title: Synthesis and cardiovascular activity of metoprolol analogues.
abstract: The synthesis of four novel analogues of metoprolol, a well-known beta1-blocker used to reduce arterial blood pressure, is described. The preparation of (2S,2'S)-7, (2R,2'S)-7, (2R,2'R)-8, and (2S,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 beta1 and beta2 adrenergic receptor.
authors.affiliation: Facultad de Estudios Superiores-Zaragoza, Universidad Nacional Autónoma de México, 09230 Mexico, D.F., México.
authors.forename: Roberto
authors.initials: R
authors.lastname: Melgar-Fernández
authors.forename: Patricia
authors.initials: P
authors.lastname: Demare
authors.forename: Enrique
authors.initials: E
authors.lastname: Hong
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Rosas
authors.forename: Jaime
authors.initials: J
authors.lastname: Escalante
authors.forename: Omar
authors.initials: O
authors.lastname: Muñoz-Muñiz
authors.forename: Eusebio
authors.initials: E
authors.lastname: Juaristi
authors.forename: Ignacio
authors.initials: I
authors.lastname: Regla
mesh_terms: D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats
chemical_list: D008790:Metoprolol; D002122:Calcium Chloride