Computer-assisted rational design, synthesis, and bioassay of non-steroidal anti-inflammatory agents

作者：Girgis Adel S; Tala Srinivasa R; Oliferenko Polina V; Oliferenko Alexander A; Katritzky Alan R^*

来源：European Journal of Medicinal Chemistry, 2012, 50: 1-8.

DOI：10.1016/j.ejmech.2011.11.034

• Anti-inflammatory activity
• Non-steroidal
• Rational design
• 3D QSAR

A focused dataset of previously synthesized and tested [1,2,4]-triazolo[1,5-a]pyridines and pyridine-3-carboxylates was studied by Molecular Field Topology Analysis (MFTA) to identify steric and electronic determinants of anti-inflammatory activity useful for the design and synthesis of new anti-inflammatory agents. Rational design based on the MFTA model identified eleven novel pyridine-3-carboxylates (2a-e and 3a-f) as promising. After synthesis and screening, three of (2a, 2c, 3a) revealed potent anti-inflammatory activity exceeding that of indomethacin, the reference inhibitor for artificially induced edema in rats.

• 出版日期2012-4