Submission Details
Molecule(s):
O=C(NCCN1CCN(C(=O)CCl)CC1)c1ccccc1
O=C(NCCN1CCN(C(=O)CCl)CC1)c1cccc2ccccc12
O=C(NCCN1CCN(C(=O)CCl)CC1)c1cccnc1
O=C(CCl)N1CCCC(n2cc(-c3ccccc3)nn2)C1
O=C(CCl)N1CCCC(n2cc(-c3ccc(Cl)cc3)nn2)C1
O=C(CCl)N1CCCC(n2cc(COCc3ccccc3)nn2)C1
O=C(CCl)N1CCN(Cc2cn(Cc3ccccc3)nn2)CC1
Design Rationale:
We covalently docked all covalent fragments that were crystallized and focused on those that gave a reasonable overlap of the docked structure with the crystallized one. Most of these were piperazines with a CH2-aryl substituent. We suspect this CH2 gives the necessary flexibility to reach the S2 pocket. In the current design, we focused on ease of synthesis while adding more substituents to reach the S2 specificity pocket. Structures are currently being covalently docked to evaluate this.