Submission Details
Molecule(s):
CN(C)c1ccc(N(Cc2ccsc2)C(=O)Cc2cncc3ccccc23)cc1
CS(=O)(=O)c1ccc(N(Cc2ccsc2)C(=O)Cn2nnc3ccccc32)cc1
PET-UNK-1901c25b-3
Duplicate of:
PET-UNK-7374c256-2
CN(C)c1ccc(N(Cc2ccn[nH]2)C(=O)Cn2nnc3ccccc32)cc1
Design Rationale:
Three structural variations of ALP-POS-d2866bdf-1 (x10876) that are intended to map the structure-activity relationship for this series. [1] Replace P1 benzotriazole with isoquinoline (good P1 substituent in 3-aminoquinoline series) [2] Replace dimethylamino group with methylsulfonyl (this is intended to exploit shallow concave region on protein surface, will also make the benzene ring less electron rich and is likely to lead to better solubility) [3] Replace thiophene with pyrazole in attempt to donate a hydrogen bond to backbone carbonyl oxygen of E166 (this has been observed in fragment structures such as AAR-POS-d2a4d1df-2 (X0104).
Other Notes:
The docking file contains the protein and ligand structures for ALP-POS-d2866bdf-1 (X10876) and proposed binding modes for the three designs.