Submission Details
Molecule(s):
O=C1Nc2cncc3ccc(cc23)OCCOC(=O)N2CCc3ccc(Cl)cc3C12
O=C1Nc2cncc3ccc(cc23)OCCOCC2NCc3ccc(Cl)cc3C12
Design Rationale:
Current challenge is to solve the met stab problem and moderate CYP inhibition. Macrocyclization with incorporation of heteroatoms on the tether will confer polarity on the compound and can potentially shift the metabolic soft spot. Secondly, rigidification through macrocyclization can improve potency.
Other Notes:
tether length may need to be optimized. N on bezopiperidine shifted keeping synthesis in mind.