Title Page
Contents
LIST OF ABBREVIATIONS 11
ABSTRACT 16
I. Introduction 18
1. Carbonic anhydrase (CAs) 18
2. CAs family 22
3. CA II and related disease 26
4. Inhibitors of CAs 28
II. Subject 30
1. Drug design 30
2. Results and discussions 34
2.1. Synthesis 34
2.2. Structure-activity relationship (SAR) study about results of in vitro inhibition assay 36
2.3. Docking study 41
III. Conclusion 45
IV. Experimental 46
V. Reference 59
APPENDICES 62
ABSTRACT IN KOREAN 77
Table 1. Classification by isoforms 24
Table 2. Related various diseases and possible off-targets... 27
Table 3. In vitro carbonic anhydrase inhibition assay of compounds 3a-k 39
Table 4. In vitro carbonic anhydrase inhibition assay of compounds 6a-k 40
Figure 1. Carbon dioxide transport in blood 20
Figure 2. The catalytic reaction of carbonic anhydrase in active site... 21
Figure 3. Schematic illustration of domain composition and... 25
Figure 4. Inhibitors of carbonic anhydrase 28
Figure 5. Role of each section for common structure of... 30
Figure 6. Normal type of CA II inhibitor linker 31
Figure 7. Strategies of targeting CA II 32
Figure 8. Binding mode of acetazolamide in active site (A)Zoom... 33
Figure 9. Active site residues of each isoenzyme. (A) Active site of... 43
Figure 10. Predicted molecular docking results of 3f and 6f (PDB... 44
Scheme 1. Synthesis of meta-substituted benzenesulfonamide... 35
Scheme 2. Synthesis of para-substituted benzenesulfonamide... 35
Spectrum H-1. ¹H NMR (500MHz, DMSO-d6) of compound 3a[이미지참조] 62
Spectrum H-2. ¹H NMR (500MHz, DMSO-d6) of compound 3b[이미지참조] 62
Spectrum H-3. ¹H NMR (500MHz, DMSO-d6) of compound 3c[이미지참조] 63
Spectrum H-4. ¹H NMR (500MHz, DMSO-d6) of compound 3d[이미지참조] 63
Spectrum H-5. ¹H NMR (500MHz, DMSO-d6) of compound 3e[이미지참조] 63
Spectrum H-6. ¹H NMR (500MHz, DMSO-d6) of compound 3f[이미지참조] 64
Spectrum H-7. ¹H NMR (500MHz, DMSO-d6) of compound 3g[이미지참조] 64
Spectrum H-8. ¹H NMR (500MHz, DMSO-d6) of compound 3h[이미지참조] 64
Spectrum H-9. ¹H NMR (500MHz, DMSO-d6) of compound 3i[이미지참조] 65
Spectrum H-10. ¹H NMR (500MHz, DMSO-d6) of compound 3j[이미지참조] 65
Spectrum H-11. ¹H NMR (500MHz, DMSO-d6) of compound 3k[이미지참조] 65
Spectrum H-12. ¹H NMR (500MHz, DMSO-d6) of compound 6a[이미지참조] 66
Spectrum H-13. ¹H NMR (500MHz, DMSO-d6) of compound 6b[이미지참조] 66
Spectrum H-14. ¹H NMR (500MHz, DMSO-d6) of compound 6c[이미지참조] 66
Spectrum H-15. ¹H NMR (500MHz, DMSO) of compound 6d[이미지참조] 67
Spectrum H-16. ¹H NMR (500MHz, DMSO) of compound 6e[이미지참조] 67
Spectrum H-17. ¹H NMR (500MHz, DMSO-d6) of compound 6f[이미지참조] 67
Spectrum H-18. ¹H NMR (500MHz, DMSO-d6) of compound 6g[이미지참조] 68
Spectrum H-19. ¹H NMR (500MHz, DMSO-d6) of compound 6h[이미지참조] 68
Spectrum H-20. ¹H NMR (500MHz, DMSO-d6) of compound 6i[이미지참조] 68
Spectrum H-21. ¹H NMR (500MHz, DMSO-d6) of compound 6j[이미지참조] 69
Spectrum H-22. ¹H NMR (500MHz, DMSO-d6) of compound 6k[이미지참조] 69
Spectrum C-1. ¹³C NMR (125MHz, DMSO-d6) of compound 3a[이미지참조] 69
Spectrum C-2. ¹³C NMR (125MHz, DMSO-d6) of compound 3b[이미지참조] 70
Spectrum C-3. ¹³C NMR (125MHz, DMSO-d6) of compound 3c[이미지참조] 70
Spectrum C-4. ¹³C NMR (125MHz, DMSO-d6) of compound 3d[이미지참조] 70
Spectrum C-5. ¹³C NMR (125MHz, DMSO-d6) of compound 3e[이미지참조] 71
Spectrum C-6. ¹³C NMR (125MHz, DMSO-d6) of compound 3f[이미지참조] 71
Spectrum C-7. ¹³C NMR (125MHz, DMSO-d6) of compound 3g[이미지참조] 71
Spectrum C-8. ¹³C NMR (125MHz, DMSO-d6) of compound 3h[이미지참조] 72
Spectrum C-9. ¹³C NMR (125MHz, DMSO-d6) of compound 3i[이미지참조] 72
Spectrum C-10. ¹³C NMR (125MHz, DMSO-d6) of compound 3j[이미지참조] 72
Spectrum C-11. ¹³C NMR (125MHz, DMSO-d6) of compound 3k[이미지참조] 73
Spectrum C-12. ¹³C NMR (125MHz, DMSO-d6) of compound 6a[이미지참조] 73
Spectrum C-13. ¹³C NMR (125MHz, DMSO-d6) of compound 6b[이미지참조] 73
Spectrum C-14. ¹³C NMR (125MHz, DMSO-d6) of compound 6c[이미지참조] 74
Spectrum C-15. ¹³C NMR (125MHz, DMSO-d6) of compound 6d[이미지참조] 74
Spectrum C-16. ¹³C NMR (125MHz, DMSO-d6) of compound 6e[이미지참조] 74
Spectrum C-17. ¹³C NMR (125MHz, DMSO-d6) of compound 6f[이미지참조] 75
Spectrum C-18. ¹³C NMR (125MHz, DMSO-d6) of compound 6g[이미지참조] 75
Spectrum C-19. ¹³C NMR (125MHz, DMSO-d6) of compound 6h[이미지참조] 75
Spectrum C-20. ¹³C NMR (125MHz, DMSO-d6) of compound 6i[이미지참조] 76
Spectrum C-21. ¹³C NMR (125MHz, DMSO-d6) of compound 6j[이미지참조] 76
Spectrum C-22. ¹³C NMR (125MHz, DMSO-d6) of compound 6k[이미지참조] 76