Nitrogen-containing Chain Research Articles

Synthesis and Cardiovascular Activity of Metoprolol Analogues.

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Synthesis and cardiovascular activity of metoprolol analogues

The synthesis of four novel analogues of metoprolol, a well-known β 1-blocker used to reduce arterial blood pressure, is described. The preparation of (2 S,2′ S)- 7, (2 R,2′ S)- 7, (2 R,2′ R)- 8, and (2 S,2′ R)- 8 was based on the reaction of racemic 2-[4-(2′-methoxyethyl)-phenoxymethyl]-oxirane ( 4) with ( R)- or ( S)-2-amino-1-butanol. Salient characteristics of analogues 7 and 8 relative to metoprolol are the incorporation of an additional stereogenic center, as well as a methyl group and a hydroxyl function on the nitrogen-containing chain. These novel derivatives present significant hypotensive and bradycardiac activity, although no blocking action toward β 1 and β 2 adrenergic receptor.