Submission Details
Molecule(s):
CC(C)(C)c1ccc(N(C(=O)c2cc[nH]c2)C(C(=O)NCCc2cccc(F)c2)c2cccnc2)cc1
CC(C)(C)c1ccc(N(C(=O)c2nc[nH]n2)C(C(=O)NCCc2cccc(F)c2)c2cccnc2)cc1
CC(C)(C)c1ccc(N(C(=O)c2ccccn2)C(C(=O)NCCc2cccc(F)c2)c2cccnc2)cc1
CC(C)(C)c1ccc(N(C(=O)c2ccco2)C(C(=O)NCCc2cccc(F)c2)c2cccnc2)nc1
CC1(c2ccc(N(C(=O)c3ccco3)C(C(=O)NCCc3cccc(F)c3)c3cccnc3)cc2)CC1
CC(C)(C#N)c1ccc(N(C(=O)c2ccco2)C(C(=O)NCCc2cccc(F)c2)c2cccnc2)cc1
Design Rationale:
Six Ugi-based designs. First three target the backbone carbonyl oxygen of T26 with hydrogen bond donors. Second three aim to reduce lipophilicity of P2 substituent.
Other Notes:
The pdb file associated with the submission contains the following structures: (1) Edited version of 6w63 pdb protein stucture (2) Ligand from 6w63 pdb structure (3) Ligand from x2572 (one of the t-Bu methyls is replaced by nitrile in the 6th design) (4-9) Designs 1-6. The fluorophenethyl substituent of each design has been truncated to methyl for the structure models. I will provide additional information as a comment on the submission.