A set of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives 
(16â32) showing anti-inflammatory activity was analyzed using a 
three-dimensional qualitative structure-selectivity relationship (3D QSSR) 
method. The CatalystHipHop approach was used to generate a pharmacophore model 
for cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active 
inhibitors (1â15). The degree of fitting of the test set compounds (16â32) to 
the generated hypothetical model revealed a qualitative measure of the more or 
less selective COX-2 inhibition of these compounds. The results indicate that 
most derivatives (16, 18, 20â25, and 30â32) are able to effectively satisfy the 
proposed pharmacophore geometry using energy accessible conformers (E(conf) < 20 
kcal/mol). In addition, the triazole derivatives (16â32) were docked into COX-1 
and COX-2 X-ray structures, using the program GOLD. Based on the docking results 
it is suggested that several of these novel triazole derivatives are active COX 
inhibitors with a significant preference for COX-2. In principle, this work 
presents an interesting, comprehensive approach to theoretically predict the 
mode of action of compounds that showed anti-inflammatory activity in an in vivo 
model.