1621586-62-6Relevant articles and documents
Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core
Sarnpitak, Pakornwit,Mujumdar, Prashant,Morisseau, Christophe,Hwang, Sung Hee,Hammock, Bruce,Iurchenko, Vladimir,Zozulya, Sergey,Gavalas, Antonis,Geronikaki, Athina,Ivanenkov, Yan,Krasavin, Mikhail
, p. 160 - 172 (2014/07/22)
A novel series of compounds containing a polar, non-flat 2-imidazoline core was designed based on the SAR information available for aromatic azole cyclooxygenase-2 inhibitors. While the majority of the compounds prepared using an earlier developed imidazoline N-arylation methodology turned out to be inferior to the known COX-2 inhibitors, one lead compound displayed potency (300 nM) comparable to clinically used Celecoxib and was shown to be more selective. The series represents the first example of selective COX-2 inhibitors built around a distinctly polar core, contradicting an earlier accepted view that a lipophilic scaffold is required for high inhibitor potency. The lead compound demonstrated very good oral bioavailability in mice, slow metabolic degradation, modest distribution into the brain and a remarkable anti-inflammatory efficacy in carrageenan-induced mouse paw edema model. A foundation has therefore been laid for a chemically novel series of COX-2 inhibitors that has a potential for diverse therapeutic applications in inflammatory disease area.
