331978-37-1Relevant articles and documents
Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor
Trivedi-Parmar, Vinay,Robertson, Michael J.,Cisneros, José A.,Krimmer, Stefan G.,Jorgensen, William L.
, p. 1092 - 1097 (2018)
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is implicated in the regulation of inflammation, cell proliferation, and neurological disorders. MIF is also an enzyme that functions as a keto–enol tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which hydrogen bonds to Asn97 in the active site. Starting from a 113-μm docking hit, we report results of structure-based and computer-aided design that have provided substituted pyrazoles as phenol alternatives with potencies of 60–70 nm. Crystal structures of complexes of MIF with the pyrazoles highlight the contributions of hydrogen bonding with Lys32 and Asn97, and aryl–aryl interactions with Tyr36, Tyr95, and Phe113 to the binding.
CHEMICAL COMPOUNDS
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Page/Page column 15, (2008/06/13)
Compounds of formula (Ia) are found to be active in inhibiting replication of flaviviridae viruses (Ia), wherein R1 and R2 are the same or different and represent hydrogen, halogen, -L-O-R3, -L-O-L-A or -L-O-L′-A′, wherein each L is the same or different and represents a direct bond or a C1-C4 alkylene group; L′ represents a direct bond or a C2-C4 alkylene group; R3 represents hydrogen, C1-C4 alkyl or C1-C4 haloalkyl; A represents a 5- to 10-membered heterocyclyl group; and A′ represents a C6-C1 aryl group; wherein at least one of R1 and R2 is -L-O-R3, -L-O-L-A or -L-O-L′-A′.
