Philip A Macfaul

Summary

Affiliation: AstraZeneca R and D

Publications

  1. doi request reprint A simple in vitro assay for assessing the reactivity of nitrile containing compounds
    Philip A Macfaul
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 19:1136-8. 2009
  2. doi request reprint Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and design of isosteres yielding orally available cathepsin K inhibitors
    James J Crawford
    AstraZeneca R and D, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    J Med Chem 55:8827-37. 2012
  3. doi request reprint Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition
    Alexander G Dossetter
    AstraZeneca R and D, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
    Bioorg Med Chem Lett 22:5563-8. 2012
  4. doi request reprint Conformational restriction in a series of GPR119 agonists: differences in pharmacology between mouse and human
    James S Scott
    Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 23:3175-9. 2013
  5. doi request reprint Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
    James S Scott
    Innovative Medicines Unit, AstraZeneca Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, U K
    J Med Chem 57:8984-98. 2014
  6. doi request reprint Novel inhibitors of the alphavbeta3 integrin--lead identification strategy
    David Elliot
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 19:4832-5. 2009
  7. doi request reprint (1R,2R)-N-(1-cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): a potent and highly selective cathepsin K inhibitor for the treatment of osteoarthritis
    Alexander G Dossetter
    AstraZeneca R and D, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
    J Med Chem 55:6363-74. 2012
  8. doi request reprint Selective non zinc binding inhibitors of MMP13
    Chris De Savi
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 21:4215-9. 2011
  9. doi request reprint 5-Aminopyrimidin-2-ylnitriles as cathepsin K inhibitors
    Andrew D Morley
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 19:1658-61. 2009
  10. pmc Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat
    James S Scott
    Oncology iMED, AstraZeneca, Mereside, Alderley Park, Macclesfield, SK10 4TG, U K
    ACS Med Chem Lett 7:94-9. 2016

Collaborators

  • Stefan Steinbacher
  • James J Crawford
  • Darren McKerrecher
  • Alexander G Dossetter
  • Peter W Kenny
  • Jonathan Bowyer
  • Andrew G Leach
  • Richard A Norman
  • Bryan Roberts
  • Alan M Birch
  • Holger Steuber
  • Klaus Maskos
  • Nicola M Heron
  • James S Scott
  • Andrew D Morley
  • Katy J Brocklehurst
  • David S Clarke
  • Paul Schofield
  • Hayley S Brown
  • David Laber
  • Per H Svensson
  • Julian A Hudson
  • Kristin Goldberg
  • Anne Ertan
  • Joanne Teague
  • Sam D Groombridge
  • Chris De Savi
  • Stefan Gerhardt
  • David Buttar
  • Attilla Ting
  • Christine M Wood
  • Neil Rankine
  • Ken Page
  • David Elliot
  • THOMAS MOSS
  • Helen Gingell
  • Jennifer H Pink
  • Sébastien L Degorce
  • Andrew Bailey
  • Robert D M Davies
  • Peter D Smith
  • Alfred A Rabow
  • Alison Easter
  • Elizabeth A Martin
  • Stefan Kavanagh
  • Suzanne S Bowker
  • Helen Coe
  • Roger J Butlin
  • Adrian Pickup
  • Anders Broo
  • Pernilla Sörme
  • Ojvind Davidsson
  • Kostas Karabelas
  • Sarah V Baker
  • David Hargreaves
  • Michael James
  • Galith Karoutchi
  • David Ryan
  • Stephen J Norris
  • Ian Nash
  • Gordon Hamlin
  • Kin Tam
  • Alleyn Plowright
  • Paul Whittamore
  • Scott D Phillips
  • Nicola Colclough
  • Brenda Burton
  • Peter Newham
  • Soraya S Porres
  • Lyn Rosenbrier Ribeiro
  • Keith Oldham
  • Eleanor Henshaw
  • Stuart Ward
  • Tina J Wilkinson
  • Robert A Heald
  • Paul Sharpe
  • Julia Mullett
  • Phil Smith

Detail Information

Publications12

  1. doi request reprint A simple in vitro assay for assessing the reactivity of nitrile containing compounds
    Philip A Macfaul
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 19:1136-8. 2009
    ..Studies have indicated that, when benchmarked with selected compounds, the reaction of the nitriles with glutathione can provide a useful tool for deciding whether or not to progress compounds in the absence of radiolabelling studies...
  2. doi request reprint Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and design of isosteres yielding orally available cathepsin K inhibitors
    James J Crawford
    AstraZeneca R and D, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    J Med Chem 55:8827-37. 2012
    ..Through metabolite identification studies, a reactive metabolite risk was identified with this motif. Subsequent structure-based design of isoteres culminated in the discovery of an optimized and balanced inhibitor (indazole, 38)...
  3. doi request reprint Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition
    Alexander G Dossetter
    AstraZeneca R and D, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
    Bioorg Med Chem Lett 22:5563-8. 2012
    ....
  4. doi request reprint Conformational restriction in a series of GPR119 agonists: differences in pharmacology between mouse and human
    James S Scott
    Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 23:3175-9. 2013
    ..This highlights the large effects on GPCR phamacology that can result from small structural changes in the ligand, together with inter-species differences between receptors...
  5. doi request reprint Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
    James S Scott
    Innovative Medicines Unit, AstraZeneca Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, U K
    J Med Chem 57:8984-98. 2014
    ..Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119. ..
  6. doi request reprint Novel inhibitors of the alphavbeta3 integrin--lead identification strategy
    David Elliot
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 19:4832-5. 2009
    ..A novel approach to inhibition of the alphavbeta3 integrin is described, which uses compounds designed to generate nM potency without using the arginine binding site...
  7. doi request reprint (1R,2R)-N-(1-cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): a potent and highly selective cathepsin K inhibitor for the treatment of osteoarthritis
    Alexander G Dossetter
    AstraZeneca R and D, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
    J Med Chem 55:6363-74. 2012
    ..Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile...
  8. doi request reprint Selective non zinc binding inhibitors of MMP13
    Chris De Savi
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 21:4215-9. 2011
    ..The binding mode of the series has been solved by co-crystallisation and demonstrates an interesting mode of inhibition without interaction with the catalytic zinc atom...
  9. doi request reprint 5-Aminopyrimidin-2-ylnitriles as cathepsin K inhibitors
    Andrew D Morley
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Bioorg Med Chem Lett 19:1658-61. 2009
    ..A series of pyrimidine nitrile inhibitors of Cathepsin K with reduced glutathione reactivity has been identified and Molecular Core Matching (MoCoM) has been used to quantify the effect of an amino substituent at C5...
  10. pmc Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat
    James S Scott
    Oncology iMED, AstraZeneca, Mereside, Alderley Park, Macclesfield, SK10 4TG, U K
    ACS Med Chem Lett 7:94-9. 2016
    ..The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat. ..
  11. doi request reprint Use of small-molecule crystal structures to address solubility in a novel series of G protein coupled receptor 119 agonists: optimization of a lead and in vivo evaluation
    James S Scott
    Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    J Med Chem 55:5361-79. 2012
    ..The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism...
  12. doi request reprint A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions
    David Buttar
    AstraZeneca, Alderley Park, Macclesfield, Cheshire SK104TG, England, United Kingdom
    Bioorg Med Chem 18:7486-96. 2010
    ..The crystallography results support the findings from the fluorescence displacement assay. The results indicate that drug binding to subdomain IB might also be important location for certain compounds...