Design and synthesis of 3＇-（prop-2-yn-1-yloxy）-biphenyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

Abstract Based on the lead compounds 1 and 2 , a series of novel BACE1 inhibitors were designed and synthesized, among which compound 9h exhibited a 60 fold improvement in potency over the lead compound 1 . This represents a good lead for the discovery of more promising BACE1 inhibitors for the potential treatment of AD. The result also showed that the prop-2-yn-1-yloxy is a suitable fragment for modification of cyclic acylguanidine BACE1 inhibitors.