Submission Details
Molecule(s):
O=C(CCN1CCOCC1)Nc1cccnc1CNC(=O)NC1CC1
CN1CCC(OCC(=O)Nc2ccncc2CNC(=O)NC2CC2)CC1
CN1CCN(CCC(=O)Nc2cccnc2CNC(=O)NC2CC2)CC1
CN1CCN(CCC(=O)Nc2ccncc2CNC(=O)NC2CC2)CC1
CN1CCC(OCC(=O)Nc2cccnc2CNC(=O)NC2CC2)CC1
CN1CCN(CCC(=O)Nc2cccnc2CNC(=O)NC2CCCC2)CC1
CN1CCN(CCC(=O)Nc2cccnc2CNC(=O)NCC2CC2)CC1
Design Rationale:
By eye, docking Combination of 107, 354 and 397
Other Notes:
Aromatic of 354 doesn't interact strongly with protein so can be safely removed. Cyclopropyl of 397 sits close to the top of a lipophilic cavity but without filling it so expect enlarging this moiety will give a potency enhancement. Proposed synthesis: acylate EN300-131175 with acryloyl chloride, then add N-methylpiperazine in a Michael reaction. Reduce the nitrile with hydrogenation before forming the urea. A 4 step synthesis combines 3 fragments. The other suggested compounds can be made from variations on this. Obviously many analogues other than those suggested here are also possible.