| Autor: |
Schwarzkopf, Julian, Sundermann, Tom, Arnsmann, Martina, Hanekamp, Walburga, Fabian, Jörg, Heidemann, Jan, Pott, Anna, Bettenworth, Dominik, Lehr, Matthias |
| Zdroj: |
Medicinal Chemistry Research; Dec2014, Vol. 23 Issue 12, p5250-5262, 13p |
| Abstrakt: |
Cytosolic phospholipase Aα is a serine hydrolase involved in the generation of pro-inflammatory lipid mediators. Here, we describe structure-activity relationship studies on a series of carbamate-substituted indazole-5-carboxylic acid inhibitors of this enzyme. Bioavailability experiments in mice with 1-(3-(4-butylphenoxy)-2-{[(ethylthio)carbonyl]amino}propyl)indazole-5-carboxylic acid ( 14) revealed a high rate of glucuronidation and biliary excretion of this compound. Replacement of the rigid aromatic carboxylic acid system by a more flexible aliphatic one led to substances with a significantly increased in vitro stability against metabolic glucuronidation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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