Synthesis and vasorelaxant properties of hybrid molecules out of NO-donors and the β-receptor blocking drug propranolol

被引：14

作者：

Decker, M ^{[1
]}

König, A ^{[1
]}

Glusa, E ^{[1
]}

Lehmann, J ^{[1
]}

机构：

[1] Univ Jena, Lehrstuhl Pharmazeut Med Chem, Inst Pharm, D-07743 Jena, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 19期

关键词：

hybrids; propranolol; NO-donors; vasorelaxation;

D O I：

10.1016/j.bmcl.2004.07.014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

S-Nitroso-N-acetylpenicillamine (SNAP) and 3-nitrooxypivaloyl acid were combined in the form of the respective amides with propranolol, in order to obtain prodrugs (NO-propranololes) with beta-receptor blocking properties of the latter compound with nitric oxide releasing properties of the former compounds. A respective nitratoester could not be synthesized, because it immediately rearranges to the amide after deprotection of the amino group. In vitro tests on porcine pulmonary arteries showed that both types of hybrid molecules (6, 12) elicited vasorelaxation, but the nitratoamide was less potent by more than one order of magnitude. The vasorelaxant effect of SNAP was more pronounced than that of the SNAP-hybrid (12), on the other hand the nitratoamide 6 was more potent than 3-nitrooxypivaloyl acid. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4995 / 4997

页数：3

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