Submission Details
Molecule(s):
O=C(Nc1cncc2ccccc12)[C@@H]1CS(=O)(=O)c2ccc(Cl)cc21
CO[C@@]1(C(=O)Nc2cncc3ccccc23)CS(=O)(=O)c2ccc(Cl)cc21
Design Rationale:
It’s possible that geometric differences (bond lengths and angles) between sulfur and first row elements could result in the five-membered ring compound being more potent than analog with a six-membered ring (the opposite trend is observed for the cyclic ethers MAT-POS-b3e365b9-1 and EDJ-MED-12c115cc-1). While this is difficult to predict, the two designs in this submission may be worth looking at if cyclic sulfones are of interest to the design team.
Other Notes:
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 X11612 A chain was used for modelling. The PDB file associated with this submission contains the following: [1] X11612 A chain from complex with Design 1 [2] X11612 A chain crystallographic ligand (MAT-POS-b3e365b9-1) [3-4] Binding modes predicted for MIC-UNK-91acba05-3 (R enantiomer) | PET-UNK-1b92fa34-1 [5-6] Binding modes predicted designs 1-2.