Non‐steroidal Anti‐inflammatory Agents, Part 24[1] Pyrrolidino Enaminones as Models to Mimic Arachidonic Acid
- 1 January 1997
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 330 (3) , 74-82
- https://doi.org/10.1002/ardp.19973300307
Abstract
The pyrrolidino enaminones, with the carboxylic acid chain fixed at the nitrogen, inhibit cyclooxygenase more potently or selectively than 5-lipoxygenase. According to the structure-activity relationships discussed the potency depends significantly on the chain length of the carboxylic acid, the substitution pattern of the heterocyclic moiety and of the phenyl group. Compound 4c is the most efficient inhibitor of cyclooxygenase. For the binding profile the unfolded conformation of arachidonic acid and the energy-minimized conformations of flurbiprofen, diclofenac, ML 3000, and lead compound 4a were compared. In addition to known structural features, similar distances of the carboxylic acid function and the phenyl residue were found as hypothesized to explain the interaction with the active sites of the enzyme. The inhibition of cyclooxygenase was determined in a bovine thrombocyte intact cell assay and that of 5-lipoxygenase using intact bovine PMNLs.Keywords
This publication has 19 references indexed in Scilit:
- Enaminones as SynthonesPublished by Wiley ,2004
- Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouseCell, 1995
- Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase IINature, 1995
- Synthesis and Anticonvulsant Activity of Enaminones. 3. Investigations on 4'-, 3'-, and 2'-Substituted and Polysubstituted Anilino Compounds, Sodium Channel Binding Studies, and Toxicity Evaluations1,2Journal of Medicinal Chemistry, 1995
- The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1Nature, 1994
- ω-Aminoalkylheterocycles - Actual Aspects of the Chemistry of Histamine AnaloguesSynlett, 1994
- In-vitro Evaluation of 5-Lipoxygenase and Cyclo-oxygenase Inhibitors using Bovine Neutrophils and Platelets and HPLCJournal of Pharmacy and Pharmacology, 1992
- Synthesis and quantitative structure-activity relationships of diclofenac analogsJournal of Medicinal Chemistry, 1990
- Regiospezifität und Regioselektivität der Alkylierung, Acylierung, Sulfenylierung und Sulfonylierung von Enaminonen der PyrrolidinreiheArchiv der Pharmazie, 1988
- Synthesis of the carbapenam system from glutamic acid and acetoacetic acid derivativesThe Journal of Organic Chemistry, 1983