Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues

Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies

“…The enhancement of MAO-B inhibition potencies by halogen substitution has been previously described. For example, chlorine and bromine substitution on the benzyloxy phenyl ring of a series of 8-benzyloxycaffeines enhances the MAO-B inhibition potencies 20 and 22-fold, respectively [34].…”

Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues

“…21 For example, 8-(3-chlorobenzyloxy)caffeine (6) (Fig. 3) inhibits recombinant human MAO-B with a K i value of 0.036 lM, approximately 10 5 -fold more potently than caffeine.…”

“…18 Among the C5-and C6-substituents chosen for this study was the benzyloxy side chain which has been shown to enhance the binding affinity of caffeine to the active site of both MAO-A and MAO-B. 21 Other substituents considered in this study include the phenoxy, 2-phenylethyl, 4-phenylbutyl, phenyl and 4-chlorophenoxy groups. We have also examined the importance of the isatin moiety for binding to MAO-A and MAO-B by comparing the inhibition potencies of the C5-and C6-substituted isatins with those of the corresponding aniline analogues.…”

Halogen…π Interactions as Important Contributors to Binding Affinity in Medicinal Chemistry

“…π interaction with Tyr100 (distance 4.1Å, height 3.9Å) and was identified as a critical feature for an efficient MDM2/p53 inhibitor. A marked dependence of the activity on the 3-chlorophenyl and 3-bromophenyl substitution was also observed in a series of 8-benzyloxycaffeine analogues as monoamine oxidase B (MAO B) inhibitors as reported by Strydom et al [136], Table 8.4. The corresponding nonsubstituted phenyl ring in 12a or the 3-methylphenyl ring 12d were 20-fold and sixfold less active than the corresponding halogenated analogues 12b or 12c.…”