Submission Details
Molecule(s):
O=C(Nc1cncc2cc(F)ccc12)[C@@H]1CS(=O)(=O)Cc2ccc(Cl)cc21
CS(=O)(=O)c1ccc2cncc(NC(=O)[C@@H]3CS(=O)(=O)Cc4ccc(Cl)cc43)c2c1
COc1cc2c(NC(=O)[C@@H]3CS(=O)(=O)Cc4ccc(Cl)cc43)cncc2cn1
COc1cc2cncc(NC(=O)[C@@H]3CS(=O)(=O)Cc4ccc(Cl)cc43)c2cn1
O=C(Nc1cncc2cnccc12)[C@@H]1CS(=O)(=O)Cc2ccc(Cl)cc21
O=C(Nc1cncc2ccncc12)[C@@H]1CS(=O)(=O)Cc2ccc(Cl)cc21
Design Rationale:
Cyclic sulfones, derived from the structural prototype PET-UNK-1b92fa34-1, with P1 variations intended to address potential metabolism at P1. Rationale for the methoxynaphthyridines is discussed in PET-UNK-f4e47ebd submission notes.
Other Notes:
Design 2 has been previously submitted as the racemate ALP-POS-e6e0c683-4 and the methylsulfonyl substituent in this design appears to interact with the side chain amide NH of N142 (the protein structure in the PDB associated with this submission is from the complex with Design 2). Protein-ligand complexes (X11612 A chain) were energy minimized using Szybki (MMFF94S; amide carbonyl O and isoquinoline N fixed at the positions of the crystallographic ligand). The PDB file associated with this submission contains the following: [1] X11612 A chain from energy-minimized complex with Design 2 [2] X11612 A chain crystallographic ligand (MAT-POS-b3e365b9-1) [3] Binding mode predicted for PET-UNK-1b92fa34-1 [4-9] Binding modes predicted for designs 1-6.