Hydrogen-Bond Accepting Properties of New Heteroaromatic Ring Chemical Motifs: A Theoretical Study

Journal of Chemical Information and Modeling
Jérôme GratonPaul L A Popelier

Abstract

The prediction of hydrogen-bond (H-bond) acceptor ability is crucial in drug design. This important property is quantified in a large pKBHX database of consistently measured values. We aim to expand the chemical diversity of the studied H-bond acceptors and to increase the range of H-bond strength considered. Two quantum chemical descriptors are contrasted, called ΔE(H) (the change in the energy of a topological hydrogen atom upon complexation) and Vmin (the local minimum in the electrostatic potential on the H-bond accepting site). We performed a systematic analysis of the correlations between pKBHX and Vmin for an initial set of 106 compounds (including O- and N-containing subsets, as well as compounds including sulfur, chlorine, and π-bases). Correlations improve for family dependent subsets, and after outlier treatment, a set of 90 compounds was used to set up a linear equation to predict pKBHX from Vmin. This equation and a previously published equation [Green and Popelier J. Chem. Inf. 2014, 54 (2), 553-561], to predict pKBHX from ΔE(H), were used to predict the pKBHX values for 22 potentially biologically active heteroaromatic ring compounds, [Pitt et al. J. Med. Chem. 2009, 52 (9), 2952-2963], among which several struct...Continue Reading

References

Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
May 12, 2001·The Journal of Organic Chemistry·M H Abraham, J A Platts
Feb 15, 2002·Chemistry : a European Journal·Olivier Lamarche, James A Platts
Jan 28, 2003·Drug Discovery Today·Michael H AbrahamDerek P Reynolds
May 25, 2004·Journal of Chemical Information and Computer Sciences·Alexander A OliferenkoAlan R Katritzky
Jun 19, 2008·Journal of Medicinal Chemistry·Anita ToulminPeter W Kenny
Oct 24, 2008·Chemistry : a European Journal·François BesseauMichel Berthelot
Nov 28, 2008·Journal of Computational Chemistry·Johannes SchwöbelGerrit Schüürmann
Mar 20, 2009·Journal of Chemical Information and Modeling·Johannes SchwöbelGerrit Schüürmann
Apr 8, 2009·Journal of Medicinal Chemistry·William R PittColin R Groom
Apr 23, 2009·Journal of Chemical Information and Modeling·Peter W Kenny
Jun 23, 2009·Journal of Medicinal Chemistry·Christian LaurenceEric Renault
Aug 22, 2009·The Journal of Physical Chemistry. a·Johannes SchwöbelGerrit Schüürmann
Sep 1, 2009·Journal of Chemical Information and Modeling·Monika NockerKlaus R Liedl
Oct 17, 2009·Journal of Medicinal Chemistry·Andrew R LeachRobin Taylor
Mar 30, 2010·Journal of Medicinal Chemistry·Caterina BissantzMartin Stahl
Aug 17, 2010·The Journal of Physical Chemistry. a·Katharina WendlerBarbara Kirchner
Sep 3, 2011·Chemistry : a European Journal·Alexandre P AtkinsonJérôme Graton
Sep 29, 2012·ACS Chemical Neuroscience·Jean-Louis Reymond, Mahendra Awale
Apr 5, 2013·Physical Chemistry Chemical Physics : PCCP·Andreas KlamtJean-Yves Le Questel
May 8, 2013·Journal of Medicinal Chemistry·Yansong WangFelix Hausch
Dec 3, 2013·Journal of Chemical Information and Modeling·Ahmed El KerdawyThomas Fox
Jan 28, 2014·Journal of Chemical Information and Modeling·Anthony J Green, Paul L A Popelier
Jan 30, 2014·Journal of Medicinal Chemistry·Richard D TaylorAlastair D G Lawson
Mar 19, 2014·Conservation Biology : the Journal of the Society for Conservation Biology·Jordan T Watson, Keith A Bigelow
Jan 7, 2015·Journal of Chemical Information and Modeling·Obdulia RabalJulen Oyarzabal
May 9, 2015·Canadian Journal of Public Health = Revue Canadienne De Santé Publique·Hmwe Hmwe KyuMichael H Boyle
May 1, 2005·Journal of Chemical Theory and Computation·Yan Zhao, Donald G Truhlar

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Citations

Feb 13, 2016·Journal of Medicinal Chemistry·Peter W KennyGeraldo Rodrigues Sartori
Nov 27, 2018·Molecular Informatics·Christoph A BauerAndreas H Göller
Dec 1, 2018·Chemistry, an Asian Journal·Adil AlkaşShane G Telfer
Jan 6, 2017·Journal of Computer-aided Molecular Design·Nádia Melo BorgesGeraldo Rodrigues Sartori
Jul 22, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·José Tiago M CorreiaMárcio W Paixão
Mar 7, 2020·Journal of Chemical Information and Modeling·Johannes R LoefflerKlaus R Liedl
Apr 11, 2020·Journal of Medicinal Chemistry·Martin Juhás, Jan Zitko
Feb 28, 2020·Journal of Chemical Theory and Computation·Diogo Santos-Martins, Stefano Forli
Oct 1, 2019·Journal of Chemical Information and Modeling·Johannes R LoefflerKlaus R Liedl

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