4-ALKYL-1,4-DIHYDROPYRIDINE DERIVATIVES AS SPECIFIC PAF-ACETHER ANTAGONISTS

被引：87

作者：

SUNKEL, CE ^{[1
]}

DECASAJUANA, MF ^{[1
]}

SANTOS, L ^{[1
]}

GOMEZ, MM ^{[1
]}

VILLARROYA, M ^{[1
]}

GONZALEZMORALES, MA ^{[1
]}

PRIEGO, JG ^{[1
]}

ORTEGA, MP ^{[1
]}

机构：

[1] ALTER SA,RES DEPT,MATEO INURRIA 30,E-28036 MADRID,SPAIN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 12期

关键词：

D O I：

10.1021/jm00174a017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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, 61 and 6L were the most potent and specific antagonists. At concentrations up to 100 μM, neither compound 61 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 μg/kg, and the Kivalue 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. © 1990, American Chemical Society. All rights reserved.

引用

页码：3205 / 3210

页数：6

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