Biomedical subjects

D N Hurst

Publications and source records attributed to D N Hurst.

4 recordsLinked to original sources

PubMed1985

Beta-adrenoceptor activity of the stereoisomers of the bufuralol alcohol and ketone metabolites.

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.

Adrenergic beta-Antagonists↗

PubMed1985

Lung function in the elderly.

Data are presented on the FEV1 and forced vital capacity (FVC) of elderly people living at home. These were derived from a survey of 418 persons over the age of 70 years and thus provide standards for the assessment of elderly persons. There was a decline in FEV1 and FVC cross sectionally with age and a continued adverse effect of smoking. A history of cough and phlegm was strongly related to impairment of lung function.

Aged↗

PubMed1984

Beta 1-selective adrenoceptor antagonists. 3. 4-Azolyl-linked phenoxypropanolamines.

A series of 4-substituted phenoxypropanolamines has been prepared and examined for beta-adrenoceptor activity. The 4-substituents, di- and triazole ring systems connected to the phenoxy ring by different length chains, were chosen as a means of introducing cardioselectivity. This has been achieved, especially in the 1-[4-[(4-chloropyrazol-1-yl)methoxy] phenoxy]-3-(isopropylamino)-2-propanol (11), the 4-[(2H-1,2,3-triazol-2-yl)methoxy] analogue (21), and the 4-[2-(2H-1,2,3-triazol-2-yl)ethoxy] analogue (22), which show potent beta 1-blockade with selectivity ratios in excess of 100:1. Structure-activity relationships are discussed, and the optimum position of the heteroatom in the 4-substituent is defined.

Adrenergic beta-Antagonists↗

PubMed1983

beta 1-selective adrenoceptor antagonists. 2. 4-ether-linked phenoxypropanolamines.

A series of 4-substituted phenoxypropanolamines was prepared and examined for beta-adrenoceptor activity. Some of the compounds, especially the [4-[2-[[2-(4-fluorophenyl)ethyl] oxy]ethoxy]phenoxy]propanolamines (14, 15, and 24), showed potent beta 1-blockade with virtually no beta 2-blockade at doses over a 1000 times greater. The compounds also possessed partial agonist activity. Structure-activity relationships are discussed, and conclusions are drawn about the binding sites on beta-adrenoceptors.

Adrenergic beta-Agonists↗