Aminothiazoles: Promiscuity and Reactive metabolites

[bendndi]

A couple of thoughts on issues associated with 2-aminothiazoles

1) 2-aminothiazoles are known to undergo oxidative metabolism (epoxidation) to reactive metabolites; see this paper for an example. There are strategies to avoid this (substitution of both the 4 and 5 position; change to diaminothiazoles...), however this is certainly something to keep in mind as we move forward

2) 2-aminothiazoles come up everywhere, and this series is a frequent hitter in most DNDi screens. It's not necessarily an assay interference issue though (it's a frequent positive, not necessarily a frequent false positive), and there are indeed launched drugs with similar motifs, but again something to keep in mind.

[drc007]

@bendndi I agree, in which case if we can identify the mode of action alternative chemotypes might be attractive.