α-methyl-<2-<2-amino-5-(trifluoromethyl)phenyl>-1-(4-methoxyphenyl)ethyl>propanedioic acid dimethyl ester | 111604-87-6

• 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: α-methyl-<2-<2-amino-5-(trifluoromethyl)phenyl>-1-(4-methoxyphenyl)ethyl>propanedioic acid dimethyl ester
• 英文别名: α-methyl-[2-(2-amino-5-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester；alpha-Methyl-[2-(2-amino-5-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester；dimethyl 2-[2-[2-amino-5-(trifluoromethyl)phenyl]-1-(4-methoxyphenyl)ethyl]-2-methylpropanedioate
• CAS: 111604-87-6
• 化学式: C₂₂H₂₄F₃NO₅
• 分子量: 439.431
• InChiKey: KQUKXTWDWGAKCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  87.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  α-methyl-<2-<2-amino-5-(trifluoromethyl)phenyl>-1-(4-methoxyphenyl)ethyl>propanedioic acid dimethyl ester 在 吡啶 、 sodium methylate 、 sodium hydride 、 lithium iodide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.83h， 生成 cis-1-<2-(dimethylamino)ethyl>-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-3-methyl-7-(trifluoromethyl)-2H-1-benzazepin-2-one
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 3. Synthesis and structure-activity studies of 3-alkylbenzazepinones

  摘要：

  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.

  DOI：

  10.1021/jm00082a019
• 作为产物：
  描述：

  α-methyl-<1-(4-methoxyphenyl)-2-<2-nitro-5-(trifluoromethyl)phenyl>ethyl>propanedioic acid dimethyl ester 在 盐酸 、 tin(ll) chloride 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以95%的产率得到α-methyl-<2-<2-amino-5-(trifluoromethyl)phenyl>-1-(4-methoxyphenyl)ethyl>propanedioic acid dimethyl ester
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 3. Synthesis and structure-activity studies of 3-alkylbenzazepinones

  摘要：

  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.

  DOI：

  10.1021/jm00082a019

文献信息

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

  公开号：US04752645A1

  公开（公告）日：1988-06-21

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

  具有如下式子##STR1##和其药学上可接受的盐，表现出扩张血管的活性。
• 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.