[摘要]：Selective lowering of A beta(42) levels with small-molecule substrate targeting c-secretase modulators (sGSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. Here we present N-substituted carbazole-and O-substituted fenofibrate-derived sGSMs and their activity data. Seven out of 19 screened compounds exhibited promising activity against A beta(42) secretion at a low micromolar level. We presume that the sGSMs interact with lys624 at the membrane interface and that the lipophilic substituents anchor the compound orientation in the membrane. (C) 2009 Elsevier Ltd. All rights reserved.
