Synthesis of novel pyridazino[1,6-a]indole-2,4(1H,3H)-dione and pyridazino[1,6-a]indol-2(1H)-one via intramolecular electrophilic aromatic substitution

Cyclization of judiciously substituted N-aminoindole species provides a convenient synthetic route to ABE building block types I and II as tricyclic skeleton commonly found in the motif of indolic alkaloids. The approach consists in obtaining a tricyclic derivative by using an intramolecular electrophilic aromatic substitution with a simple acid catalyst. A terminal capping group, such as the pyridazinoindolone scaffold, is bulky enough to preferentially bind in the cavity of histone deacetylase 7 (HDAC7) without affecting HDAC1, offering a clue to selective inhibition of class IIa versus class I HDAC enzymes.