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

Amour, Augustin and Barton, Nick and Cooper, Anthony W.J. and Inglis, Graham and Jamieson, Craig and Luscombe, Christopher N. and Perez, David and Peace, Simon and Rowland, Paul and Tame, Chris and Uddin, Sorif and Vitulli, Giovanni and Wellaway, Natalie (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. ISSN 0022-2623 (https://doi.org/10.1021/acs.jmedchem.6b00799)

[thumbnail of Amour-etal-JMC2016-Novel-orally-bioavailable-series-of-PI3Kδ-inhibitors]
Preview
 Text. Filename: Amour_etal_JMC2016_Novel_orally_bioavailable_series_of_PI3K_inhibitors.pdf
Accepted Author Manuscript
Download (1MB)| Preview

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.

ORCID iDs

Amour, Augustin, Barton, Nick, Cooper, Anthony W.J., Inglis, Graham, Jamieson, Craig ORCID logoORCID: https://orcid.org/0000-0002-6567-8272, Luscombe, Christopher N., Perez, David, Peace, Simon, Rowland, Paul, Tame, Chris, Uddin, Sorif, Vitulli, Giovanni and Wellaway, Natalie;
  • Item type:Article
    ID code:57124
    Dates:
    Date
    Event
    18 July 2016
    Published
    18 July 2016
    Published Online
    18 July 2016
    Accepted
    Notes: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
    Keywords:PI3Kδ inhibitors, respiratory disease, bioavailability, deconstruction, hinge-binding groups, optimisation, indazole core, physicochemical properties, pharmacokinetic properties, Pharmacy and materia medica, Drug Discovery, Molecular Medicine
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:27 Jul 2016 08:33
    Last modified:24 Apr 2022 00:36
    URI:https://strathprints.strath.ac.uk/id/eprint/57124
CORE (COnnecting REpositories)