Critical modifications of the ISO-1 scaffold improve its potent inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity.
Based on the scaffold of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of the proinflammatory cytokine MIF, two critical modifications and chiral resolution have significantly improved the potency of the inhibition. Compound (R)-17 is 20-fold more potent than ISO-1 and inhibits MIF tautomerase activity with an IC(50) of 550 nM.
Cheng
Kai Fan
KF
Department of Medicinal Chemistry, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA.
Al-Abed
Yousef
Y