Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/PET-UNK-a692de38
This submission is related to PET-UNK-5ecb6237 and NIR-WEI-75ed5c39 and I’ll mention @londonir @mc-robinson @edgriffen and @Joe (whose JOE-NOR-4e4adc6b design links a nitrile to an Ugi structure).
This design links a ‘reversible’ covalent warhead (nitrile) to the amide nitrogen ADA-UCB-6c2cb422-1 in a manner that is unlikely to invert the cis/trans geometrical presence of amide (the problem is discussed here).
This analysis of the Cambridge Structural Database (CSD) suggests that using nitrogen (rather than sp3 carbon as in PET-UNK-bbe8d7ff-2 ) to link the nitrile to the amide nitrogen will not invert the cis/trans geometrical preference of the amide.
Here is the QELYOV structure (the torsion around the N-N bond is characteristic for this substructure).