Synthesis of Metabolites and Related Compounds of 3-Isobutyryl-2-isopropylpyrazolo[1, 5-α]pyridine (Ibudilast). I. Metabolites of Alkyl Side Chains

抄録

3-Isobutyryl-2-isopropylpyrazolo[1, 5-α]pyridine (ibudilast) has a large number of metabolites. In order to unequivocally establish the true identity of these metabolites, we prepared a series of authentic reference compounds, namely novel pyrazolo[1, 5-α]pyridine derivatives with mono- and dihydroxylated alkyl side chains and carboxylated alkyl side chains. These results lead to the conclusion that reactions at the 3-position of pyrazolo[1, 5-α]pyridine are governed by the electron-donating effect and the weak basicity of bridge-head nitrogen. On the basis of these results we were able to establish a method of functional group introduction to the alkyl side chains of pyrazolo[1, 5-α]pyridine.