Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma

  • J Med Chem. 2016 Mar 10;59(5):1727-46. doi: 10.1021/acs.jmedchem.5b01029.
Stuart T Onions  1 ,  Kazuhiro Ito  2 ,  Catherine E Charron  2 ,  Richard J Brown  1 ,  Marie Colucci  1 ,  Fritz Frickel  2 ,  George Hardy  2 ,  Kevin Joly  1 ,  John King-Underwood  3 ,  Yasuo Kizawa  4 ,  Ian Knowles  5 ,  P John Murray  2 ,  Andrew Novak  1 ,  Anjna Rani  1 ,  Garth Rapeport  2 ,  Alun Smith  1 ,  Peter Strong  2 ,  David M Taddei  1 ,  Jonathan G Williams  1
Affiliations
  • 1. Sygnature Discovery Limited, Biocity , Nottingham NG1 1GF, United Kingdom.
  • 2. RespiVert Limited , 2 Royal College Street, The London Bioscience Innovation Centre, London NW1 0NH, United Kingdom.
  • 3. CompChem Resource , Old Cottage Hospital, Homend, Ledbury, Herefordshire HR8 1ED, United Kingdom.
  • 4. Department of Physiology and Anatomy, Nihon University School of Pharmacy , 7-7-1, Narashinodai, Funabashi, Chiba 274-8555, Japan.
  • 5. Pneumolabs UK Limited , Harrow, Middlesex HA1 3UJ, United Kingdom.
PMID: 26800309 DOI: 10.1021/acs.jmedchem.5b01029
Abstract

The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase Enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.