Stereochemical comparison of nebivolol with other beta-blockers.
beta-Blockers are widely used in the treatment of cardiovascular disease and act by antagonizing the effects of adrenaline (epinephrine) and noradrenaline (norepinephrine) on beta-adrenergic receptors. All beta-blockers currently used in the treatment of cardiovascular disease contain at least one chiral center and, while most are marketed as racemates, their cardiac antihypertensive activity generally resides in the S-enantiomer. Nebivolol is a third generation beta-blocker that is highly selective for the beta(1)-adrenoceptor. The nebivolol molecule contains four chiral centers and is marketed as a racemate of (+)-nebivolol (SRRR-configuration) and (-)-nebivolol (RSSS-configuration). Nebivolol differs from all other beta-blockers with a hydroxypropanolamine substructure in that its cardiac antihypertensive activity resides in the R-enantiomer at the hydroxy group, whereas all other beta-blockers have antihypertensive activity in the S-enantiomer. Two of the four chiral centers in nebivolol are part of a ring structure and the increased rigidity of this structure may be related to nebivolol's divergence from the standard pharmacophore model of beta-blockers.
Siebert
Carsten D
CD
Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany. dr.cdsiebert@web.de
Hänsicke
André
A
Nagel
Thomas
T
D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D004983:Ethanolamines / Q000737:chemistry* / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D000068577:Nebivolol; D011941:Receptors, Adrenergic / Q000378:metabolism; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D011941:Receptors, Adrenergic; D000068577:Nebivolol