Submission Details
Molecule(s):
COC(=O)C(c1ccccc1Cl)N1CCc2sccc2C1
COC(=O)C(c1ccccc1Cl)N1CCC2SC(=O)C=C2C1
COC(=O)C(c1ccccc1Cl)N1CCC(S)/C(=C\C(=O)O)C1
COC(=O)C(c1ccccc1Cl)N1CCC(SC(C)=O)/C(=C\C(=O)O)C1
Design Rationale:
Further to my earlier suggestion of incorporating metabolically-unmasked covalent warheads*, I spoke with a clinical colleague Dr Tim Chevassut, @ Sussex who spoke about the problematic issues of cardiovascular disease and embolisms etc with covid-19 patients, which is becoming more rife. Treatment with e.g. aspirin, warfarin or PLAVIX might be a way of countering these other effects. Just imagine if plavix was effective in vivo not only vs platelet agregation but also a covalent warhead vs MPro? I suggest we look at plavix (probably in cells) and its metabolites: COC(C(C1C(Cl)=CC=CC=1)N1CC2C(SC(C=2)=O)CC1)=O should be react enough to engage the Cys?
Other Notes:
*See: https://discuss.postera.ai/t/round-2-is-finished-now-a-call-for-help/816/32 No fragment related.