Synthesis of (2E)-3-{2-[(substituted benzyl)oxy]phenyl}acrylaldehydes as novel anti-inflammatory agents.
As part of our continuing effort for development of novel anti-inflammatory agents, the highly potential agent CCY1a, which we reported recently, was selected as lead compound to synthesize a series of its derivatives for evaluation. Most of the newly synthesized compounds exhibited superior inhibitory activity than both the lead compound and the positive control (trifluoperazine) toward fMLP-stimulated neutrophil superoxide formation. (2E)-3-[2-(Benzyloxy)-5-methoxyphenyl]-acrylaldehyde (31) was among the most potent with action mechanism different from CCY1a in that it does not act as cAMP-elevating agent but inhibits the increase in cellular Ca(2+) with greater potency.
Huang
Li-Jiau
LJ
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 40402, Taiwan, ROC. ljhuang@mail.cmu.edu.tw
Wang
Jih-Pyang
JP
Lai
Yu-Chi
YC
Kuo
Sheng-Chu
SC
D000447:Aldehydes / Q000138:chemical synthesis* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000447:Aldehydes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP