Significant SAR has been done looking at 2-aminothiazoles as anti-tubercular agents. We can potentially use this to inform our SAR approach for mycetoma.
In 2016, Kesicki et al. determined that the right-hand "thiourea derived" ring (referred to in paper as "C-2 position") requires a pyridine for activity, which mirrors our results so far. They found that multiple linkers in this area maintained activity, including amides and urea instead of amines. Few conclusions were made about the "bromoketone derived" or "C-4" position. All isosteric replacements of the thiazole core resulted in loss of activity.
Pieroni et al. explored moving substituents around the thiourea-derived ring, and found that moving from para -> ortho dramatically reduced activity with chlorine, but not methyl. This doesn't really correspond with our findings for mycetoma.
Meissner et al. considered many analogues including amide linked versions and inverted amides. They describe methods of making different isosteric cores. Compound 68 is the pyridine analogue with amide link (no methyl).
Significant SAR has been done looking at 2-aminothiazoles as anti-tubercular agents. We can potentially use this to inform our SAR approach for mycetoma.
In 2016, Kesicki et al. determined that the right-hand "thiourea derived" ring (referred to in paper as "C-2 position") requires a pyridine for activity, which mirrors our results so far. They found that multiple linkers in this area maintained activity, including amides and urea instead of amines. Few conclusions were made about the "bromoketone derived" or "C-4" position. All isosteric replacements of the thiazole core resulted in loss of activity.
Pieroni et al. explored moving substituents around the thiourea-derived ring, and found that moving from para -> ortho dramatically reduced activity with chlorine, but not methyl. This doesn't really correspond with our findings for mycetoma.
Meissner et al. considered many analogues including amide linked versions and inverted amides. They describe methods of making different isosteric cores. Compound 68 is the pyridine analogue with amide link (no methyl).