SYNTHESIS OF METABOLITES AND RELATED-COMPOUNDS OF 3-ISOBUTYRYL-2-ISOPROPYLPYRAZOLO[1,5-A]PYRIDINE (IBUDILAST) .1. METABOLITES OF ALKYL SIDE-CHAINS

3-Isobutyryl-2-isopropylpyrazolo[1,5-a]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-a]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-a]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-a]pyridine.