| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
|---|
| Outline of Final Research Achievements |
Two strategies were examined to transform from substrate-based protease inhibitor to non-peptide drug-like low molecular compound; the one is cyclization combined with introduction of suitable functional groups on the ring structure and the another is utilization of fused-ring structure as a novel scaffold of inhibitors. Inhibitors for BACE1, engaged in production of an amyloid beta in Alzheimer disease, and inhibitors for SARS 3CL protease, essential for proliferation of SARS corona virus, were selected for the objects.
In the design of BACE1 inhibitors, cyclization via an olefin bond combined with beta site methyl groups was found to be most effective. In the design of inhibitors for SARS 3CL protease, two new hydrophobic scaffolds, decahydroisoquinoline and octahydroisochromene, were found to be effective fused-ring structures to incorporate several functional groups interacting with the protease.
|
