Submission Details
Molecule(s):
NS(=O)(=O)c1cc(C(=O)O)c(Br)c(C(=O)N[C@H]2C[C@H]2F)c1
CCNC(=O)c1cc(S(N)(=O)=O)cc(C(=O)N[C@H]2C[C@H]2F)c1Br
NS(=O)(=O)c1cc(C(=O)N[C@H]2C[C@H]2F)c(Br)c(C(=O)N2CC2)c1
CNC(=O)c1cc(S(N)(=O)=O)cc(C(=O)N[C@H]2C[C@H]2F)c1Br
CC(C)CNC(=O)c1cc(S(N)(=O)=O)cc(C(=O)N[C@H]2C[C@H]2F)c1Br
NS(=O)(=O)c1cc(C(=O)NC2CC2)c(Br)c(C(=O)N[C@H]2C[C@H]2F)c1
COC(=O)CNC(=O)c1cc(S(N)(=O)=O)cc(C(=O)N[C@H]2C[C@H]2F)c1Br
CN(C)C(=O)c1cc(S(N)(=O)=O)cc(C(=O)N[C@H]2C[C@H]2F)c1Br
NS(=O)(=O)c1cc(C(=O)N[C@H]2C[C@H]2F)c(Br)c(C(=O)N[C@H]2CC[C@@H](C(=O)O)CC2)c1
CN(C)CCNC(=O)c1cc(S(N)(=O)=O)cc(C(=O)N[C@H]2C[C@H]2F)c1Br
NS(=O)(=O)c1cc(C(=O)NC2CCCCC2)c(Br)c(C(=O)N[C@H]2C[C@H]2F)c1
Design Rationale:
all 'Grown' from X_0946, aiming for ease of synthesis. Docked using GOLD. estimate for 'ligand efficiency' = GoldPLP score divided by mol_wt: scores: original X_0946 ligand = 0.11 best in this series = 0.16 best predicted docking pose DIFFERENT from X_0946. cyclopropyl group nicely fits in pocket where X_0946 binds. Sulfonamide makes H-bonds in another pocket. pdb of representative docked pose attached. (poses conserved across series).
Other Notes:
one of the NH hydrogens is quite close to the Br.