Sandgren Veronica, Belda Oscar, Kvarnström Ingemar, Lindberg Jimmy, Samuelsson Bertil, Dahlgren Anders
Department of Chemistry, Linköping University, S-581 83 Linköping, Sweden.
Medivir AB, Lunastigen 7, S-141 44 Huddinge, Sweden.
Open Med Chem J. 2015 Mar 31;9:13-26. doi: 10.2174/1874104501509010013. eCollection 2015.
A series of arylketo-containing P1-P3 linked macrocyclic BACE-1 inhibitors were designed, synthesized, and compared with compounds with a previously known and extensively studied corresponding P2 isophthalamide moiety with the aim to improve on permeability whilst retaining the enzyme- and cell-based activities. Several inhibitors displayed substantial increases in Caco-2 cell-based permeability compared to earlier synthesized inhibitors and notably also with retained activities, showing that this approach might yield BACE-1 inhibitors with improved properties.
设计、合成了一系列含芳基酮的P1 - P3连接的大环BACE - 1抑制剂，并将其与具有先前已知且经过广泛研究的相应P2间苯二甲酰胺部分的化合物进行比较，目的是在保留基于酶和细胞的活性的同时提高渗透性。与早期合成的抑制剂相比，几种抑制剂在基于Caco - 2细胞的渗透性方面有显著提高，并且值得注意的是其活性也得以保留，这表明这种方法可能会产生具有改进特性的BACE - 1抑制剂。
