Submission Details
Molecule(s):
O=C(CCl)N1CCN(C(c2ccccc2)C(CCO)CCO)CC1
O=C(CCl)N1CCN(C(c2ccccc2)C2CCOCC2)CC1
O=C(CCl)N1CCN(C(c2ccccc2)C2CCS(=O)(=O)CC2)CC1
O=C(CCl)N1CCN(C(c2ccccc2)C2CCNCC2)CC1
CN1CCC(C(c2ccccc2)N2CCN(C(=O)CCl)CC2)CC1
O=C(CCl)N1CCN(C(c2ccccc2)C2CCCCC2)CC1
O=C(CCl)N1CCN(C(c2ccccc2)C(CO)CO)CC1
O=C(CO)N1CCC(C(c2ccccc2)N2CCN(C(=O)CCl)CC2)CC1
O=C1CC(C(c2ccccc2)N2CCN(C(=O)CCl)CC2)CCN1
Design Rationale:
A series of derivatives, having the chloroacetamide motif and the apolar tail, with an additional side chain that can be directed to other subpocket and undergo to apolar (cyclohexyl) or polar interactions (the other) with the AA residue of the enzyme. The polar side chain could be also be solvent exposed and better contribute to direct the other two main fragment to the active site. The main feature is that this series of compounds can be rapidly synthesized by key petasis reaction, between benezene boronic acid (or other arylboronic derivatives), N-monoprotected piperazine and carbonyl compound (for the siede chain). Easy exploration of the molecular space is so readily possible. All building blocks are commercially available.