Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/MIC-UNK-50cce87d
I think that some of these compounds (5-12) could exist as a mixture of atropoisomers because of great steric hindrance near amide, and I’ll tag @pwkenny in case he’s interested
Thanks for the tag and I think that atropoisomerism would be problem that we can do without. While I agree that it would be a good idea to investigate the effect on potency of substituting at C5 of the isoquinoline, my preferred approach would be to first determine the effect of methylation before synthesizing other analogs.
The parent 6 and 5-membered lactams were in the PET-UNK-c9c1e0d8 as compounds 3 and 4 respectively. I expressed a preference for the 6-membered lactam PET-UNK-c9c1e0d8-3 over the 5-membered lactam PET-UNK-c9c1e0d8-4 since it appears to fit more easily into the binding site and is likely to present a better vector for covalent targeting the catalytic cysteine (e.g. PET-UNK-3e354a91-1). However, it was the 5-membered lactam that was actually prioritized for synthesis.