Submission ALP-POS-e2fddb0f

Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/ALP-POS-e2fddb0f

Hi @alphalee I would expect both of these designs to to adopt conformations in which the carbonyl group is coplanar with the aromatic ring (in the bound conformation of
ADA-UCB-6c2cb422-1
, the isoquinoline ring and carbonyl group are mutually non-coplanar. The carbonyl groups on the designs are likely to be relatively electrophilic and I’d expect any inhibition observed for compounds like these to be due to acylation of the catalytic cysteine (I’d also expect
ALP-POS-c59291d4-5
to function in this manner). Acylimidazoles (and related compounds) have been reported to be cruzain inhibitors and I would expect the activity of these inhibitors to be due to acylation of the catalytic cysteine.

Thanks @pwkenny! Great points. These are side products en route to synthesising JAG-UCB-52b62a6f-9 and JAG-UCB-52b62a6f-12, so we are just testing them opportunistically.

No worries, Alpha, and I hope that it’s useful to have designs discussed.