Quantum‐chemical study of the relation between electronic structure and pA₂ in a series of 5‐substituted tryptamines

Abstract

We have analyzed the dependence of the serotonin receptor binding affinity on the electronic and steric reactivity indexes for a group of 5-substituted tryptamines. The approaches employed are a new nonempirical Quantitative Structure-Activity relationship approach and multiple regression analyses. The results suggest that the variation of the receptor binding affinity in 5-substituted tryptamines is related to the variation of the net charge of two atoms and to the steric bulk of the N-substituent. A receptor model is proposed.

Quantum-chemical Modeling of the Relationships between Molecular Structure and In Vitro Multi-Step, Multimechanistic Drug Effects. HIV-1 Replication Inhibition and Inhibition of Cell Proliferation as Examples

“…This model has shown, beyond all rational doubt, that it can shed light on the detailed structure of the drug-receptor interaction, that it has predictive capacity [5,6,31] and is even able to detect erroneous experimental data [32]. The last paper not belonging to our group, and using the model we are using here, was published in 1979 [33].…”

“…During the last three decades we have developed a formal method [1] to correlate in vitro receptor binding affinity constants with the electronic structure and substituent orientational parameters of drug molecules [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. A formal or non-empirical method is based on the following philosophy: it begins by proposing a model to explain a given biological activity.…”

A Theoretical Study of the Relationships between Electronic Structure and CB1 and CB2 Cannabinoid Receptor Binding Affinity in a Group of 1-Aryl-5-(1-H-pyrrol-1-yl)-1-H-pyrazole-3-carboxamides

“…We have developed a formal model to correlate the in vitro drug-receptor affinity constant with the electronic and molecular structure [43][44][45][46]. This model has shown, beyond all reasonable doubt, that it can shed light on the fine structure of the drug-receptor interaction ( [20,[47][48][49][50][51][52][53][54][55][56] and references therein). As the last paper using this model and not belonging to our unit was published in 1979 we shall present in the following part the main lines of its development.…”

Quantum Chemical Study of the Relationships Between Electronic Structure and Pharmacokinetic Profile, Inhibitory Strength Toward Hepatitis C Virus Ns5b Polymerase and HCV Replicons of Indole-Based Compounds

“…We have called them orientational parameters 49 . This model has shown, beyond all reasonable doubt, that it can shed light on the detailed structure of the drugreceptor interaction for several kind of biomolecules and receptors 48,[56][57][58][59][60][61][62][63][64][65][66] , that it has predictive capacity [67][68][69] and is even able to detect erroneous experimental data 70 . The last paper employing this method and not belonging to our group was published in 1979 71 .…”