Evolution of a novel orally bioavailable series of PI3Kδ inhibitors from an inhaled lead for the treatment of respiratory disease.

Augustin Amour; Nick Barton; Anthony W.J. Cooper; Graham Inglis; Craig Jamieson; Christopher N. Luscombe; David Perez; Simon Peace; Paul Rowland; Chris Tame; Sorif Uddin; Giovanni Vitulli; Natalie Wellaway

doi:10.1021/acs.jmedchem.6b00799

Evolution of a novel orally bioavailable series of PI3Kδ inhibitors from an inhaled lead for the treatment of respiratory disease.

Augustin Amour, Nick Barton, Anthony W.J. Cooper, Graham Inglis, Craig Jamieson, Christopher N. Luscombe, David Perez, Simon Peace, Paul Rowland, Chris Tame, Sorif Uddin, Giovanni Vitulli, Natalie Wellaway

Pure And Applied Chemistry

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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Abstract

A four step process of high quality modelling of existing data, deconstruction, identification of replacement cores and an innovative synthetic re-growth strategy led to the rapid discovery of a novel oral series of PI3K δ inhibitors with promising selectivity and excellent in vivo characteristics.

Original language	English
Number of pages	34
Journal	Journal of Medicinal Chemistry
Early online date	18 Jul 2016
DOIs	https://doi.org/10.1021/acs.jmedchem.6b00799
Publication status	E-pub ahead of print - 18 Jul 2016

Keywords

PI3Kδ inhibitors
respiratory disease
bioavailability
deconstruction
hinge-binding groups
optimisation
indazole core
physicochemical properties
pharmacokinetic properties

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10.1021/acs.jmedchem.6b00799

Amour-etal-JMC2016-Novel-orally-bioavailable-series-of-PI3Kδ-inhibitorsAccepted author manuscript, 1.12 MB

Craig Jamieson
- craig.jamiesonstrath.acuk
- Pure And Applied Chemistry - Professor
- Health and Wellbeing
Person: Academic

Cite this

Amour, A., Barton, N., Cooper, A. W. J., Inglis, G., Jamieson, C., Luscombe, C. N., Perez, D., Peace, S., Rowland, P., Tame, C., Uddin, S., Vitulli, G., & Wellaway, N. (2016). Evolution of a novel orally bioavailable series of PI3Kδ inhibitors from an inhaled lead for the treatment of respiratory disease. Journal of Medicinal Chemistry. Advance online publication. https://doi.org/10.1021/acs.jmedchem.6b00799

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title = "Evolution of a novel orally bioavailable series of PI3Kδ inhibitors from an inhaled lead for the treatment of respiratory disease.",

abstract = "A four step process of high quality modelling of existing data, deconstruction, identification of replacement cores and an innovative synthetic re-growth strategy led to the rapid discovery of a novel oral series of PI3K δ inhibitors with promising selectivity and excellent in vivo characteristics.",

keywords = "PI3Kδ inhibitors, respiratory disease, bioavailability, deconstruction, hinge-binding groups, optimisation, indazole core, physicochemical properties, pharmacokinetic properties",

author = "Augustin Amour and Nick Barton and Cooper, \{Anthony W.J.\} and Graham Inglis and Craig Jamieson and Luscombe, \{Christopher N.\} and David Perez and Simon Peace and Paul Rowland and Chris Tame and Sorif Uddin and Giovanni Vitulli and Natalie Wellaway",

note = "This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright {\textcopyright} American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see https://dx.doi.org10.1021/acs.jmedchem.6b00799",

year = "2016",

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doi = "10.1021/acs.jmedchem.6b00799",

language = "English",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

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AU - Amour, Augustin

AU - Barton, Nick

AU - Cooper, Anthony W.J.

AU - Inglis, Graham

AU - Jamieson, Craig

AU - Luscombe, Christopher N.

AU - Perez, David

AU - Peace, Simon

AU - Rowland, Paul

AU - Tame, Chris

AU - Uddin, Sorif

AU - Vitulli, Giovanni

AU - Wellaway, Natalie

N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see https://dx.doi.org10.1021/acs.jmedchem.6b00799

PY - 2016/7/18

Y1 - 2016/7/18

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AB - A four step process of high quality modelling of existing data, deconstruction, identification of replacement cores and an innovative synthetic re-growth strategy led to the rapid discovery of a novel oral series of PI3K δ inhibitors with promising selectivity and excellent in vivo characteristics.

KW - PI3Kδ inhibitors

KW - respiratory disease

KW - bioavailability

KW - deconstruction

KW - hinge-binding groups

KW - optimisation

KW - indazole core

KW - physicochemical properties

KW - pharmacokinetic properties

U2 - 10.1021/acs.jmedchem.6b00799

DO - 10.1021/acs.jmedchem.6b00799

M3 - Article

SN - 0022-2623

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -

Evolution of a novel orally bioavailable series of PI3Kδ inhibitors from an inhaled lead for the treatment of respiratory disease.

Abstract

Keywords

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