Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors

Utilizing a structure based design approach, combined with extensive medicinal chemistry execution, highly selective, potent and novel BACE1 inhibitor 8 (BACE1 Alpha assay IC50 = 8 nM) was made from a weak μM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed.