From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

From Methaqualone and Beyond : Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors. / Wang, Peng-Fei; Jensen, Anders A; Bunch, Lennart.

In: ACS Chemical Neuroscience, Vol. 11, No. 24, 2020, p. 4362-4375.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wang, P-F, Jensen, AA & Bunch, L 2020, 'From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors', ACS Chemical Neuroscience, vol. 11, no. 24, pp. 4362-4375. https://doi.org/10.1021/acschemneuro.0c00600

APA

Wang, P-F., Jensen, A. A., & Bunch, L. (2020). From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors. ACS Chemical Neuroscience, 11(24), 4362-4375. https://doi.org/10.1021/acschemneuro.0c00600

Vancouver

Wang P-F, Jensen AA, Bunch L. From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors. ACS Chemical Neuroscience. 2020;11(24):4362-4375. https://doi.org/10.1021/acschemneuro.0c00600

Author

Wang, Peng-Fei ; Jensen, Anders A ; Bunch, Lennart. / From Methaqualone and Beyond : Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors. In: ACS Chemical Neuroscience. 2020 ; Vol. 11, No. 24. pp. 4362-4375.

Bibtex

@article{0d184b7310c7426491046fce68c17aa0,
title = "From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors",
abstract = "Methaqualone (2-methyl-3-(o-tolyl)-quinazolin-4(3H)-one, MTQ) is a moderately potent positive allosteric modulator (PAM) of GABAA receptors (GABAARs). In a previous structure-activity relationship (SAR) study probing the importance of 2- and 3-substituents in the quinazolin-4(3H)-one scaffold, several potent GABAAR PAMs were identified, including 2,3-diphenylquinazolin-4(3H)-one (PPQ) and 3-(2-chlorophenyl)-2-phenylquinazolin-4(3H)-one (Cl-PPQ). Here, PPQ was applied as lead in a SAR study of 6-, 7-, and 8-substituents in the quinazolin-4(3H)-one by synthesis and functional characterization of 36 PPQ analogs at various GABAAR subtypes. While none of the new analogs were significantly more potent than PPQ or displayed pronounced subtype selectivity across the GABAARs tested, several interesting SAR observations were extracted from the study. In an in silico study, the putative binding modes of MTQ, PPQ, and Cl-PPQ in the transmembrane β2(+)/α1(-) interface of the α1β2γ2S GABAAR were predicted. Several plausible binding modes were identified for the three PAMs, and rationalization of the molecular basis for their different modulatory potencies was attempted.",
author = "Peng-Fei Wang and Jensen, {Anders A} and Lennart Bunch",
year = "2020",
doi = "10.1021/acschemneuro.0c00600",
language = "English",
volume = "11",
pages = "4362--4375",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "24",

}

RIS

TY - JOUR

T1 - From Methaqualone and Beyond

T2 - Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA Receptors

AU - Wang, Peng-Fei

AU - Jensen, Anders A

AU - Bunch, Lennart

PY - 2020

Y1 - 2020

N2 - Methaqualone (2-methyl-3-(o-tolyl)-quinazolin-4(3H)-one, MTQ) is a moderately potent positive allosteric modulator (PAM) of GABAA receptors (GABAARs). In a previous structure-activity relationship (SAR) study probing the importance of 2- and 3-substituents in the quinazolin-4(3H)-one scaffold, several potent GABAAR PAMs were identified, including 2,3-diphenylquinazolin-4(3H)-one (PPQ) and 3-(2-chlorophenyl)-2-phenylquinazolin-4(3H)-one (Cl-PPQ). Here, PPQ was applied as lead in a SAR study of 6-, 7-, and 8-substituents in the quinazolin-4(3H)-one by synthesis and functional characterization of 36 PPQ analogs at various GABAAR subtypes. While none of the new analogs were significantly more potent than PPQ or displayed pronounced subtype selectivity across the GABAARs tested, several interesting SAR observations were extracted from the study. In an in silico study, the putative binding modes of MTQ, PPQ, and Cl-PPQ in the transmembrane β2(+)/α1(-) interface of the α1β2γ2S GABAAR were predicted. Several plausible binding modes were identified for the three PAMs, and rationalization of the molecular basis for their different modulatory potencies was attempted.

AB - Methaqualone (2-methyl-3-(o-tolyl)-quinazolin-4(3H)-one, MTQ) is a moderately potent positive allosteric modulator (PAM) of GABAA receptors (GABAARs). In a previous structure-activity relationship (SAR) study probing the importance of 2- and 3-substituents in the quinazolin-4(3H)-one scaffold, several potent GABAAR PAMs were identified, including 2,3-diphenylquinazolin-4(3H)-one (PPQ) and 3-(2-chlorophenyl)-2-phenylquinazolin-4(3H)-one (Cl-PPQ). Here, PPQ was applied as lead in a SAR study of 6-, 7-, and 8-substituents in the quinazolin-4(3H)-one by synthesis and functional characterization of 36 PPQ analogs at various GABAAR subtypes. While none of the new analogs were significantly more potent than PPQ or displayed pronounced subtype selectivity across the GABAARs tested, several interesting SAR observations were extracted from the study. In an in silico study, the putative binding modes of MTQ, PPQ, and Cl-PPQ in the transmembrane β2(+)/α1(-) interface of the α1β2γ2S GABAAR were predicted. Several plausible binding modes were identified for the three PAMs, and rationalization of the molecular basis for their different modulatory potencies was attempted.

U2 - 10.1021/acschemneuro.0c00600

DO - 10.1021/acschemneuro.0c00600

M3 - Journal article

C2 - 33170625

VL - 11

SP - 4362

EP - 4375

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 24

ER -

ID: 251307098