Aldehyde Oxidase Assay
The possibility that the compounds were cleared by aldehyde oxidase was discussed (GHI 214), compounds were sent to Pfizer for evaluation and data returned from Scott Obach's laboratory (along with comments from him), indicating that some Series 4 compounds were substrates for AO, and others are not.
For reference there is a very nice summary of AO over at Cambridge MedChem Consulting. There is also this 2019 perspective.
A second AO assay was done, discussed in issue #512. These compounds were similarly sent to Pfizer and upon data returning from Christine Orozco and Scott Obach's laboratory, were compared with the previous assay. This second assay allowed us to conclude that amides metabolised quickly and that imidazolopyridines are a metabolic risk compared to triazolopyrazine rings.
The details of each assay are summarised below.
