Synthesis, antiproliferative, and antiplatelet activities of oxime- and amide-containing quinolin-2(1H)-one derivatives
| Autor: | I-Li Chen, Chang-Hui Liao, Ken-Ming Chang, Chang-Ling Miaw, Jih Jung Chen, Tai-Chi Wang |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Platelet Aggregation
Stereochemistry medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide Biochemistry Chemical synthesis Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Amide Oximes Drug Discovery medicine Humans Schmidt reaction Molecular Biology Cell Proliferation Bicyclic molecule Organic Chemistry Oxime Amides chemistry Quinolines Lactam Molecular Medicine Acetamide |
| Zdroj: | Bioorganic & Medicinal Chemistry. 15:6527-6534 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2007.07.007 |
| Popis: | Certain oxime- and amide-containing quinolin-2(1H)-one derivatives were synthesized and evaluated for their antiproliferative and antiplatelet activities. These compounds were synthesized via alkylation of hydroxyl precursors followed by the reaction with NH(2)OH or NaN(3) (Schmidt reaction). The preliminary assays indicated that amide derivatives are either weakly active or inactive while the oxime counterparts exhibited potent inhibitory activities against platelet aggregation induced by collagen, AA (arachidonic acid), and U46619 (the stable thromboxan A(2) receptor agonist). Among them, (Z)-6-[2-(4-methoxyphenyl)-2-hydroxyiminoethoxy]quinolin-2(1H)-one (7c) was the most active against AA induced platelet aggregation with an IC(50) of 0.58microM and was inactive against cell proliferation. For the inhibition of U46619 induced aggregation, 7a and 8a-c exhibited very potent activities with IC(50) values in a range between 0.54 and 0.74microM. For the antiproliferative evaluation, N-(biphenyl-4-yl)-2-(2-oxo-1,2-dihydroquinolin-7-yloxy)acetamide (11d) was the most potent with GI(50) values of |
| Databáze: | OpenAIRE |
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