The "Mannich Phenol" motif that is potentially problematic in the 3301 series is mentioned in
https://pubs.acs.org/doi/10.1021/acschembio.7b00903
and
https://pubs.rsc.org/en/content/articlehtml/2017/ra/c7ra06736d
Neither is an exact match. The flexibility of the motifs shown implies there is the possibility of a need for chelation if the motif is to be a problem. We don't have that, do we?
The second paper above does say that the PAIN effect disappears when the OH is methylated, and I see that that is a current synthetic target, which makes a lot of sense.
The papers don't provide a reason why the motif is an issue, but just show that they show up slightly more freqently than they ought, based on chance.
The "Mannich Phenol" motif that is potentially problematic in the 3301 series is mentioned in
https://pubs.acs.org/doi/10.1021/acschembio.7b00903
and
https://pubs.rsc.org/en/content/articlehtml/2017/ra/c7ra06736d
Neither is an exact match. The flexibility of the motifs shown implies there is the possibility of a need for chelation if the motif is to be a problem. We don't have that, do we?
The second paper above does say that the PAIN effect disappears when the OH is methylated, and I see that that is a current synthetic target, which makes a lot of sense.
The papers don't provide a reason why the motif is an issue, but just show that they show up slightly more freqently than they ought, based on chance.