Pyrazine Side Chain Modifications Others
Inherited data at the start of the project included the following, suggesting that O- or amide-based connectivity between pyrazine and side chain are superior.
In the inherited documentation at the start of the series was included the comment "The linker atom to the pyrazine ring is crucial (O>>C>N)." This was subsequently confirmed by Joanna Ubels (thesis), who synthesised the inactive N- and S-linked compounds OSM-S-188, OSM-S-190 and OSM-S-191. Edwin Tse synthesised the thioether, sulfoxide and sulfone analogs OSM-S-359, OSM-S-360 and OSM-S-361 which were inactive, though the analogous benzylic ether compounds (e.g. OSM-S-368) were also of reasonably low potency.
More recently an N-linked triazole analog (MMV693165, OSM-S-362) was discussed (a "reverse triazole"), synthesised and found to be inactive.
Substitution is required on the pyrazine ring - the following compounds were found to be inactive.
