New potent and selective polyfluoroalkyl ketone inhibitors of GVIA calcium-independent phospholipase A
Group VIA calcium-independent phospholipase A₂ (GVIA iPLA₂) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA₂ inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of...
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Veröffentlicht in: | Bioorganic & medicinal chemistry 2013-09, Vol.21 (18), p.5823-5829 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Group VIA calcium-independent phospholipase A₂ (GVIA iPLA₂) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA₂ inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA₂ inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA₂ inhibitor ever reported with a XI(50) value of 0.0001, and with no significant inhibition against GIVA cPLA₂ or GV sPLA₂. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA₂, GIVA cPLA₂, and GV sPLA₂. |
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ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2013.07.010 |