2‐aminothiazoles as antitubercular agents

2-aminothiazoles are a widely used motif in medicinal chemistry (ref 1).

SAR

Need a 2-pyridyl substituent at position 4 of the thiazole ring ref 2, 2014.

• para > meta > ortho
• doesn't tolerate changes to lefthand pyridine ring
• amide linker superior to amine, urea or acylthiourea

Note that our preliminary results support this e.g. MYOS538, with F in the para position, has slightly better activity than MYOS537 with F in the meta position. However these are substituted pyridyl rings, not phenyl.

Ref 3 (2016)

• again confirms that 2-pyridyl at C-4 of thioazole is required
• some flexibility in C-2 of ring e.g. amine linker, amide linker both have activity
• activity and cytotoxicity are closely linked but amide and urea linkers give some selectivity
• iron chelation does not appear to be MOA