A quantum-chemical and experimental study of the hallucinogen (±)-1-(2,5-dimethoxy-4-nitrophenyl)-2-aminopropane (DON)

Gómez-Jeria, Juan S.; Cassels, Bruce K.; Saavedra-Aguilar, Juan C.

doi:10.1016/0223-5234(87)90032-8

Cited by 21 publications

(15 citation statements)

References 16 publications

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“…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].…”

Section: Theoretical Background 21 the Modelmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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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

2013

Can Chem Trans

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Abstract:The general hypothesis that any in vitro or in vivo biological activity can be explained only in terms of local atomic reactivity indices has been proposed and tested for the inhibition of HIV-1 WT replication by some phenylaminopyridine derivatives and the inhibition of cell growth by several 1-azabenzanthrone derivatives. In all of them good structure-activity relationships have been obtained and some requirements for potent biological activity have been suggested. For the cases tested here the common skeleton hypothesis works well. As this hypothesis has a logical conceptual basis but does not yet have a formal general mathematical background, it cannot be generalized and must be tested case by case.This methodology gives an account of the whole process and, in the case of multi-step processes, is unable to relate the different reactivity indices appearing in the SAR equations to any particular step.

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Section: Theoretical Background 21 the Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2013

Can Chem Trans

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“…As the method employed here has been discussed in great detail in this Journal 2-6 and elsewhere [7][8][9][10][11][12][13][14] , we shall only present a brief sketch here. Within the Klopman-Peradejordi-Gómez (KPG) model 15 , and for a group of molecules having a common skeleton and interacting with the same receptor, it can be shown that the affinity constant (K) can be expressed as 15 :…”

Section: Methods Models and Calculationsmentioning

confidence: 99%

A DFT Study of the Relationships Between Electronic Structure and Peripheral Benzodiazepine Receptor Affinity in a Group of N,n-Dialkyl-2-Phenylindol-3-Ylglyoxylamides

Gómez-Jeria

2010

J. Chil. Chem. Soc.

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We present here the results of a Density Functional Theory study of the relationships between electronic structure and peripheral benzodiazepine receptor affinity for a group of n,n-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives. As expected for a receptor that evolved over many millions of years, the interaction is charge-and orbital-controlled because it involves net charges and reactivity indices from definite molecular orbitals. The conditions for high receptor affinity are obtained and commented on. A partial pharmacophore model is suggested and discussed. This is the first time that an all-electron calculation combined with a model-based method is employed in QSAR studies.

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“…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 .…”

Section: Methods Models and Calculationsmentioning

confidence: 99%

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

Vega

Alarcón

Gómez-Jeria

2013

J. Chil. Chem. Soc.

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This paper uses newly developed and extended quantum chemical methods in an attempt to advance the knowledge of the relationship between the variation of several local atomic descriptors of the electronic structure and the variation of the inhibitory capacity of a group of reversible and irreversible inhibitors of hepatitis C virus NS5B polymerase. Good structure-activity relationships were obtained for both kinds of compounds. Some processes are charge-, orbital-and/or steric-controlled. The action mechanisms seem to be different for reversible and irreversible inhibitors. Also, good QSAR equations were obtained for the activities of these compounds in a cellular replicon assay and for pharmacokinetic profiles. The local atomic hardness seems to give a good account of the interaction of the drugs with apolar sites of the partner (enzyme, receptor, etc.). This is the first time that a purely quantum-chemical index is able to deal directly with this kind of interaction.

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A quantum-chemical and experimental study of the hallucinogen (±)-1-(2,5-dimethoxy-4-nitrophenyl)-2-aminopropane (DON)

Cited by 21 publications

References 16 publications

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

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

A DFT Study of the Relationships Between Electronic Structure and Peripheral Benzodiazepine Receptor Affinity in a Group of N,n-Dialkyl-2-Phenylindol-3-Ylglyoxylamides

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

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