Studies on agents with mixed NO-dependent vasodilating and β-blocking activities

被引:33
作者
Boschi, D [1 ]
Di Stilo, A [1 ]
Cena, C [1 ]
Lolli, M [1 ]
Fruttero, R [1 ]
Gasco, A [1 ]
机构
[1] Dipartimento Sci & Tecnol Farm, I-10125 Turin, Italy
关键词
NO-donors; beta-blockers; hybrid drugs; furoxans; vasodilation;
D O I
10.1023/A:1012136030849
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. A series of derivatives having a propranolol-like moiety linked to NO-donor furoxan substructures were synthesized. The main objective of this investigation was to obtain agents with mixed No-dependent vasodilating and beta-blocking activities. Methods. Most of the target compounds were synthesized from the appropriate furoxans bearing XCH2CH2NH2 (X = O, S, SO2) chains at the 4 position of the ring, using AI(C2H5)(3) in methylene chloride solution and (+/-)2,3-epoxypropyl 1-naphtyl ether. Two of the final products (X = CONH) were obtained by coupling the appropriate furoxancarboxylic acids with N-[2-hydroxy-3-(1-naphthoxy)propyl]ethylenediamine. beta(1)- and beta(2)-blocking activities were examined on isolated guinea pig right atria and on guinea pig trachea respectively. Vasodilating properties were assessed on endothelium denuded strips of rat aorta Result. Some derivatives behave as well balanced "hybrids" displaying NO-dependent vasodilating and beta-blocking properties in the same concentration range. Some others display either prevalent beta-blocking or vasodilating activity. Generally speaking hybrid formation lowers the affinity for beta-receptors, in particular for beta(2)-type, to give an increase in beta(1)/beta(2) selectivity. Conclusions. The furoxan system is a flexible tool in designing analogues of propranolol whose NO-donating and beta-blocking properties are modulated over a wide range.
引用
收藏
页码:1750 / 1758
页数:9
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