Medicinal chemical optimization of fluorescent pyrrole-based COX-2 probes

• DOI: 10.1016/j.tet.2022.132990
• Publication Date: 2022-08-28T15:20:13Z
• Authors: Sachin B. Wagh; Vladimir Maslivetc; James J. La Clair; Alexander Kornienko
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

Recent studies have demonstrated the ability of human prostaglandin-endoperoxide synthase 2 (COX-2) to guide the formation of fluorescent pyrroles through the Paal-Knorr reaction resulting in the discovery of a central motif. This initial discovery prompted further exploration of this motif for the design of COX-2 inhibitors through the modifications of the substituents on the pyrrole core. This effort led to the discovery of a set of pyrroles whose activity was comparable to Celecoxib, an orally prescribed nonsteroidal anti-inflammatory COX-2 inhibitor. Furthermore, structure-activity relationship (SAR) data, important for the discovery of COX-2 inhibitors, has been obtained.