2-(ethylthio)ethyl-2,6-dimethyl-5-ethoxycarbonyl-4-n-propyl-1,4-dihydropyridin-3-carboxylate | 123874-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(ethylthio)ethyl-2,6-dimethyl-5-ethoxycarbonyl-4-n-propyl-1,4-dihydropyridin-3-carboxylate
• 英文别名: 3-O-ethyl 5-O-(2-ethylsulfanylethyl) 2,6-dimethyl-4-propyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 123874-98-6
• 化学式: C₁₈H₂₉NO₄S
• 分子量: 355.499
• InChiKey: TUACHGGIJXCLCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(ethylthio)ethyl-acetylacetate 、 (E)-3-氨基巴豆酸乙酯 、 正丁醛 以 乙醇 为溶剂， 反应 10.0h， 以62%的产率得到2-(ethylthio)ethyl-2,6-dimethyl-5-ethoxycarbonyl-4-n-propyl-1,4-dihydropyridin-3-carboxylate
  参考文献：
  名称：

  4-Alkyl-1,4-dihydropyridine derivatives as specific PAF-acether antagonists

  摘要：

  A new series of 4-alkyl-1,4-dihydropyridines (1,4-DHP) were synthesized and evaluated for their ability to inhibit washed rabbit platelet aggregation induced by PAF-acether (1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) and to reverse PAF-induced hypotension in anesthetized rats. Additionally, compounds were evaluated for their ability to inhibit the binding of radiolabeled PAF to its receptor on rabbit platelets. Among these compounds, 6I and 6L were the most potent and specific antagonists. At concentrations up to 100 microM, neither compound 6I nor compound 6L caused platelet aggregation nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Compound 6L did not show in vitro calcium channel blocker activity measured on vascular smooth muscle preparations of rabbit aorta and on [3H]nitrendipine binding assays. The compound did not show any cardiovascular effects in anesthetized rat at iv doses up to 1000 micrograms/kg, and the Ki value was 568.62 nmol. These results indicate that compound 6L is a potent and specific PAF antagonist with 1,4-dihydropyridine structure but devoid of a significant cardiovascular activity related to calcium-antagonist properties.

  DOI：

  10.1021/jm00174a017

文献信息

• 4-alkyl-1,4-dihydropyridines with PAF-antagonist activity
  申请人：Alter, S.A.

  公开号：US05177211A1

  公开（公告）日：1993-01-05

  4-alkyl-1,4-dihyropyridines, with PAF-antagonist activity, of formula (I) wherein R is saturated C.sub.1 -C.sub.4, R' is saturated C.sub.1 -C.sub.6 alkyl which may be interrupted by an oxygen atom, or 2-tetrahydrofurfuryl and R.sup.2 is saturated C.sub.1 -C.sub.4 or phenyl, the compound wherein R is methyl, R' is ethyl and R.sup.2 is phenyl remain excluded, are described. The compounds (I) are prepared by: (a) reaction of (II) with (III); (b) reaction of (IV) with (V); (c) reaction of (VI) with (III) and with (VII); (d) reaction of (VIII) with (V) and with (VII); or (e) reaction of (VIII) with (VI) and with (VII) in the presence of ammonia. The compounds (I) are useful due to their antagonist activity of the platelet activating factor. ##STR1##

  4-烷基-1,4-二氢吡啶，具有PAF拮抗活性，其化学式为（I），其中R为饱和的C.sub.1-C.sub.4，R'为饱和的C.sub.1-C.sub.6烷基，可以被氧原子中断，或2-四氢呋喃基，R.sup.2为饱和的C.sub.1-C.sub.4或苯基，其中化合物中R为甲基，R'为乙基，R.sup.2为苯基除外。化合物（I）通过以下方法制备：（a）将（II）与（III）反应；（b）将（IV）与（V）反应；（c）将（VI）与（III）和（VII）反应；（d）将（VIII）与（V）和（VII）反应；或（e）将（VIII）与（VI）和（VII）在氨的存在下反应。由于其拮抗血小板活化因子的活性，化合物（I）具有实用价值。
• 4-Alkyl-1,4-dihydropyridine derivatives as specific PAF-acether antagonists
  作者：Carlos E. Sunkel、Miguel Fau de Casa-Juana、Luis Santos、M. Mar Gomez、Mercedes Villarroya、M. Antonia Gonzalez-Morales、Jaime G. Priego、M. Pilar Ortega

  DOI：10.1021/jm00174a017

  日期：1990.12

  A new series of 4-alkyl-1,4-dihydropyridines (1,4-DHP) were synthesized and evaluated for their ability to inhibit washed rabbit platelet aggregation induced by PAF-acether (1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) and to reverse PAF-induced hypotension in anesthetized rats. Additionally, compounds were evaluated for their ability to inhibit the binding of radiolabeled PAF to its receptor on rabbit platelets. Among these compounds, 6I and 6L were the most potent and specific antagonists. At concentrations up to 100 microM, neither compound 6I nor compound 6L caused platelet aggregation nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Compound 6L did not show in vitro calcium channel blocker activity measured on vascular smooth muscle preparations of rabbit aorta and on [3H]nitrendipine binding assays. The compound did not show any cardiovascular effects in anesthetized rat at iv doses up to 1000 micrograms/kg, and the Ki value was 568.62 nmol. These results indicate that compound 6L is a potent and specific PAF antagonist with 1,4-dihydropyridine structure but devoid of a significant cardiovascular activity related to calcium-antagonist properties.