Synthesis of Metabolites and Related Compounds of 3-Isobutyryl-2-isopropylpyrazolo[1, 5-α]pyridine (Ibudilast). II. Metabolites of Pyridine Ring

抄録

Novel 6-hydroxylated or methanesulfonylated pyrazolo[1, 5-α]pyridine derivatives as an authentic reference of metabolites for 3-isobutyryl-2-isopropylpyrazolo[1, 5-α]pyridine (ibudilast) were prepared by the method of substitution with Br⁺ on the pyridine ring and subsequent displacement of Br with MeO^- or MeS^-. For this reason, we investigated the orientation of halogenation on the pyridine ring of pyrazolo[1, 5-α]pyridine. The reactivity of the pyridine ring was at the 6-position, folowed by the 4-position. We supposed that this finding comes from the electron-donating resonance effect of bridge-head nitrogen. These experimental results were in good agreement with the results of atomic electron densities, but a clear difference was not obtained in those of the Frontier orbitals.