Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity

Optically active helicene derivatives inhibit the activity on histamine N -methyl transferase (HNMT). Specifically, methyl ( P )-1,12-dimethylbenzo[ c ]phenanthrene-8-carboxylate with 6-iodo and 5-trifluoromethanesulfonyloxy groups inhibits HNMT activity on the μM order of IC 50 . Chirality is important, and ( M )-isomers exhibits substantially reduced activity. The 6-iodo group is also essential, which suggests the involvement of halogen bonds in protein binding. Substituents on the sulfonate moiety also affect the inhibitory activity.