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Louis SN, Nero TL, Iakovidis D, et al. beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines. Eur J Med Chem. 1999;34(11):919-937doi: 10.1016/s0223-5234(99)00114-2.
Louis, S. N., Nero, T. L., Iakovidis, D., Colagrande, F. M., Jackman, G. P., & Louis, W. J. (1999). beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines. European journal of medicinal chemistry, 34(11), 919-937. https://doi.org/10.1016/s0223-5234(99)00114-2
Louis, et al. "beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines." European journal of medicinal chemistry vol. 34,11 (1999): 919-937. doi: https://doi.org/10.1016/s0223-5234(99)00114-2
Louis SN, Nero TL, Iakovidis D, Colagrande FM, Jackman GP, Louis WJ. beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines. Eur J Med Chem. 1999 Nov 01;34(11):919-937. doi: 10.1016/s0223-5234(99)00114-2. PMID: 10889317.
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Eur J Med Chem. 1999 Nov 01;34(11):919-937. doi: 10.1016/s0223-5234(99)00114-2.

beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines.

European journal of medicinal chemistry

Louis, Nero, Iakovidis, Colagrande, Jackman, Louis

Affiliations

  1. Clinical Pharmacology and Therapeutics Unit, The University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre 3084, Victoria, Heidelberg, Australia

PMID: 10889317 DOI: 10.1016/s0223-5234(99)00114-2

Abstract

To further explore the structure-activity relationships of beta-adrenoceptor (beta-AR) antagonists, a series of 25 para-substituted N-isopropylphenoxy-propanolamines were synthesised, nine of which are new compounds. All have been examined for their ability to antagonise beta(1)-ARs in rat atria and beta(2)-ARs in rat trachea. Substitution in the para-position of the phenyl ring is thought to confer beta(3)-specificity and the selectivity of these compounds for the beta(1)-AR ranges from 1.5-234. None of the compounds tested were selective for the beta(2)-AR. Of the 25 compounds studied, 22 had reasonable (pA(2) > 7) potencies for the rat beta(1)-AR. Only compound 1 displayed reasonable (pA(2) > 7) potency for the rat beta(2)-AR. Twenty two compounds were used as the training set for comparative molecular field analysis (CoMFA) of antagonist potency (pA(2)) at the rat beta(1)- and beta(2)-ARs. The inclusion of a number of additional physical characteristics improved the QSAR analysis over models derived solely using the CoMFA electrostatic and steric fields. The final models predicted the beta(1)- and beta(2)-AR potency of the compounds in the training set with high accuracy (r(2) = 0.93 and 0.86 respectively). The final beta(1)-AR model predicted the beta(1)-potencies of two out of the three test compounds, not included in the training set, with residual pA(2) values < -0.14, whereas the test compounds were not as well predicted by our final beta(2)-AR model (residual pA(2) values < -0.38).

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