Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/ALP-POS-477dc5b7
Hi Alpha @alphalee
Before synthesizing ALP-POS-477dc5b7-4 or ALP-POS-477dc5b7-5 I would recommend considering PET-UNK-c9c1e0d8-4 (currently ordered) and PET-UNK-c9c1e0d8-3 to chek that the annulation does not compromise potency. The synthesis of the spiro compounds is likely to be more complex and the greater rigidity of the molecular structures reduces the margin of error when positioning the P2 substituent. Here is some discussion, which also includes a link to dockings, that @mc-robinson and I were having that may be of interest.
My main interest in the lactams is that I currently consider the 6-membered ring to represent the best opportunity for linking a reversible warhead to a 3-aminopyridine. Here are notes in which I make the case for reversible warheads and try to explain why we are likely to need a ring to position the warhead.