Paul D Leeson
Affiliation: AstraZeneca R and D
- The influence of drug-like concepts on decision-making in medicinal chemistryPaul D Leeson
AstraZeneca R and D Charnwood, Bakewell Road, Loughborough LE15 5RH, UK
Nat Rev Drug Discov 6:881-90. 2007..Tackling the threat of compound-related toxicological attrition needs to move to the mainstream of medicinal chemistry decision-making...
- Drug-like properties: guiding principles for design - or chemical prejudice?Paul D Leeson
Department of Medicinal Chemistry, AstraZeneca R and D Charnwood, Bakewell Road, Loughborough, Leics, UK LE11 5RH Electronic
Drug Discov Today Technol 1:189-95. 2004..Novel library synthesis, creating new chemical classes to address intellectual property, toxicity issues, and less chemically tractable targets, though considered risky, is warranted.: ..
- Time-related differences in the physical property profiles of oral drugsPaul D Leeson
Department of Medicinal Chemistry, AstraZeneca R and D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK
J Med Chem 47:6338-48. 2004..The results suggest that the balance between polar and nonpolar drug properties is an important, unchanging feature of oral drug molecules...
- A comparison of physiochemical property profiles of development and marketed oral drugsMark C Wenlock
Department of Physical and Metabolic Science, AstraZeneca R and D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, United Kingdom
J Med Chem 46:1250-6. 2003..It is also clear that the most lipophilic compounds are being discontinued from development...
- The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS)David R Cheshire
Department of Chemistry, AstraZeneca Charnwood, Bakewell Road, Loughborough LE11 5RH, United Kingdom
Bioorg Med Chem Lett 21:2468-71. 2011..By careful analysis of experimental X-ray ligand crystallographic protein data across several inhibitor series we have discovered a novel, potent and selective series of iNOS inhibitors exemplified by compound 8...
- Lessons learned from candidate drug attritionJames R Empfield
AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19850, USA
IDrugs 13:869-73. 2010..Separating the key scientific experiment--proof-of-concept clinical trials in humans--from commercial development imperatives is a necessary step for the industry...
- The influence of the 'organizational factor' on compound quality in drug discoveryPaul D Leeson
AstraZeneca R and D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK
Nat Rev Drug Discov 10:749-65. 2011..On the basis of our analysis, we conclude that a substantial sector of the pharmaceutical industry has not modified its drug design practices and is still producing compounds with suboptimal physicochemical profiles...
- From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosisBrian Springthorpe
AstraZeneca R and D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK
Bioorg Med Chem Lett 17:6013-8. 2007..The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae...
- Strategies to improve in vivo toxicology outcomes for basic candidate drug moleculesTim Luker
AstraZeneca R and D, Medicinal Chemistry, Charnwood, Loughborough, Leicestershire LE11 5RH, UK
Bioorg Med Chem Lett 21:5673-9. 2011..The themes within this work provide additional guidance for medicinal design chemists and complement other literature property guidelines...
- 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1Robert W Carling
Department of Medicinal Chemistry, The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
J Med Chem 47:1807-22. 2004....