Výsledky vyhledávání - "Davina Humphreys"

Highly tractable, sub-nanomolar non-steroidal glucocorticoid receptor agonists

Autor: Diane M. Coe, Simon J. F. Macdonald, Davina Humphreys, Philip Alan Skone, Haydn Terence Jones, George Hardy, Iain M. McLay, Annette Miles-Williams, David House, Matilde Caivano, Iain Uings, Keith Biggadike, Margaret Clackers, Vicki Weller

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 19:4846-4850

Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NFκB agonist activity was optimised in an iterative process from pIC50 7.5 (for 7), to pIC50 10.1 (for 38E1). An explanation for the SAR observed based is presented a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2bb7fb2263d54a89f13a1a813d392687
https://doi.org/10.1016/j.bmcl.2009.06.020

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Non-steroidal glucocorticoid agonists—The discovery of aryl pyrazoles as A-ring mimetics

Autor: Philip Alan Skone, Iain Uings, Davina Humphreys, Diane M. Coe, George Hardy, Simon J. F. Macdonald, Doug J. Minick, Richard Loiseau, Haydn Terence Jones, Iain M. McLay, David House, Derek A. Demaine, Michael John Johnston, Graham G. A. Inglis, Margaret Clackers

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 17:4737-4745

Starting from an established series of non-steroidal glucocorticoid receptor (GR) agonists, a large array was designed where a metabolically labile benzoxazinone moiety was replaced. Initial hits bound to GR but lacked agonist activity. Following two

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7af2969a44c8092b71ad2b92bf33afeb
https://doi.org/10.1016/j.bmcl.2007.06.066

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Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series

Publikováno v: Journal of Medicinal Chemistry. 49:4216-4231

The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f39bc2e216c3f76a792ae67a2aa0cf0
https://doi.org/10.1021/jm060302x

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The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase—GW311616A a development candidate

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 11:895-898

The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b569e3c9519903b411ede0c093223361
https://doi.org/10.1016/s0960-894x(01)00078-6

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Nonsteroidal glucocorticoid agonists: tetrahydronaphthalenes with alternative steroidal A-ring mimetics possessing dissociated (transrepression/transactivation) efficacy selectivity

Autor: Graham G. A. Inglis, George Hardy, Philip Alan Skone, Simon J. F. Macdonald, Gemma Veitch, Diane M. Coe, Haydn Terence Jones, Iain M. McLay, Margaret Clackers, Derek A. Demaine, Richard Loiseau, Gordon G. Weingarten, Iain Uings, Keith Biggadike, Michael John Johnston, Deborah Needham, Mohamed Boudjelal, David House, Davina Humphreys

Publikováno v: Journal of medicinal chemistry. 50(26)

The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB glucocorticoid receptor (GR

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::115426c12ab95211a36eb403ee230f71
https://pubmed.ncbi.nlm.nih.gov/18038970

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Design and synthesis of new nonsteroidal glucocorticoid modulators through application of an 'agreement docking' method

Autor: Victoria Vinader, Davina Humphreys, Philip Alan Skone, Iain M. McLay, John Martin Pritchard, Derek A. Demaine, Michael John Johnston, Stephen E. Shanahan, Haydn Terence Jones, Mark Salter, Francois Pacquet, Iain Uings, Simon J. F. Macdonald, Mike D. Barker, Margaret Clackers

Publikováno v: Journal of medicinal chemistry. 48(14)

Structurally related glucocorticoid receptor (GR) binders were docked into the GR active site to select the binding mode closest to the true docking mode. This process, termed an “agreement docking method”, led to the design of tetrahydronaphthal

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3099406091e183a549563421ded2017d
https://pubmed.ncbi.nlm.nih.gov/15999989

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Discovery of further pyrrolidine trans-lactams as inhibitors of human neutrophil elastase (HNE) with potential as development candidates and the crystal structure of HNE complexed with an inhibitor (GW475151)

Autor: Alan J. Wonacott, Rosalind E Godward, Gill Fleetwood, Robin Andrew Smith, Pritom Shah, Simon J. F. Macdonald, Martin R. Johnson, Christopher R Molloy, George Hardy, Simon Teanby Hodgson, Lee Andrew Harrison, Augustin Amour, Michael Dennis Dowle, Onkar M. P. Singh, Graham G. A. Inglis, Mary Dixon, Davina Humphreys, Geoffrey D. Clarke

Publikováno v: Journal of medicinal chemistry. 45(18)

Described herein is a modern approach to the rapid preparation and evaluation of compounds as potential back-up drug candidates. GW311616A, 1, a derivative of pyrrolidine trans-lactams, has previously been described as a potent, orally active inhibit

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6e1425c075142ba7c2e8a8c997cbf79
https://pubmed.ncbi.nlm.nih.gov/12190311

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Corrigendum to 'Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams'

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 11:1249

Simon J. F. Macdonald,* Michael D. Dowle, Lee A. Harrison, Julie E. Spooner, Pritom Shah, Martin R. Johnson, Graham G. A. Inglis, Geoffrey D. E. Clarke, David J. Belton, Robin A. Smith, Christopher R. Molloy, Mary Dixon, Graham Murkitt, Rosalind E. G

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::ba373c9e0460e2f238793190965b3847
https://doi.org/10.1016/s0960-894x(01)00175-5

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Akademický článek

Nonsteroidal Glucocorticoid Agonists: Tetrahydronaphthalenes with Alternative Steroidal A-Ring Mimetics Possessing Dissociated (Transrepression/Transactivation) Efficacy Selectivity.

Autor: Keith Biggadike, Mohamed Boudjelal, Margaret Clackers, Diane M. Coe, Derek A. Demaine, George W. Hardy, Davina Humphreys, Graham G. A. Inglis, Michael J. Johnston, Haydn T. Jones, David House, Richard Loiseau, Deborah Needham, Philip A. Skone, Iain Uings, Gemma Veitch, Gordon G. Weingarten, Iain M. McLay, Simon J. F. Macdonald

Publikováno v: Journal of Medicinal Chemistry; Nov2007, Vol. 50 Issue 26, p6519-6534, 16p

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