کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1362454 | 981488 | 2006 | 17 صفحه PDF | دانلود رایگان |

With the aim of developing small molecular non-peptide β-secretase (BACE) inhibitors, Leu∗Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure–activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu∗Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (<600).
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Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 13, 1 July 2006, Pages 4535–4551