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John Liddle,
Paul Bamborough,
Michael D Barker,
Sebastien Campos,
Chun-Wa Chung,
Rick P C Cousins,
Paul Faulder,
Michelle L Heathcote,
Heather Hobbs,
Duncan S Holmes, [......],
Cesar Ramirez-Molina,
Mary A Morse,
Ruth Osborn, Jeremy J Payne,
John M Pritchard,
William L Rumsey,
Daniel T Tape,
Giorgia Vicentini,
Caroline Whitworth,
Rick A Williamson
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ABSTRACT: The lead optimization of a series of potent azaindole IKK2 inhibitors is described. Optimization of the human whole blood activity and selectivity over IKK1 in parallel led to the discovery of 16, a potent and selective IKK2 inhibitor showing good efficacy in a rat model of neutrophil activation.
Bioorganic & medicinal chemistry letters 06/2012; 22(16):5222-6. · 2.65 Impact Factor
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John Liddle,
Paul Bamborough,
Michael D Barker,
Sebastien Campos,
Rick P C Cousins,
Geoffrey J Cutler,
Heather Hobbs,
Duncan S Holmes,
Chris Ioannou,
Geoff W Mellor,
Mary A Morse, Jeremy J Payne,
John M Pritchard,
Kathryn J Smith,
Daniel T Tape,
Caroline Whitworth,
Richard A Williamson
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ABSTRACT: The synthesis and SAR of a novel series of IKK2 inhibitors are described. Modification around the hinge binding region of the 7-azaindole led to a series of potent and selective inhibitors with good cellular activity.
Bioorganic & medicinal chemistry letters 04/2009; 19(9):2504-8. · 2.65 Impact Factor
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Martin E Swarbrick,
Paul J Beswick,
Robert J Gleave,
Richard H Green,
Sharon Bingham,
Chas Bountra,
Malcolm C Carter,
Laura J Chambers,
Iain P Chessell,
Nick M Clayton, [......],
Lee W Page, Jeremy J Payne,
Neil A Pegg,
Helen S Price,
John Skidmore,
Alexander J Stevens,
Richard Stocker,
Sharon C Stratton,
Alastair J Stuart,
Joanne O Wiseman
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ABSTRACT: A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (47), a member of the 2-pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic profile, high brain penetration and good efficacy in rat models of hypersensitivity.
Bioorganic & medicinal chemistry letters 03/2009; 19(15):4504-8. · 2.65 Impact Factor
