Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors

Shangguan, Shihao; Wang, Fei; Liao, Yong; Yu, Haiping; Li, Jia; Huang, Wenhai; Yu, Lu-shan; Hu, Yongzhou; Sheng, Rong

doi:10.3390/molecules18033577

Cited by 4 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[298][299][300][301][302][303][304][305][306] The corresponding sulfur containing heterocycles, such as aminothiadiazines, have also been investigated. 307 Compound 140 (Fig. 63) showed an IC 50 of 9.9 mM.…”

Section: (E) Aminothiazoline-and Aminooxazoline-based Inhibitorsmentioning

confidence: 98%

See 1 more Smart Citation

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease

2014

View full text Add to dashboard Cite

BACE1 (β-secretase, memapsin 2, Asp2) has emerged as a promising target for the treatment of Alzheimer's Disease. BACE1 is an aspartic protease which functions in the first step of the pathway leading to the production and deposition of amyloid-β peptide (Aβ). Its gene deletion showed only mild phenotypes. BACE1 inhibition has direct implications in the Alzheimer's Disease pathology without largely affecting viability. However, inhibiting BACE1 selectively in vivo has presented many challenges to medicinal chemists. Since its identification in 2000, inhibitors covering many different structural classes have been designed and developed. These inhibitors can be largely classified as either peptidomimetic or non-peptidic inhibitors. Progress in these fields resulted in inhibitors that contain many targeted drug-like characteristics. In this review, we describe structure-based design strategies and evolution of a wide range of BACE1 inhibitors including compounds that have been shown to reduce brain Aβ, rescue the cognitive decline in transgenic AD mice and inhibitor drug candidates that are currently in clinical trials.

show abstract

Section: (E) Aminothiazoline-and Aminooxazoline-based Inhibitorsmentioning

confidence: 98%

“…307 Compound 140 (Figure 63) showed an IC 50 of 9.9 μM. A modeling study showed that the naphthylbenzylamide extends into the S3 site while the amino group hydrogen bonds to Asp32 and Gly34.…”

Section: Nonpeptide Inhibitorsmentioning

confidence: 99%