Submission Details
Molecule(s):
NC(=O)C1CN(C(=O)CCl)CCN1Cc1cccc(Cl)c1
CC1(C)CN(C(=O)CCl)CCN1Cc1cccc(Cl)c1
CC(C)C[C@@H]1CN(C(=O)CCl)CCN1Cc1cccc(Cl)c1
CC(C)[C@@H]1CN(Cc2cccc(Cl)c2)CCN1C(=O)CCl
O=C(CCl)N1CCN(Cc2cccc(Cl)c2)CC1c1ccccc1
O=C(CCl)N1CCN(Cc2cccc(Cl)c2)C(c2ccc(Cl)cc2)C1
CC(C)(C)NC(=O)[C@@H]1CN(C(=O)CCl)CCN1Cc1cccc(Cl)c1
O=C(CCl)N1CC2CC1CN2Cc1cccc(Cl)c1
O=C(CCl)N1CCN(Cc2cccc(Cl)c2)C(c2cccs2)C1
O=C(CCl)N1CCN(Cc2cccc(Cl)c2)C[C@@H]1Cc1ccccc1
Design Rationale:
The inspiration is X_0770, one of the covalent fragments. I based these designs on a simple 3-step synthetic route with commercially available boc-protected piperazines. First step is nucleophilic substitution with 1-(bromomethyl)-3-chlorobenzene, then deprotection, and then amidation with 2-chloroacetyl chloride. I docked them using the constrained scaffold of X_0770, and chose that seem compatible. Also, I predict that the ones with the substitution next to the chloroacetamide will have reduced electrophile reactivity due to steric hindrance. If you have any questions, feel free to email me.