Submission Details
Molecule(s):
O=C1c2ccc(Cl)cc2[C@@]2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1nnco1
N#CCN1C[C@]2(CCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
C#CCN1C[C@]2(CCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
O=C1c2ccc(Cl)cc2[C@@]2(CCCN(c3cncc4ccccc34)C2=O)CN1Cc1nnco1
N#CCN1C[C@]2(CCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
C#CCN1C[C@]2(CCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
O=C1c2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)CN1Cc1nnco1
N#CCN1CC2(CCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
C#CCN1CC2(CCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
O=C1c2ccc(Cl)cc2C2(CCCN(c3cncc4ccccc34)C2=O)CN1Cc1nnco1
N#CCN1CC2(CCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
C#CCN1CC2(CCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
Design Rationale:
The six designs in this submission combine two spirocyclic fusions (succinimide; glutarimide) of dihydroisoquinolone scaffold with three replacements (oxadiazolymethyl, cyanomethyl, propargyl) for the potentially labile pendant amide. Although the pendant amide NH appears necessary for the tetrahydrogisoquinoline scaffold, it is much less clear that this is the case for the dihydroisoquinolone scaffold. The six 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) [3-8] Binding modes predicted for Designs 1-6.
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