TY - JOUR
T1 - Computer-assisted rational design, synthesis, and bioassay of non-steroidal anti-inflammatory agents
AU - Girgis, Adel S.
AU - Tala, Srinivasa R.
AU - Oliferenko, Polina V.
AU - Oliferenko, Alexander A.
AU - Katritzky, Alan R.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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.
KW - 3D QSAR
KW - Anti-inflammatory activity
KW - Non-steroidal
KW - Rational design
UR - http://www.scopus.com/inward/record.url?scp=84858437350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858437350&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2011.11.034
DO - 10.1016/j.ejmech.2011.11.034
M3 - Article
C2 - 22365409
AN - SCOPUS:84858437350
VL - 50
SP - 1
EP - 8
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -