Submission Details
Molecule(s):
CS(=O)(=O)CCO[C@@]1(C(=O)Nc2cncc3ccccc23)CN(S(C)(=O)=O)Cc2ccc(Cl)cc21
CN(C)S(=O)(=O)N1Cc2ccc(Cl)cc2[C@](OCCS(C)(=O)=O)(C(=O)Nc2cncc3ccccc23)C1
CS(=O)(=O)CCO[C@@]1(C(=O)Nc2cncc3ccccc23)CNC(=O)c2ccc(Cl)cc21
CN1C[C@@](OCCS(C)(=O)=O)(C(=O)Nc2cncc3ccccc23)c2cc(Cl)ccc2C1=O
CS(=O)(=O)CCO[C@@]1(C(=O)Nc2cncc3ccccc23)CCS(=O)(=O)c2ccc(Cl)cc21
CS(=O)(=O)CCO[C@@]1(C(=O)Nc2cncc3ccccc23)CS(=O)(=O)Cc2ccc(Cl)cc21
COCCO[C@@]1(C(=O)Nc2cncc3ccccc23)CS(=O)(=O)Cc2ccc(Cl)cc21
Design Rationale:
The designs in this submission elaborate the methoxy substituent (configurational lock which also appears to be beneficial for antiviral activity) to MeSO2CH2CH2O- (Designs 1-6; see PET-UNK-4880b143-1 which has been ordered for synthesis) or MeOCH2CH2O- (Design 7; see PET-UNK-ad758083 submission notes) for some scaffolds of potential interest to the design team
Other Notes:
Protein-ligand complexes (P0157 A chain from complex with Design 1) were energy-minimized using Szybki (MMFF94S). As modelled, one of the sulfonyl oxygens in each of Designs 1-6 interacts with both the side chain amide NH of N142 and (intramolecularly) with the amide NH of the ligand. As modelled, the methoxy oxygen of Design 7 accepts a hydrogen bond from the side chain amide N142 although this is not entirely convincing and the methoxy oxygen could also be solvent exposed. The PDB file associated with this submission contains the following: [1] P0157 A chain from complex with design 1 [2] P0157 A chain crystallographic ligand (PET-UNK-29afea89-2) [3-8] Binding mode predicted for Designs 1-6 [9] Binding mode predicted for Design 7.