
• 化学式: C₂₀H₂₀ClNO₇
• 分子量: 421.834
• InChiKey: WDXXZULSZJTJBA-UHFFFAOYSA-N

物化性质

• 熔点：
  128.5-130.5 °C
• 沸点：
  531.4±50.0 °C(Predicted)
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethyl ester 在 盐酸 、 水 、 氧气 、 sodium methylate 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 tin(ll) chloride 、 lithium iodide 、 亚磷酸三乙酯 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 12.0h， 生成 (3R,4S-cis)-3-hydroxy-1-<2-(dimethylamino)ethyl>-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-7-chloro-2H-1-benzazepin-2-one
  参考文献：
  名称：

  苯并ze庚酮钙通道阻滞剂。2.结构活性和药物代谢研究导致有效的降压药。与苯并噻嗪酮的比较。

  摘要：

  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。

  DOI：

  10.1021/jm00082a018
• 作为产物：
  描述：

  4-甲氧基苯亚甲基丙二酸二甲酯 生成 [2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid,dimethyl ester
  参考文献：
  名称：

  DAS, JAGABANDHU;FLOYD, DAVID M.

  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。
• 3-substituted benzazepines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04767756A1

  公开（公告）日：1988-08-30

  Benzazepine derivatives useful, for example, as cardiovascular agents, are disclosed. These compounds have the general formula ##STR1## and pharmaceutically acceptable salts thereof.

  本发明揭示了苯并噻唑衍生物，例如作为心血管药物有用。这些化合物具有一般式##STR1##和其药学上可接受的盐。
• Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site
  作者：S. David Kimball、David M. Floyd、Jagabandhu Das、John T. Hunt、John Krapcho、George Rovnyak、Keith J. Duff、Ving G. Lee、Robert V. Moquin

  DOI：10.1021/jm00082a020

  日期：1992.2

  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.
• 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.
• Benzazepinone calcium channel blockers. 3. Synthesis and structure-activity studies of 3-alkylbenzazepinones
  作者：Jagabandhu Das、David M. Floyd、S. David Kimball、Keith J. Duff、Michael W. Lago、Robert V. Moquin、Ving G. Lee、Jack Z. Gougoutas、Vu Chi Truc

  DOI：10.1021/jm00082a019

  日期：1992.2

  As part of a program aimed at identifying novel analogues of diltiazem, we developed several synthetic routes for 3-alkylbenzazepinones, both in racemic and nonracemic form. Structure-activity relationship studies in this series have led to identification of several analogues as potent calcium channel blocking agents, both in vitro and in vivo. Analogues containing a 6-trifluoromethyl substituent (17a and 17b) are the most potent vasorelaxants in vitro. The oral antihypertensive activity of these compounds is comparable to its 3-acetoxy derivative 1 (X = 6-CF3) and 8-chlorodiltiazem (2b). The 3-allyl analogue 17c is a more potent antihypertensive agent than 17a, 17b, or 8-chlorodiltiazem (2b), and has a longer duration of action in vivo.