A fragment-based docking procedure followed by substructure search were used to identify active-site β-secretase inhibitors from a composite set of about 300 000 and a library of nearly 180 000 small molecules, respectively. EC50 values less than 10 μM were measured in at least one of two different mammalian cell-based assays for 12 of the 72 purchased compounds. In particular, the phenylureathiadiazole 2 and the diphenylurea derivative 3 are promising lead compounds for β-secretase inhibition.
BT - Journal of Medicinal Chemistry C1 - 0067 DA - 2005 Aug 11 DO - 10.1021/jm050499d IS - 16 J2 - J. Med. Chem. LA - eng M3 - Research Article N2 -A fragment-based docking procedure followed by substructure search were used to identify active-site β-secretase inhibitors from a composite set of about 300 000 and a library of nearly 180 000 small molecules, respectively. EC50 values less than 10 μM were measured in at least one of two different mammalian cell-based assays for 12 of the 72 purchased compounds. In particular, the phenylureathiadiazole 2 and the diphenylurea derivative 3 are promising lead compounds for β-secretase inhibition.
PY - 2005 SP - 5108 EP - 5111 T2 - Journal of Medicinal Chemistry TI - Discovery of cell-permeable non-peptide inhibitors of beta-secretase by high-throughput docking and continuum electrostatics calculations VL - 48 SN - 0022-2623 ER -