Submission Details
Molecule(s):
O=C1c2ccc(Cl)cc2[C@@]2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1nncs1
O=C1c2ccc(Cl)cc2[C@@]2(CC(=O)N(c3cncc4ccccc34)C2=O)CN1Cc1nncs1
O=C1c2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1nncs1
O=C1c2ccc(Cl)cc2C2(CC(=O)N(c3cncc4ccccc34)C2=O)CN1Cc1nncs1
Design Rationale:
The two designs in this submission replace pendant amides of the P2-dihydroquinolones EDJ-MED-8bb691af-8 and MAT-POS-1bed62cf-2 with 1,3,4-thiadiazole. My view (see submissions PET-UNK-77d5678a and PET-UNK-aa57768f) is that 1,3,4-thiadiazole is likely to be better for P2-tetrahydroisoquinoline while 1,2,4-oxadiazole is likely to be better for P2-dihydroisquinoline. I would recommend that PET-UNK-aa57768f-1 | PET-UNK-77d5678a-2 | PET-UNK-7e9559de-1 | PET-UNK-77d5678a-1 be considered as higher priority than either of the designs in this submission. The racemates for the designs have been included in this submission.
Other Notes:
Protein-ligand complexes (P1788 A chain) were energy-minimized using Szybki (MMFF94S). The PDB file associated with this submission contains the following: [1] P1788 A chain protein structure [2] P1788 A chain crystallographic ligand (MAT-POS-dc2604c4-1) [3-4] Binding modes predicted for Designs 1-2.