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Your search keyword '"Tim Longstaff"' showing total 2 results
Start Over Author "Tim Longstaff" Topic amides
2 results on '"Tim Longstaff"'

1. Kinase array design, back to front: Biaryl amides

Author

Paul Bamborough, Ian Robert Baldwin, Jo Quinn, Don O. Somers, Christopher J. Mooney, Claudine Haslam, Shila Patel, Suchete S. Hunjan, and Tim Longstaff

Subjects
Models, Molecular, Purine, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Crystallography, X-Ray, Biochemistry, Chemical synthesis, Mitogen-Activated Protein Kinase 14, Heterocyclic Compounds, 1-Ring, Inhibitory Concentration 50, Structure-Activity Relationship, chemistry.chemical_compound, Adenosine Triphosphate, Amide, Drug Discovery, Animals, Combinatorial Chemistry Techniques, Structure–activity relationship, Transferase, Protein Kinase Inhibitors, Molecular Biology, Molecular Structure, biology, Chemistry, Kinase, Organic Chemistry, Amides, Rats, Mitogen-activated protein kinase, biology.protein, Molecular Medicine, Signal transduction
Abstract

New kinase inhibitors can be found by synthesis of targeted arrays of compounds designed using system-based knowledge as well as through screening focused or diverse compounds. Most array strategies aim to add functionality to a fragment that binds in the purine subpocket of the ATP-site. Here, an alternative pharmacophore-guided array approach is described which set out to discover novel purine subpocket-binding groups. Results are shown for p38alpha and cFMS kinase, for which multiple distinct series with nanomolar potency were discovered. Some of the compounds showed potency in cell-based assays and good pharmacokinetic properties.

Published
2008

2. Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR

Author

Richard Martyn Angell, David W. Brown, Katherine Louise Jones, Smith Kathryn Jane, Ann Louise Walker, Penny A. Smee, Tim Longstaff, Paul Bamborough, Tony D. Angell, Stuart G. Cockerill, Chris D. Edwards, Don O. Somers, Murray J. B. Brown, Jacky B. Buckton, and Malcolm Willson

Subjects
Models, Molecular, Stereochemistry, p38 mitogen-activated protein kinases, Clinical Biochemistry, Biphenyl derivatives, Molecular Conformation, Pharmaceutical Science, Administration, Oral, Non-specific serine/threonine protein kinase, Crystallography, X-Ray, Biochemistry, p38 Mitogen-Activated Protein Kinases, Piperazines, chemistry.chemical_compound, Structure-Activity Relationship, In vivo, Amide, Drug Discovery, Animals, Molecular Biology, Protein Kinase Inhibitors, chemistry.chemical_classification, Biphenyl, Oxadiazoles, Organic Chemistry, Biphenyl Compounds, Amides, Arthritis, Experimental, Rats, Enzyme, chemistry, Molecular Medicine, Protein Binding
Abstract

The biphenyl amides are a novel series of p38 MAP kinase inhibitors. Structure–activity relationships of the series against p38α are discussed with reference to the X-ray crystal structure of an example. The series was optimised rapidly to a compound showing oral activity in an in vivo disease model.

Published
2007

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