کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1395603 | 1501132 | 2014 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core](/preview/png/1395603.png)
• Non-flat imidazolines were explored as selective cyclooxygenase-2 inhibitors.
• The compounds are novel as they are built around a polar non-lipophilic core.
• The potency of the best compound is comparable to that of celecoxib.
• The new lead series has a good oral bioavailability and efficacy in animal models.
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.
Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 84, 12 September 2014, Pages 160–172