Conformational restriction approach to β-secretase (BACE1) inhibitors: effect of a cyclopropane ring to induce an alternative binding mode.


Improvement of a drug's binding activity using the conformational restriction approach with sp³ hybridized carbon is becoming a key strategy in drug discovery. We applied this approach to BACE1 inhibitors and designed four stereoisomeric cyclopropane compounds in which the ethylene linker of a known amidine-type inhibitor 2 was replaced with chiral… (More)
DOI: 10.1021/jm3011405