title: Beta-adrenoceptor activity of the stereoisomers of the bufuralol alcohol and ketone metabolites.
abstract: The stereoisomers of 2-[(tert-butylamino)methyl]-7-methyl-2,7-benzofurandimethanol (2) and 2-[2-(tert-butylamino)-1-hydroxyethyl]-7-benzofuranyl methyl ketone (3), the alcohol and ketone metabolites of bufuralol, have been prepared and examined for beta-adrenoceptor activity in rats. All the stereoisomers with the S configuration hydroxylamine side chain showed potent beta 2-antagonist activity comparable to (S)-bufuralol (1a). In contrast, a wide range of antagonist potencies was observed at the beta 1-receptor; only alcohol diastereomer 9a was more active than 1a. This suggests that the shape of the 7-substituent in these benzofurans influences the degree of interaction with the beta 1-receptor much more than with the beta 2-receptor. Partial beta 1-agonist activity was associated not only with all the stereoisomers with the S configuration hydroxylamine side chain but also with some of the R configuration derivatives, especially (R)-ketone 3b. The results suggest that the margin of difference in beta-adrenoceptor activity between compounds epimeric at the hydroxylamine side chain can be significantly influenced by a suitable substituent in the aromatic nucleus.
authors.forename: P J
authors.initials: PJ
authors.lastname: Machin
authors.forename: D N
authors.initials: DN
authors.lastname: Hurst
authors.forename: J M
authors.initials: JM
authors.lastname: Osbond
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004983:Ethanolamines / Q000138:chemical synthesis / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008968:Molecular Conformation; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C047237:2-(2-(tert-butylamino)-1-hydroxyethyl)-7-benzofuranyl methyl ketone; C010831:bufuralol; C047236:2-((tert-butylamino)methyl)-7-methyl-2,7-benzofurandimethanol; D007545:Isoproterenol