표제지
목차
I. 서론 8
II. 결과 및 고찰 14
2.1. Benzothiazole과 NSAIDs 구조기반 Dimer 디자인 14
2.2. Synthesis of benzothiazole based dimer 20
2.2.1. Synthesis of benzothiazole aniline 20
2.2.2. Synthesis of 2-(4-Amino-phenyl)-benzothiazol-6-ol Heptane dimer 21
2.2.3. Synthesis of 2-(4-Amino-phenyl)-benzothiazol-6-ol 1-Propoxy-propane dimer 22
2.2.4. Synthesis of 2-(4-Amino-phenyl)-benzothiazol-6-ol 1,4-Diethyl-benzene para dimer 23
2.2.5. Synthesis of 2-(4-Amino-phenyl)-benzothiazol-6-ol 1,4-Diethyl-benzene meta dimer 24
2.3. Synthesis of NSAIDs-analog based dimer 25
2.3.1. Synthesis of 2-(4-{3-[4-(1-Carboxy-ethyl)-phenoxy]-propoxy}-phenyl)-propionic acid 25
2.3.2. Synthesis of 2-(4-{3-[4-(1-Carboxy-ethyl)-phenoxy]-2-hydroxy-propoxy}-phenyl)-propionic acid 26
2.3.3. Synthesis of 2-(6-{3-[6-(1-Carboxy-ethyl)-naphthalen-2-yloxy]-propoxy}-naphthalen-2-yl)-propionic acid 27
2.3.4. Synthesis of 2-(6-{3-[6-(1-Carboxy-ethyl)-naphthalen-2-yloxy]-2-hydroxy-propoxy}-naphthalen-2-yl)-propionic acid 28
2.4. Disaggregation assay 29
III. 결론 31
IV. 재료 및 실험 방법 34
V. 참고문헌 48
ABSTRACT 53
APPENDIX 55
Table 1. Molecular weights and CLog P values of dimers based on benzothiazole and NSAIDs structure 18
Table 2. Dimers of benzothiazole, NSAIDs analog 31
Figure 1. Current medications for Alzheimer's disease. 9
Figure 2. The generation of Aβ plaques based on amyloid hypothesis. 10
Figure 3. Chemical structures of representative amyloid imaging agents 12
Figure 4. Non-steroidal anti-inflammatory drugs (NSAIDs). 13
Figure 5. The chemical structure of [N-2-[fluoropropyl]-2-(4'-(methylamino) phenyl)-6-hydroxybenzothiazole (FMHT) 15
Figure 6. Cromolyn Sodium 15
Figure 7. Fisetin 15
Figure 8. General dimer structures based on benzothiazole and NSAIDs structure. 17
Figure 9. Thioflavin T disaggregation assay using compound 19a (Compound A), 28a (Compound B). 30
Scheme 1. Synthesis of benzothiazole aniline (6) 4-(6-Methoxymethoxy-benzothiazol-2-yl)-phenylamine 20
Scheme 2. Synthesis of benzothiazole based dimer (9) 21
Scheme 3. Synthesis of benzothiazole based dimer (12) 22
Scheme 4. Synthesis of benzothiazole based dimer (14) 23
Scheme 5. Synthesis of benzothiazole based dimer (16) 24
Scheme 6. Synthesis of NSAIDs based dimer (20) 25
Scheme 7. Synthesis of NSAIDs based dimer (22) 26
Scheme 8. Synthesis of NSAIDs based dimer (27 27
Scheme 9. Synthesis of NSAIDs based dimer (29) 28