Synthesis and biological evaluation of novel pyrazole compounds.
A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d]pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2.
Youssef
Amal M
AM
Department of Chemistry, University of British Columbia Okanagan, Kelowna, BC, Canada.
Neeland
Edward G
EG
Villanueva
Erika B
EB
White
M Sydney
MS
El-Ashmawy
Ibrahim M
IM
Patrick
Brian
B
Klegeris
Andis
A
Abd-El-Aziz
Alaa S
AS
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D000068579:Celecoxib; D002460:Cell Line; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013449:Sulfonamides / Q000737:chemistry / Q000633:toxicity
C553153:2-methylbenzylamino 2-oxo-N-(4-cyano-1-phenyl-1H-pyrazol-5-yl)acetamide; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; C553154:N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide; D011720:Pyrazoles; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib