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 it was noted that "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"), synthesized and found to be inactive.
Substitution is required on the pyrazine ring - the following compounds were found to be inactive.
