Submission Details
Molecule(s):
O=C(Nc1cncc2ccccc12)C12CCC(O1)c1ccccc12
O=C(Nc1cncc2ccccc12)C12CCC(O1)c1ccc(Cl)cc12
Design Rationale:
Tie methoxy of EDJ-MED-d08626de-1back to form a [2.2.1]bicyclo system. Increased rigidity and decrease in logP will reduce clearance. Des-chloro template appears widely available commercially and therefore a benchmark of potency can be rapidly assessed. The [2.2.1]bicyclo system is readily prepared via Diels Alder cycloaddition of benzyne (generated via anthranilic acid) to methyl furoate. This route should be amenable to preparing analogs halogenated on the aryl ring. Methods of resolving enantiomers are described in the literature, and it is possible the enantiomers are commercially available.