Submission Details
Molecule(s):
CNC(=O)CN1C[C@]2(CCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)CN1C[C@]2(CCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2C[C@]3(CCCN(c4cncc5ccccc45)C3=O)c3cc(Cl)ccc3C2=O)CC1
CNC(=O)CN1C[C@]2(OCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2C[C@]3(OCCN(c4cncc5ccccc45)C3=O)c3cc(Cl)ccc3C2=O)CC1
CNC(=O)CN1C[C@]2(NCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2C[C@]3(NCCN(c4cncc5ccccc45)C3=O)c3cc(Cl)ccc3C2=O)CC1
CNC(=O)CN1C[C@@]2(C(=O)N(c3cncc4ccccc34)CCN2C)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2C[C@@]3(C(=O)N(c4cncc5ccccc45)CCN3C)c3cc(Cl)ccc3C2=O)CC1
PET-UNK-14142a25-10
Duplicate of:
EDJ-MED-8bb691af-8
CNC(=O)CN1CC2(CCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)CN1CC2(CCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2CC3(CCCN(c4cncc5ccccc45)C3=O)c3cc(Cl)ccc3C2=O)CC1
CNC(=O)CN1CC2(OCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2CC3(OCCN(c4cncc5ccccc45)C3=O)c3cc(Cl)ccc3C2=O)CC1
CNC(=O)CN1CC2(NCCN(c3cncc4ccccc34)C2=O)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2CC3(NCCN(c4cncc5ccccc45)C3=O)c3cc(Cl)ccc3C2=O)CC1
CNC(=O)CN1CC2(C(=O)N(c3cncc4ccccc34)CCN2C)c2cc(Cl)ccc2C1=O
CNC(=O)C1(N2CC3(C(=O)N(c4cncc5ccccc45)CCN3C)c3cc(Cl)ccc3C2=O)CC1
Design Rationale:
The designs in this submission consist of structural variations (replace pyrrolidinone with 6 membered ring) of the spirocyclic dihydroisoquinolone EDJ-MED-976a33d5-1. The pyrrolidine replacements include heteroatoms (may help with synthesis and controls logP; N likely to be neutral and could serve as synthetic handle). Each variation has been submitted with pendant glycyl amide and cyclopropane analog. The nine 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] Binding mode predicted for EDJ-MED-976a33d5-1 [4-12] Binding modes predicted for Binding modes predicted for Designs 1-9.