Submission Details
Molecule(s):
O=C(Nc1cccnc1)N(CN1CCOCC1)c1cccc(Cl)c1
N=C(N)CCN(C(=O)Nc1cccnc1)c1cccc(Cl)c1
O=C(Nc1cccnc1)N(CN1CCC(O)CC1)c1cccc(Cl)c1
O=C(Nc1cccnc1)N(CN1CCNCC1)c1cccc(Cl)c1
CN1CCN(CN(C(=O)Nc2cccnc2)c2cccc(Cl)c2)CC1
O=C(Nc1cccnc1)N(CCN1CCOCC1)c1cccc(Cl)c1
JOR-UNI-2fc98d0b-7
Duplicate of:
DAR-DIA-23aa0b97-14
O=C(Nc1cccnc1)Nc1cccc(Cl)c1
O=C(Nc1cccnc1)N(CCC1CC1)c1cccc(Cl)c1
O=C(Nc1cccnc1)N(CCN1CCCOCC1)c1cccc(Cl)c1
O=C(Nc1cccnc1)N(CCN1CCNCC1)c1cccc(Cl)c1
CN1CCN(CCN(C(=O)Nc2cccnc2)c2cccc(Cl)c2)CC1
O=C(Nc1cccnc1)N(CCC1CCCCC1)c1cccc(Cl)c1
O=C(Nc1cccnc1)N(CCN1CCC(O)CC1)c1cccc(Cl)c1
CC1CCN(CN(C(=O)Nc2cccnc2)c2cccc(Cl)c2)CC1
CC1CCN(CCN(C(=O)Nc2cccnc2)c2cccc(Cl)c2)CC1
O=C(Nc1cccnc1)N(CN1CCCCC1)c1cccc(Cl)c1
O=C(Nc1cccnc1)N(CCN1CCCCC1)c1cccc(Cl)c1
Design Rationale:
These compounds are based on the fragment X_0434. We propose functionalization of the benzene ring with a halogen atom to occupy the pocket formed by the side chains of M165 H41 and F181 (as several other fragments occupy this pocket) and we aim at occupying an adjacent pocket via a double alkylation of the urea with a series of groups inspired either by the structures of other fragments (e.g: X_0991) or other groups common in MedChem (e.g. morpholine). The compounds were manually built in Maestro and minimised to reduce steric clashes.
Other Notes:
We followed a strategy similar to the one described in De Simone et al Chemical Science 2018 (https://doi.org/10.1039/C8SC03831G) and we suggest that the chemistry described in that work may be helpful to devise synthetic routes for these compounds.