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Synthesis of (3S,4S)-4-aminopyrrolidine-3-ol derivatives and biological evaluation for their BACE1 inhibitory
Quang De Tran1, Sukumar Bepary2, Ge Hyeong Lee2
1Department of Medicinal and Pharmaceutical Chemistry, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-333, Republic of Korea.
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.
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