Dannhardt G, Dominiak P, Laufer S
Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Frankfurt/Main Fed. Rep. of Germany.
Arzneimittelforschung. 1993 Apr;43(4):441-4.
Structure-activity and dose-response relationships of a series of novel 5-omega aminoalkyl and 5-omega-amino-heteroalkyl isoxazoles on blood pressure and heart rate of Sprague-Dawley rats have been investigated. To differentiate between peripheral and central cardiovascular actions of those compounds a pithed rat and anaesthetized rat preparation was used. Most of the compounds investigated exhibit potent hypertensive actions. The hypertensive effects of the tested compounds is depending on the amphiphilic character of the isoxazoles represented by a basic moiety in a definite distance to the phenyl substituents. To achieve high pharmacological activity a fully flexible side chain is requested, too. Possible mechanisms of action are discussed.
研究了一系列新型5-ω-氨基烷基和5-ω-氨基杂烷基异恶唑对Sprague-Dawley大鼠血压和心率的构效关系及剂量反应关系。为区分这些化合物的外周和中枢心血管作用，使用了脊髓切断大鼠和麻醉大鼠模型。所研究的大多数化合物表现出强效的升压作用。受试化合物的升压作用取决于异恶唑的两亲性特征，该特征由与苯基取代基有一定距离的碱性部分表示。为获得高药理活性，还需要一个完全灵活的侧链。文中讨论了可能的作用机制。
