Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors

Autor:	Paul F. Lambeth, Fiona S. Lucas, Richard Howard Green, Martin E. Swarbrick, Jeremy John Payne, Lee William Page, Malcolm Clive Carter, Paul John Beswick, Alexander J. Stevens, Sharon C Stratton, Neil Anthony Pegg, John Skidmore, Savvas Kleanthous, Alastair J. Stuart, Sue D. Collins, Sharon Bingham, John Andrew Corfield, Richard Stocker, Joanne O. Wiseman, C. David Hartley, Helen Susanne Price, Neil Mathews, Laura J. Chambers, Iain P. Chessell, Robert Gleave, Nick M. Clayton, Alan Naylor, C. Bountra
Rok vydání:	2008
Předmět:	Pyrimidine Stereochemistry Chemistry Pharmaceutical Clinical Biochemistry Pharmaceutical Science Ether Biochemistry Chemical synthesis Sulfone chemistry.chemical_compound Inhibitory Concentration 50 Mice Drug Discovery Animals Humans Sulfones Amines Molecular Biology chemistry.chemical_classification Inflammation Trifluoromethyl biology Cyclooxygenase 2 Inhibitors Molecular Structure Organic Chemistry Brain Neurodegenerative Diseases Rats Disease Models Animal Enzyme Pyrimidines chemistry Enzyme inhibitor Cyclooxygenase 2 Drug Design biology.protein Molecular Medicine Selectivity Ethers
Zdroj:	Bioorganicmedicinal chemistry letters. 19(15)
ISSN:	1464-3405
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dadff8d23a6fefccadd5166b5ed7fd16 https://pubmed.ncbi.nlm.nih.gov/19520573 Zobrazit plný text záznamu Full Text from ScienceDirect