Submission Details
Molecule(s):
CC(=O)N1CCNC2NC(=O)N(c3cccnc3)C21
CC(=O)N1CCN(Cc2ccccc2)C2NC(=O)N(c3cccnc3)C21
CC(=O)c1ccc(Br)c2[nH]c(=O)n(-c3cccnc3)c12
CC(=O)c1ccc(Cc2ccc(Br)cc2)c2[nH]c(=O)n(-c3cccnc3)c12
CC(=O)c1ccc(C#N)c2[nH]c(=O)n(-c3cccnc3)c12
Design Rationale:
I looked at the urea and piperazine series of fragments and combined them to create bicyclic scaffolds. The scaffolds with the saturated N-cyclic rings would be hard to make, but maintain the piperazine core. I've kept the N free for analogue synthesis to alkylate. The aromatic scaffolds would be much easier to synthesise and much more amenable to analogue synthesis and SAR studies. I've attached a bromide where cross-coupling could be used to attach aromatic groups to maintain the 'aromatic wheel' and probe that pocket further.
Other Notes:
I think the scaffolds where I've changed the piperazine ring could be more promising. The nitrogens on the ring don't seem to be involved in H-bonding so I don't think a lot will be lost by removing them. Also, I think making the bicyclic system planar is better for maintaining the conformation needed for the urea.