title: Synthesis of (3S,4S)-4-aminopyrrolidine-3-ol derivatives and biological evaluation for their BACE1 inhibitory activities.
abstract: Synthesis, SAR study and BACE1 inhibitory activity of (3S,4S)-4-aminopyrrolidine-3-ol derivatives (2) were described. The compound 7c exhibited more inhibition activity than 11a (IC50: 0.05μM vs 0.12μM, respectively), but the latter was more effective in cell-based assay (IC50: 1.7μM vs 40% inhibition by 7c @ 10μM) due to the relatively higher cell permeability. Most of the compounds showed high selectivity over BACE2 and cathepsin D. This work will provide useful information for further structural modifications to develop potent BACE1 inhibitors in cell.
authors.affiliation: Department of Medicinal and Pharmaceutical Chemistry, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Republic of Korea.
authors.forename: Quang
authors.initials: Q
authors.lastname: De Tran
authors.affiliation: Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Bepary
authors.affiliation: Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Ge Hyeong
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Department of Medicinal and Pharmaceutical Chemistry, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Republic of Korea; Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Heeyeong
authors.initials: H
authors.lastname: Cho
authors.affiliation: Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Woo Kyu
authors.initials: WK
authors.lastname: Park
authors.affiliation: Department of Medicinal and Pharmaceutical Chemistry, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Republic of Korea; Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea. Electronic address: heejong@krict.re.kr.
authors.forename: Hee-Jong
authors.initials: HJ
authors.lastname: Lim
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D016716:PC12 Cells; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: C000609349:4-aminopyrrolidine-3-ol; D011480:Protease Inhibitors; D011759:Pyrrolidines; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
keywords: Alzheimer’s disease; BACE1 inhibitors; Pyrrolidine derivatives