3 Recent Advances in β-Adrenergic Blocking Agents

Main, Brian G.; Tucker, Howard

doi:10.1016/s0079-6468(08)70230-3

Cited by 19 publications

(10 citation statements)

References 150 publications

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“…3. A confirmation of this hypothesis can be found in the high lipophilicity and 82selectivity of compounds IPS 339 and ICI 118 551 (Bree et al 1986;Main &Tucker 1985). This rule however may not be a general one being seemingly restricted to /3-adrenoceptor ligands displaying an isopropyl or t-butyl amino substituent.…”

Section: Fig 2 Eudismic Analysis (Plots Of El Vs ~K E ) For the Amentioning

confidence: 88%

“…This "anti-Pfeiffer" behaviour is believed to result from increased affinity of the distomers when they display additional weak bonds with the receptor (mainly hydrophobic interactions) not occurring with the eutomers (Van de Waterbeemd et al 1987). Such additional interactions may well account for the fact that the enantiomers of the highly lipophilic, /&-selective agent IPS 339 display almost identical affinities (Main & Tucker 1985).…”

Section: Fig 2 Eudismic Analysis (Plots Of El Vs ~K E ) For the Amentioning

confidence: 99%

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Influence of Lipophilicity and Chirality on the Selectivity of Ligands for β1- and β2-Adrenoceptors

Tayar

Testa

Waterbeemd

et al. 1988

Journal of Pharmacy and Pharmacology

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Eudismic and QSAR analyses are reported for the beta 1- and beta 2-adrenoceptor affinities and beta 1-selectivity of 10 enantiomeric pairs of ligands with only N-isopropyl or N-t-butyl groups. For both receptors, the eudismic index (ratio of affinity) increases with the affinity of the eutomers. However, the affinity of the distomers for the beta 2-adrenoceptor is relatively high, suggesting additional hydrophobic interactions. This is confirmed by various correlations between affinities and lipophilicities, showing that the affinity for beta 2-adrenoceptors is slightly more dependent on lipophilicity than that for beta 1-adrenoceptors. As a result, the beta 1-selectivity of the investigated beta 1-adrenoceptor ligands is strongly and negatively correlated with their lipophilicity (r = -0.942).

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Section: Fig 2 Eudismic Analysis (Plots Of El Vs ~K E ) For the Amentioning

confidence: 88%

Section: Fig 2 Eudismic Analysis (Plots Of El Vs ~K E ) For the Amentioning

confidence: 99%

Influence of Lipophilicity and Chirality on the Selectivity of Ligands for β1- and β2-Adrenoceptors

Tayar

Testa

Waterbeemd

et al. 1988

Journal of Pharmacy and Pharmacology

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“…Structure-activity analysis of AR ligands has shown the amine moiety of both agonists and antagonists to be essential for the interaction with the >-ARs (20,21 (23). Thus, these catechol ring and hydroxyl group interactions would serve to specifically orient the catechol ring of the agonist in the binding site of the receptor (24).…”

Section: Important Interaction Sites Between Ligands and -Ar Subtypementioning

confidence: 99%

β -Adrenoceptors: Three-Dimensional Structures and Binding Sites for Ligands

Nagatomo

Ohnuki

Ishiguro

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-Recent progress in analyzing the structures and functions of G-protein coupled receptors (GPCRs) including > -adrenoceptors (>-ARs) has been made by pharmacological, physiological and molecular biological techniques. The three-dimensional (3D) structures, interaction sites with ligands and conformational changes of these receptor subtypes due to ligand binding are now better understood by the simulation of these receptors using computer-aided molecular modeling. Based on these techniques, numbers and conformations of amino acid sequences of each subtype (> 1-, >2-and >3-ARs) were defined and also interaction sites or modes of interaction between ligands and >-ARs could be analyzed three-dimensionally. In addition, simulation of 3D structures of > -ARs by molecular modeling could clearly determine the limited size, space or pocket for fitting with ligands. These studies will give some clues for the clarification of other GPCRs. Thus, this review summarizes current findings on chemical structures of ligands, amino acid sequences, 3D structures and important amino acids of >-AR subtypes for interacting with ligands obtained from mutagenesis, chimeric studies and molecular modeling techniques.

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“…Introduction. ± b-Blockers are widely used in the treatment of various cardiovascular diseases such as hypertension, angina pectoris, and cardiac arrhythmias [1] [2] (Fig. 1).…”

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confidence: 99%