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.
MeSH terms
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Amines / chemical synthesis*
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Amines / pharmacology
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Animals
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Brain / drug effects
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Brain / metabolism
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Chemistry, Pharmaceutical / methods
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 Inhibitors / chemical synthesis*
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Cyclooxygenase 2 Inhibitors / pharmacology
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Disease Models, Animal
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Drug Design
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Ethers / chemical synthesis*
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Ethers / pharmacology
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Humans
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Inflammation
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Inhibitory Concentration 50
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Mice
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Molecular Structure
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Neurodegenerative Diseases / drug therapy
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology
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Rats
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Sulfones / chemical synthesis*
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Sulfones / pharmacology
Substances
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Amines
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Cyclooxygenase 2 Inhibitors
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Ethers
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Pyrimidines
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Sulfones
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Cyclooxygenase 2