Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition.

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Wilkerson WW, Copeland RA, Covington M, Trzaskos JM

Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition.

J Med Chem. 1995 Sep 29;38(20):3895-901.

PubMed ID
7562922 [ View in PubMed
]
Abstract

The antiinflammatory activity of a series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was previously shown by quantitative structure-activity relationship (QSAR) studies to be correlated with the molar refractivity and inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent. The present study demonstrates that much of the antiinflammatory activity of these pyrroles could be correlated with the inhibition of the inducible isoform of cyclooxygenase (COX2). Additional QSAR studies have been used to identify the molecular parameters necessary for maximizing COX2 inhibition while simultaneously minimizing the inhibition of constitutively expressed cyclooxygenase-1. Such an effort should facilitate the discovery and development of selective COX inhibitors that should lead to safer nonsteroidal antiinflammatory drugs.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Acetylsalicylic acidProstaglandin G/H synthase 2IC 50 (nM)18000000N/AN/ADetails
IbuprofenProstaglandin G/H synthase 2IC 50 (nM)8000N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2IC 50 (nM)180000N/AN/ADetails
NaproxenProstaglandin G/H synthase 2IC 50 (nM)9700N/AN/ADetails
PhenylbutazoneProstaglandin G/H synthase 2IC 50 (nM)284000N/AN/ADetails
PiroxicamProstaglandin G/H synthase 2IC 50 (nM)218000N/AN/ADetails