Ethyl 5-(2-chlorophenyl)-3,5-dioxopentanoate | 114957-83-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethyl 5-(2-chlorophenyl)-3,5-dioxopentanoate
• CAS: 114957-83-4
• 化学式: C₁₃H₁₃ClO₄
• 分子量: 268.697
• InChiKey: ASZXAVWULNVSGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  邻三氟甲基苯甲醛 、 (E)-3-氨基巴豆酸乙酯 、 Ethyl 5-(2-chlorophenyl)-3,5-dioxopentanoate 以 乙醇 为溶剂， 反应 18.0h， 以4%的产率得到diethyl (2Z,3S,4R)-2-[2-(2-chlorophenyl)-2-oxoethylidene]-6-methyl-4-[2-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-3,5-dicarboxylate
  参考文献：
  名称：

  2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers

  摘要：

  The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.

  DOI：

  10.1021/jm00403a030

文献信息

• Process for the production of 2-chloro-4-substituted-5-thiazolecarboxylates
  申请人：MONSANTO COMPANY

  公开号：EP0027018B1

  公开（公告）日：1983-10-05
• US4308391A
  申请人：——

  公开号：US4308391A

  公开（公告）日：1981-12-29
• US4336389A
  申请人：——

  公开号：US4336389A

  公开（公告）日：1982-06-22
• 2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihydropyridine calcium channel blockers
  作者：Michael D. Taylor、Edward W. Badger、Robert P. Steffen、Stephen J. Haleen、Thomas A. Pugsley、Yu Hsin Shih、Ronald E. Weishaar

  DOI：10.1021/jm00403a030

  日期：1988.8

  The title compounds are novel double bond isomers of 1,4-dihydropyridine-type calcium channel blockers (CCB). These derivatives were prepared by using the Hantzsch dihydropyridine synthesis. The assignment of structure was based on spectroscopic data and a regiochemically unambiguous synthesis. Several of the analogues inhibited [3H]nitrendipine binding with IC50 values as low as 25 nM. By comparison, nifedipine, a clinically useful 1,4-dihydropyridine CCB, inhibits [3H]nitrendipine binding with an IC50 of 1.6 nM. In the Langendorff rat heart preparation, treatment with the more potent derivatives produced marked dose-related increases in coronary flow with little or no effect on heart rate or contractility, except at the highest concentrations tested. The selectivity for vascular versus cardiac effects was similar to that of nifedipine, i.e., the concentration producing vasodilation was approximately 2 orders of magnitude lower than the concentration eliciting cardiodepression. These novel isomers extend the structure-activity relationships for calcium channel blockers into a series closely related to the 1,4-dihydropyridines.