Synthesis and cyclooxygenase inhibitory properties of novel (+) 2-(6-methoxy-2-naphthyl)propanoic acid (naproxene) derivatives.
Halomethylation of naproxene (1) occurs regioselectively in position 5 and subsequently--in situ or on treatment with silver nitrate--leads to naproxene-"dimers" with two naproxene units, 5,5'-connected through a ethenylene (3) and a methylene (4) bridge, respectively. Two of the new naproxene derivatives were screened for their cyclooxygenase inhibitory properties relative to naproxene. Both 5-chloromethyl naproxene (2) and 2-(5-((carboxyethyl)-2-methyloxynaphthyl)-6-methoxy-2-naphthyl)propanoic acid (4) were inactive in the concentration range of 0.1-10 mumole against both COX-1 and COX-2, indicating that bulky substituents in position 5 in naproxene are unfavourable for both COX-1 and COX-2 inhibition.
Abadi
A H
AH
Institute of Pharmacy, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
Laufer
S
S
Lehmann
J
J
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D009288:Naproxen / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009288:Naproxen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases