946130-80-9Relevant articles and documents
4-Substituted 2-amino-3,4-dihydroquinazolines with a 3-hairpin turn side chain as novel inhibitors of BACE-1
Chen, Grace Shiahuy,Chern, Ji-Wang,Hsieh, Chen-En,Hung, Pei-Yun,Jagtap, Ajit Dhananjay,Kondekar, Nagendra B.,Yang, Chia-Ron
, (2020/01/11)
Herein, we report the identification, design, and synthesis of a series of 4-substituted 2-amino-3,4-dihydroquinazolines with hairpin turn side chains as novel inhibitors of BACE-1. The dihydroquinazoline derivatives were rationally designed by modifying the amide group and relocating the α -hydrophobic substituent on the hairpin turn side chain of lead compound 2 to the C4-position on the 3,4-dihydroquinazoline scaffold to facilitate interactions with the S1, S2 and S1′ subsites of BACE-1. Among these derivatives, two compounds exhibited potent BACE-1 inhibitory activity: 4-methyl-substituted (22a, BACE-1 CFA IC50 = 0.38 μM; BACE-1 WCA IC50 = 0.14 μM) and 4-cyclohexylmethyl-substituted (22b, BACE-1 CFA IC50 = 0.49 μM; BACE-1 WCA IC50 = 0.14 μM) 2-amino-3,4-dihydroquinazoline, each bearing a side chain of N-cyclohexyl-N-((1-methyl-1H-pyrazol-4-yl)methyl amide. The results suggest that the structural modifications maintain the hairpin turn topology similar to that of compound 2 and provide an additional interaction with the S2 subsite.
2-AMINO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)
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Page/Page column 39, (2008/12/07)
The present invention is directed to 2-amino-quinoline derivatives, pharmaceutical compositions containing them and their use in the treatment of Alzheimer's disease (AD) and related disorders. The compounds of the invention are inhibitors of β-secretase, also known as β-site cleaving enzyme and BACE, BACE1, Asp2 and memapsin2.
2-AMINO-3,4-DIHYDRO-QUINOLINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)
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Page/Page column 30, (2010/11/28)
The present invention is directed to 2-amino-3,4-dihydro-quinoline derivatives, pharmaceutical compositions containing them and their use in the treatment of Alzheimer's disease (AD) and related disorders. The compounds of the invention are inhibitors of β-secretase, also known as β-site cleaving enzyme and BACE, BACE1, Asp2 and memapsin2.