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

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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

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

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4504-8. doi: 10.1016/j.bmcl.2009.02.085. Epub 2009 Feb 26.

PubMed ID
19520573 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)68N/AN/ADetails
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)336N/AN/ADetails
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)63N/AN/ADetails
EtoricoxibProstaglandin G/H synthase 2IC 50 (nM)347N/AN/ADetails
EtoricoxibProstaglandin G/H synthase 2IC 50 (nM)554N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)32N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)260N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)107N/AN/ADetails
ValdecoxibProstaglandin G/H synthase 2IC 50 (nM)183N/AN/ADetails