Submission Details

FRA-DIA-0fa076fe
Molecule(s):
O=C(Nc1cncc2ccccc12)[C@H]1COc2c(Cl)cccc21

FRA-DIA-0fa076fe-1

O=C(Nc1cncc2ccccc12)[C@H]1COc2c(Cl)cccc21

3-aminopyridine-like Check Availability on Manifold View
O=C(Nc1cncc2ccccc12)[C@H]1COc2c(Cl)cc(O)cc21

FRA-DIA-0fa076fe-2

O=C(Nc1cncc2ccccc12)[C@H]1COc2c(Cl)cc(O)cc21

3-aminopyridine-like Check Availability on Manifold View
O=C(Nc1cc(=O)[nH]c2ccccc12)[C@H]1COc2c(Cl)cc(O)cc21

FRA-DIA-0fa076fe-3

O=C(Nc1cc(=O)[nH]c2ccccc12)[C@H]1COc2c(Cl)cc(O)cc21

3-aminopyridine-like Check Availability on Manifold View
O=C(Nc1cc(=O)[nH]c2ccccc12)[C@H]1COc2c(Cl)cccc21

FRA-DIA-0fa076fe-4

O=C(Nc1cc(=O)[nH]c2ccccc12)[C@H]1COc2c(Cl)cccc21

3-aminopyridine-like Check Availability on Manifold View
Design Rationale:

Improving on FRA-DIA-b66f7109, specifically: (a) removing the betalactam, leaving (1) or keeping (2) the ether oxygen, which H-bonds with backbone O of R188; (b) same as (a) but replacing the isoquinoline in P1 with a quinolone, but importantly (!!) with the amide reversed relative to the quinolones already made, so that the amide oxygen can point down into the backbone N/O hole of G166, axially to the 5-membered ring, as in VLA-UCB-1dbca3b4-15. (A few such reverse-amide-quinolones were designed, including MAR-UCB-f313ec4d-1, but none made.) Views here: https://fragalysis.diamond.ac.uk/viewer/react/projects/234/199

Other Notes:

Alpha Lee said (Slack) that (1) is a one-step synthesis - but the oxygen is almost certainly important to keep, so (2) is probably the one worth making. Ditto (3) vs (4).

Inspired By:
Discussion:

Contributor: Frank von Delft, Diamond Light Source - Thu, 24 Sep 2020 05:37:09 +0000