The pyrrole moiety as a template for COX-1/COX-2 inhibitors.
Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a new class of COX-1/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX-1 and RIA for COX-2. Variation of the substitution pattern led to a series of active compounds which showed inhibition for COX-1 and COX-2. Structural requirements for the development of COX-1/COX-2 inhibitors are discussed.
Dannhardt
G
G
Johannes Gutenberg-University of Mainz, Institute of Pharmacy, Staudingerweg 5, D-55099, Mainz, Germany. dannhadt@mail.uni-mainz.de
Kiefer
W
W
Krämer
G
G
Maehrlein
S
S
Nowe
U
U
Fiebich
B
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002417:Cattle; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D008565:Membrane Proteins; D015394:Molecular Structure; D009000:Monocytes / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011758:Pyrroles; C110286:SC 57666; D013450:Sulfones; D013876:Thiophenes; D004008:Diclofenac; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin