Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors.
Swarbrick ME., Beswick PJ., Gleave RJ., Green RH., Bingham S., Bountra C., Carter MC., Chambers LJ., Chessell IP., Clayton NM., Collins SD., Corfield JA., Hartley CD., Kleanthous S., Lambeth PF., Lucas FS., Mathews N., Naylor A., Page LW., Payne JJ., Pegg NA., Price HS., Skidmore J., Stevens AJ., Stocker R., Stratton SC., Stuart AJ., Wiseman JO.
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.