کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1364126 | 981530 | 2009 | 5 صفحه PDF | دانلود رایگان |

The indole ring systems of the cytosolic phospholipase A2α (cPLA2α) inhibitor 1-[3-(4-octylphenoxy)-2-oxopropyl]indole-5-carboxylic acid (2) and the isomeric 6-carboxylic acid (3) were replaced by benzimidazole, benzotriazole and indazole scaffolds, respectively. The effect of the structural variations on cPLA2α inhibitory potency, metabolic stability and solubility was studied. The lead 2 and the indazole-5-carboxylic acid 28 were the metabolically most stable compounds in an assay with rat liver microsomes, while the benzimidazole-5-carboxylic acid derivative 13 possessed the best water solubility (22 μg/mL at pH 7.4). The indazole-5-carboxylic acid 28 revealed the highest cPLA2α inhibitory potency of the compounds in this series. With an IC50-value of 0.005 μM it was about sevenfold more active than the lead 2.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 8, 15 April 2009, Pages 2107–2111