Submission Details
Molecule(s):
O=C1c2ccc(Cl)cc2[C@@]2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1ccno1
O=C1c2ccc(Cl)cc2[C@@]2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1ccon1
O=C1c2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1ccno1
O=C1c2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1ccon1
Design Rationale:
Each of the two designs in this submission replaces the pendant amide of EDJ-MED-8bb691af-8 with isoxazole. Isoxazole is more amide-like than the 1,3,4-oxadiazole of PET-UNK-aa57768f-1 in that the amide NH is replaced by an aromatic CH rather than a non-polar oxygen although I’d anticipate that the oxadiazole will be more resistant to metabolism. The two designs have also been submitted as racemates.
Other Notes:
Protein-ligand complexes (P1090 A chain) were energy-minimized using Szybki (MMFF94S). The PDB file associated with this submission contains the following: [1] P1090 protein structure [2] P1090 A chain crystallographic ligand (MAT-POS-4223bc15-23) [3-4] Binding modes predicted for Designs 1-2
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