Computer-aided mapping of the beta-adrenoceptor. 1. Explanation for effect of para substitution on blocking activity at the beta-1-adrenoceptor.

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Ball JB, Nero TL, Iakovidis D, Tung L, Jackman G, Louis WJ

Computer-aided mapping of the beta-adrenoceptor. 1. Explanation for effect of para substitution on blocking activity at the beta-1-adrenoceptor.

J Med Chem. 1992 Dec 11;35(25):4676-82.

PubMed ID

1361581 [ View in PubMed

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Abstract

Anomalously low affinities for the beta-1-adrenoceptor are seen for members of a series of para-substituted N-isopropylphenoxypropanolamines in which the substituent is able to conjugate with the aromatic ring. The energy of conjugation was calculated using the AM1 semiempirical molecular orbital method and appears to correlate with the loss of binding energy, and hence affinity for the receptor. This suggests that binding is associated with movement of the substituent out of the plane of the aromatic ring due to steric interference with the receptor. A previously unrecognized binding site for aromatic groups off the para position is also identified.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Atenolol	Beta-1 adrenergic receptor	Kd (nM)	158.49	N/A	N/A	Details
Betaxolol	Beta-1 adrenergic receptor	Kd (nM)	39.81	N/A	N/A	Details
Esmolol	Beta-1 adrenergic receptor	Kd (nM)	100	N/A	N/A	Details
Practolol	Beta-1 adrenergic receptor	Kd (nM)	1000	N/A	N/A	Details