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

Basic Information

ID: ALA1137883

Journal: Bioorg Med Chem Lett

Title: Synthesis and vasorelaxant properties of hybrid molecules out of NO-donors and the beta-receptor blocking drug propranolol.

Authors: Decker M, König A, Glusa E, Lehmann J.

Abstract: 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.

CiteXplore: 15341967

DOI: 10.1016/j.bmcl.2004.07.014

Patent ID: