KR20110010634A - 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체를 포함하는 글루코코르티코이드 수용체 작용제 - Google Patents
치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체를 포함하는 글루코코르티코이드 수용체 작용제 Download PDFInfo
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- KR20110010634A KR20110010634A KR1020107027931A KR20107027931A KR20110010634A KR 20110010634 A KR20110010634 A KR 20110010634A KR 1020107027931 A KR1020107027931 A KR 1020107027931A KR 20107027931 A KR20107027931 A KR 20107027931A KR 20110010634 A KR20110010634 A KR 20110010634A
- Authority
- KR
- South Korea
- Prior art keywords
- trimethyl
- dihydroquinoline
- methoxy
- phenyl
- ylcarbonyloxy
- Prior art date
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- 229940124750 glucocorticoid receptor agonist Drugs 0.000 title claims abstract description 51
- JFUAWXPBHXKZGA-IBGZPJMESA-N 4-fluoro-2-[(4r)-5,5,5-trifluoro-4-hydroxy-2-methyl-4-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pentan-2-yl]phenol Chemical compound C([C@@](O)(CC=1NC2=CN=CC=C2C=1)C(F)(F)F)C(C)(C)C1=CC(F)=CC=C1O JFUAWXPBHXKZGA-IBGZPJMESA-N 0.000 title claims abstract description 26
- XKBGEVHKVFIMLY-UHFFFAOYSA-N 2,2,4-trimethyl-6-phenyl-1h-quinoline Chemical class C1=C2C(C)=CC(C)(C)NC2=CC=C1C1=CC=CC=C1 XKBGEVHKVFIMLY-UHFFFAOYSA-N 0.000 title abstract description 8
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 756
- 125000001424 substituent group Chemical group 0.000 claims abstract description 45
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 125000005843 halogen group Chemical group 0.000 claims abstract description 19
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 11
- -1 2-Chlorobenzoyloxy Chemical group 0.000 claims description 131
- 238000000034 method Methods 0.000 claims description 47
- 201000004624 Dermatitis Diseases 0.000 claims description 42
- 208000027866 inflammatory disease Diseases 0.000 claims description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 36
- 239000003814 drug Substances 0.000 claims description 34
- 230000000069 prophylactic effect Effects 0.000 claims description 25
- 229940124597 therapeutic agent Drugs 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 208000002780 macular degeneration Diseases 0.000 claims description 19
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 18
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 201000008937 atopic dermatitis Diseases 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 16
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 15
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 15
- 206010013774 Dry eye Diseases 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 15
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 14
- MIYGXFIBFAABCB-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] propane-1-sulfonate Chemical compound COC1=CC(OS(=O)(=O)CCC)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1CNC1=CC=CC=C1OC MIYGXFIBFAABCB-UHFFFAOYSA-N 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 9
- MSKLIAMYHIJSHE-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(2-methyl-5-nitrophenoxy)methyl]-1h-quinolin-6-yl]phenyl] pyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(C=2)[N+]([O-])=O)C)C(OC)=CC=1OC(=O)C1=CC=CN=C1 MSKLIAMYHIJSHE-UHFFFAOYSA-N 0.000 claims description 9
- ZQWMUCLWNLKPBT-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] morpholine-4-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)N3CCOCC3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 ZQWMUCLWNLKPBT-UHFFFAOYSA-N 0.000 claims description 9
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 8
- 201000011190 diabetic macular edema Diseases 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- COVBQWCPJSZFHY-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] morpholine-4-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)N1CCOCC1 COVBQWCPJSZFHY-UHFFFAOYSA-N 0.000 claims description 7
- VRXOYIJPPPTYID-UHFFFAOYSA-N [6-[2-methoxy-4-(2-methoxybenzoyl)oxyphenyl]-2,2,4-trimethyl-1h-quinolin-5-yl]methyl 5-methylthiophene-2-carboxylate Chemical compound COC1=CC=CC=C1C(=O)OC1=CC=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=C1 VRXOYIJPPPTYID-UHFFFAOYSA-N 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- PJYUDGDSEBLAIU-UHFFFAOYSA-N [3-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-4-methoxyphenyl] pyridine-3-carboxylate Chemical compound C1=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(F)C=2)C)C(OC)=CC=C1OC(=O)C1=CC=CN=C1 PJYUDGDSEBLAIU-UHFFFAOYSA-N 0.000 claims description 6
- ZCZVUUGAANFGKX-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] pyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CN=C1 ZCZVUUGAANFGKX-UHFFFAOYSA-N 0.000 claims description 6
- MNCIKIARUFHKGN-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] pyridine-3-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3C=NC=CC=3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 MNCIKIARUFHKGN-UHFFFAOYSA-N 0.000 claims description 6
- SHWGFMPNJCLOJQ-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] pyridine-4-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3C=CN=CC=3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 SHWGFMPNJCLOJQ-UHFFFAOYSA-N 0.000 claims description 6
- GQMFIXUQVVWKGE-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] n,n-dimethylcarbamate Chemical compound COC1=CC(OC(=O)N(C)C)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1COC1=CC(F)=CC=C1C GQMFIXUQVVWKGE-UHFFFAOYSA-N 0.000 claims description 6
- XBFZPNSSZKFTKC-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] propane-2-sulfonate Chemical compound COC1=CC(OS(=O)(=O)C(C)C)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1COC1=CC(F)=CC=C1C XBFZPNSSZKFTKC-UHFFFAOYSA-N 0.000 claims description 6
- MVRMNJHWHRKCJW-UHFFFAOYSA-N [6-[4-(2-chlorobenzoyl)oxy-2-methoxyphenyl]-2,2,4-trimethyl-1h-quinolin-5-yl]methyl 5-methylthiophene-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CC=C1Cl MVRMNJHWHRKCJW-UHFFFAOYSA-N 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 208000026278 immune system disease Diseases 0.000 claims description 6
- CYPFPZWYOVSNND-UHFFFAOYSA-N 3-o-[3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] 1-o-methyl benzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC=CC(C(=O)OC=2C=C(OC)C(=CC=2)C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)CNC=2C(=CC=CC=2)OC)=C1 CYPFPZWYOVSNND-UHFFFAOYSA-N 0.000 claims description 5
- WXHDURQQYXSQJK-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(2-methyl-5-nitrophenoxy)methyl]-1h-quinolin-6-yl]phenyl] n,n-dimethylcarbamate Chemical compound COC1=CC(OC(=O)N(C)C)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1COC1=CC([N+]([O-])=O)=CC=C1C WXHDURQQYXSQJK-UHFFFAOYSA-N 0.000 claims description 5
- NARMUGMVXIUQMJ-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] 1,3-thiazole-4-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CSC=N1 NARMUGMVXIUQMJ-UHFFFAOYSA-N 0.000 claims description 5
- LQXSLCUCYKJTDQ-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] 2-methoxypyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CN=C1OC LQXSLCUCYKJTDQ-UHFFFAOYSA-N 0.000 claims description 5
- JZMLROKBPNGWMT-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] 2-methylpyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CN=C1C JZMLROKBPNGWMT-UHFFFAOYSA-N 0.000 claims description 5
- DHDNRMSJHVAIMR-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] 3-methylfuran-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C=1OC=CC=1C DHDNRMSJHVAIMR-UHFFFAOYSA-N 0.000 claims description 5
- IHTYHBYTSDBHNM-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] 6-methylpyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=C(C)N=C1 IHTYHBYTSDBHNM-UHFFFAOYSA-N 0.000 claims description 5
- NMGGVEIYVVDIHL-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] furan-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C=1C=COC=1 NMGGVEIYVVDIHL-UHFFFAOYSA-N 0.000 claims description 5
- GIZUWOWXEQAHTG-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] morpholine-4-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)N1CCOCC1 GIZUWOWXEQAHTG-UHFFFAOYSA-N 0.000 claims description 5
- NLSFZQSFBMZTPN-UHFFFAOYSA-N [3-methoxy-4-[2,2,4-trimethyl-5-[(5-methylthiophene-2-carbonyl)oxymethyl]-1h-quinolin-6-yl]phenyl] pyridine-4-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=NC=C1 NLSFZQSFBMZTPN-UHFFFAOYSA-N 0.000 claims description 5
- POERGSQZEMSOJN-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxy-5-nitrophenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] thiophene-3-carboxylate Chemical compound COC1=CC=C([N+]([O-])=O)C=C1OCC1=C(C=2C(=CC(OC(=O)C3=CSC=C3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 POERGSQZEMSOJN-UHFFFAOYSA-N 0.000 claims description 5
- FDLDWJJDQMLCML-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] 2-methoxypyridine-3-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3C(=NC=CC=3)OC)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 FDLDWJJDQMLCML-UHFFFAOYSA-N 0.000 claims description 5
- FZLVALQWUJPDKI-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] 2-methylpyridine-3-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3C(=NC=CC=3)C)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 FZLVALQWUJPDKI-UHFFFAOYSA-N 0.000 claims description 5
- KBYUELDOSLOVBH-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] benzoate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3C=CC=CC=3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 KBYUELDOSLOVBH-UHFFFAOYSA-N 0.000 claims description 5
- APVJMXTVEFHGKX-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] furan-2-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3OC=CC=3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 APVJMXTVEFHGKX-UHFFFAOYSA-N 0.000 claims description 5
- SOSBJDLVERJQCQ-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] furan-3-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C3=COC=C3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 SOSBJDLVERJQCQ-UHFFFAOYSA-N 0.000 claims description 5
- UVDDSAGDMJRQKM-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxyanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] thiophene-2-carboxylate Chemical compound COC1=CC=CC=C1NCC1=C(C=2C(=CC(OC(=O)C=3SC=CC=3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 UVDDSAGDMJRQKM-UHFFFAOYSA-N 0.000 claims description 5
- OTRWGZUUJKPYHA-UHFFFAOYSA-N [3-methoxy-4-[5-[(4-methoxybenzoyl)oxymethyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] pyridine-3-carboxylate Chemical compound C1=CC(OC)=CC=C1C(=O)OCC1=C(C=2C(=CC(OC(=O)C=3C=NC=CC=3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 OTRWGZUUJKPYHA-UHFFFAOYSA-N 0.000 claims description 5
- OPYMCPHOVNKJJK-UHFFFAOYSA-N [4-[5-[(5-bromothiophene-2-carbonyl)oxymethyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] furan-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(Br)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CO1 OPYMCPHOVNKJJK-UHFFFAOYSA-N 0.000 claims description 5
- KIRUMWWSSPEAEQ-UHFFFAOYSA-N [4-[5-[(5-bromothiophene-2-carbonyl)oxymethyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] pyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(Br)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CN=C1 KIRUMWWSSPEAEQ-UHFFFAOYSA-N 0.000 claims description 5
- SIUHZCNHXMSKFP-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] 2-methoxypyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)CNC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=CN=C1OC SIUHZCNHXMSKFP-UHFFFAOYSA-N 0.000 claims description 5
- XBGFEIRYBTYBER-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] 2-methylpyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)CNC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=CN=C1C XBGFEIRYBTYBER-UHFFFAOYSA-N 0.000 claims description 5
- PTCAQLSKMAJKHR-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] 3-methylfuran-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)CNC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C=1OC=CC=1C PTCAQLSKMAJKHR-UHFFFAOYSA-N 0.000 claims description 5
- BQCNGDSUKMITQP-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylanilino)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] pyridine-4-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)CNC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=NC=C1 BQCNGDSUKMITQP-UHFFFAOYSA-N 0.000 claims description 5
- DTRXUPOYAPPEFM-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] n-[2-(dimethylamino)ethyl]-n-ethylcarbamate Chemical compound COC1=CC(OC(=O)N(CCN(C)C)CC)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1COC1=CC(F)=CC=C1C DTRXUPOYAPPEFM-UHFFFAOYSA-N 0.000 claims description 5
- UPJVLHVFNRZGNR-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] pyridine-3-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=CN=C1 UPJVLHVFNRZGNR-UHFFFAOYSA-N 0.000 claims description 5
- VYQLOCIJGGTOBS-UHFFFAOYSA-N [6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1h-quinolin-5-yl]methyl 5-methylthiophene-2-carboxylate Chemical compound COC1=CC(OS(=O)(=O)CCC)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1COC(=O)C1=CC=C(C)S1 VYQLOCIJGGTOBS-UHFFFAOYSA-N 0.000 claims description 5
- ACYOMMYDCFDNRU-UHFFFAOYSA-N [6-(4-benzoyloxy-2-methoxyphenyl)-2,2,4-trimethyl-1h-quinolin-5-yl]methyl 5-methylthiophene-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=CC=C1 ACYOMMYDCFDNRU-UHFFFAOYSA-N 0.000 claims description 5
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- XGGSAIQPWMLKDL-UHFFFAOYSA-N [3-methoxy-4-[5-[(2-methoxy-5-nitrophenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]phenyl] cyclopropanesulfonate Chemical compound COC1=CC=C([N+]([O-])=O)C=C1OCC1=C(C=2C(=CC(OS(=O)(=O)C3CC3)=CC=2)OC)C=CC2=C1C(C)=CC(C)(C)N2 XGGSAIQPWMLKDL-UHFFFAOYSA-N 0.000 claims description 3
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- UCDWKEWGRJHSHN-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] 2,2-dimethylpropanoate Chemical compound COC1=CC(OC(=O)C(C)(C)C)=CC=C1C1=CC=C(NC(C)(C)C=C2C)C2=C1COC1=CC(F)=CC=C1C UCDWKEWGRJHSHN-UHFFFAOYSA-N 0.000 claims description 3
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- YBIGGGDFXNMGJZ-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] 5-methylfuran-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=C(C)O1 YBIGGGDFXNMGJZ-UHFFFAOYSA-N 0.000 claims description 3
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- MQHGWZXZNWRXRE-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] furan-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=CO1 MQHGWZXZNWRXRE-UHFFFAOYSA-N 0.000 claims description 3
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- QTYOCUDKASYSHN-UHFFFAOYSA-N [4-[5-[(5-fluoro-2-methylphenoxy)methyl]-2,2,4-trimethyl-1h-quinolin-6-yl]-3-methoxyphenyl] pyridine-4-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC=2C(=CC=C(F)C=2)C)C(OC)=CC=1OC(=O)C1=CC=NC=C1 QTYOCUDKASYSHN-UHFFFAOYSA-N 0.000 claims description 3
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- BSBNNJHDSWXFHP-UHFFFAOYSA-N [6-[4-(4-fluorobenzoyl)oxy-2-methoxyphenyl]-2,2,4-trimethyl-1h-quinolin-5-yl]methyl 5-methylthiophene-2-carboxylate Chemical compound C=1C=C(C=2C(=C3C(C)=CC(C)(C)NC3=CC=2)COC(=O)C=2SC(C)=CC=2)C(OC)=CC=1OC(=O)C1=CC=C(F)C=C1 BSBNNJHDSWXFHP-UHFFFAOYSA-N 0.000 claims description 3
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 522
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Abstract
본 발명은 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체인, 하기 일반식 (1)로 표시되는 화합물 또는 그 염을 포함하는 글루코코르티코이드 수용체 작용제 및 상기 작용제의 새로운 약리 작용에 관한 것이다. 식 (1)에서, R1은 식 (2a), (3a), (4a) 또는 (5a)를, R2는 -(CO)-R8, -(CO)O-R9 등을, R2-O-는 벤젠환 A의 4 또는 5번 위치에서 치환되고, R3는 저급 알킬기를, R4, R5, R6 또는 R7은 할로겐 원자, 치환기를 가질 수 있는 저급 알킬기 등을, m, n, p 또는 q는, 0, 1 등을, R8, R9 등은 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기 등을 나타낸다:
Description
본 발명은 의약으로서 유용한 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체를 포함하는 글루코코르티코이드 수용체 작용제에 관한 것이다. 본 발명의 글루코코르티코이드 수용체 작용제는 염증성 질환 또는 면역 질환의 예방 또는 치료제, 특히 안염증성 질환 또는 피부염의 예방 또는 치료제로서 유용하다.
글루코코르티코이드 수용체는, 핵 내 수용체 슈퍼패밀리에 속하는 94 kDa의 리간드 활성화 세포내 전사 조절 요소이다. 이 수용체는, 그 전사 조절 작용에 의해, 탄수화물, 단백질, 지방 등의 대사조절, 면역 염증반응의 억제, 중추신경계의 활성화, 심혈관계 기능의 조절, 기초·스트레스 관련 항상성 등에 영향을 미치는 것으로 알려져 있다. (비특허 문헌 1, 특허 문헌 1).
이 글루코코르티코이드 수용체와 결합하는 약물은, 글루코코르티코이드 수용체 작용제 작용 또는 글루코코르티코이드 수용체 길항체 작용을 가진다. 그러나, 이들 작용은 전혀 상이한 것이므로, 약물의 미세한 화학 구조의 차이에 따라 어느쪽의 작용을 나타내는지가 결정된다.
대표적인 글루코코르티코이드 수용체 작용제로서는, 코르티솔, 코르티코스테론 등의 생체 내에서 만들어지는 글루코코르티코이드 수용체 작용제나 덱사메타손, 프레드니손, 프레드니솔론 등의 합성 글루코코르티코이드 수용체 작용제가 알려져 있다(특허 문헌 1). 이들 글루코코르티코이드 수용체 작용제는, 스테로이드 구조를 가지는 때문에, 총칭하여 스테로이드류로 호칭되고 있으며 각종 질환의 치료에 응용되고 있다.
그러나, 이들 스테로이드류는, 그 사용에 따라 스테로이드 소화성 궤양, 스테로이드 자반병(purpura), 스테로이드 췌염, 스테로이드 당뇨병, 스테로이드 백내장, 스테로이드 녹내장 등의 부작용을 발현하는 경우가 있다 (비특허 문헌 2). 따라서, 이들 부작용을 회피하기 위해, 스테로이드 구조를 갖지 않는 약제의 개발이 필요되고 있다.
한편, 1, 2-디하이드로퀴놀린 구조를 가지는 화합물이, 스테로이드 수용체 조절제로서 특허 문헌 2, 특허 문헌 3, 특허 문헌 4 등에 개시되어 있다. 특허 문헌 2, 특허 문헌 3 및 특허 문헌 4에 개시되어 있는 화합물은, 매우 광범위하고, 각종 화학 구조를 가지고 있으며, 그 중 하나로서 1, 2-디하이드로퀴놀린 구조의 화합물이 개시되어 있다. 그러나, 이들 가운데 어떠한 화학 구조의 화합물이 글루코코르티코이드 수용체 작용제 활성을 가지는지, 즉 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체가 글루코코르티코이드 수용체 작용제 활성을 가지는지에 관한 구체적인 개시는 전혀 되어 있지 않다.
[비특허 문헌 1] 종합 임상, 54(7),1951-2076(2005)
[비특허 문헌 2] 남산당 의학대사전 제17판, 1038-1040면
치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체의 새로운 약리 작용을 발견한 것은 매우 흥미로운 과제이다.
그래서, 본 발명자 등은 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체의 새로운 약리 작용을 발견하고 예의 연구한 결과, 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체가 글루코코르티코이드 수용체에 대하여, 우수한 작용제 활성을 가지고, 염증성 질환의 예방 또는 치료제로서 유용하다는 것을 발견하였다.
또한, 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체를 안염증성 질환 모델(마우스 알레르기성 결막염 모델, 래트 맥락막 혈관 신생 모델 또는 래트 각막 장해 모델)에 점안 투여한 결과, 이들 질환 모델에 대하여, 우수한 억제 효과(각각 혈관 투과성 항진 저해 효과, 맥락막 혈관 신생 저해 효과, 각막 장해 개선 효과)가 인정되었다.
또한, 이 유도체는, 마우스 아토피성 피부염 모델에 있어서도, 우수한 혈관 투과성 항진 저해 효과가 인정되어, 이 유도체가 안염증성 질환 또는 피부염의 예방 또는 치료제로서 특히 유용하다는 것을 발견하고, 본 발명을 완성하였다.
본 발명에 있어서 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체란, 하기 일반식 (1)로 표시되는 화합물 또는 그 염(이하, 「본 화합물」이라고 함)을 의미하며, 본 발명은, 본 화합물을 포함하는 글루코코르티코이드 수용체 작용제 및 상기 글루코코르티코이드 수용체 작용제 중 적어도 하나를 유효 성분으로서 함유하는 의약 조성물에 관한 것이고, 바람직하게는, 상기 글루코코르티코이드 수용체 작용제 중 적어도 하나를 유효 성분으로서 함유하는 염증성 질환의 예방 또는 치료제, 더욱 바람직하게는, 상기 글루코코르티코이드 수용체 작용제 중 적어도 하나를 유효 성분으로서 함유하는 안염증성 질환 또는 피부염의 예방 또는 치료제에 관한 것이다.
[R1은 하기 일반식 (2a), (3a), (4a) 또는 (5a)를 나타내고;
R2는 -(CO)-R8, -(CO)O-R9, -(SO)-R10, -(SO2)-R11 또는 -(CO)NR12R13을 나타내고;
R2-O-는, 벤젠환 A의 4 또는 5번 위치에서 치환되고;
R3는 저급 알킬기를 나타내고;
R4, R5, R6 또는 R7은, 할로겐 원자, 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 알키닐기, 저급 알콕시기, 니트로기 또는 포르밀기를 나타내고;
m, n, p 또는 q는, 0, 1 또는 2를 나타내고;
m, n, p 또는 q가 2를 나타내는 경우, 각 R4, R5, R6 또는 R7은 동일 또는 상이해도 되고;
R8, R9, R10 또는 R11은, 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 시클로알킬기, 치환기를 가질 수 있는 아릴기 또는 치환기를 가질 수 있는 복소환기를 나타내고;
R12 및 R13은 동일 또는 상이해도 되며, 수소 원자, 치환기를 가질 수 있는 저급 알킬기, 치환기를 가질 수 있는 아릴기 또는 복소환기를 나타낸다. 이하, 동일함.]
본 명세서에서 사용되는 용어 및 구문(원자, 기 등)의 정의에 대하여 이하 상세하게 설명한다. 또한, 이하의 용어 및 구문의 정의가 다른 용어 및 구문의 정의에 준용되는 경우, 각 정의의 바람직한 범위 및 특히 바람직한 범위도 준용한다.
「할로겐 원자」란, 불소, 염소, 브롬 또는 요오드 원자를 의미한다.
「저급 알킬기」란, 탄소 원자수가 1∼8개, 바람직하게는 1∼6개인 직쇄 또는 분지의 알킬기를 의미한다.
구체예로서,메틸, 에틸, n-프로필, n-부틸, n-펜틸, n-헥실, n-헵틸, n-옥틸, 이소프로필, 이소부틸, sec-부틸, tert-부틸, 이소펜틸기 등을 들 수 있다.
「저급 알케닐기」란, 탄소 원자수가 2∼8개, 바람직하게는 2∼6개인 직쇄 또는 분지의 알케닐기를 의미한다. 구체예로서, 비닐, 프로페닐, 부테닐, 펜테닐, 헥세닐, 헵테닐, 옥테닐, 이소프로페닐, 2-메틸-1-프로페닐, 2-메틸-2-부테닐기 등을 들 수 있다.
「저급 알키닐기」란, 탄소 원자수가 2∼8개, 바람직하게는 2∼6개인 직쇄 또는 분지의 알키닐기를 의미한다. 구체예로서, 에티닐, 프로피닐, 브티닐, 펜티닐, 헥시닐, 헵티닐, 옥티닐, 이소부티닐, 이소펜티닐기 등을 들 수 있다.
「저급 시클로알킬기」란, 탄소 원자수가 3∼10개, 바람직하게는 3∼8개인 시클로알킬기를 의미한다. 구체예로서, 시클로프로필, 시클로부틸, 시클로펜틸, 시클로헥실, 시클로헵틸, 시클로옥틸, 시클로노나닐 또는 시클로데카닐기를 들 수 있다.
「아릴기」란, 탄소 원자수가 6∼14개인 단환식 방향족 탄화수소기 또는 2환식 또는 3환식의 축합 다환식 방향족 탄화수소기로부터 수소 1 원자를 제외한 잔기를 의미한다. 구체예로서, 페닐, 나프틸, 안트릴, 페난트릴기 등을 들 수 있고, 특히 페닐이 바람직하다.
「복소환」이란, 질소 원자, 산소 원자 및 황 원자로부터 선택되는 1 또는 복수 개의 헤테로원자를 환 내에 가지는 포화 또는 불포화 단환식 복소환(바람직하게는, 1 또는 2개의 헤테로 원자를 환 내에 가지는, 탄소 원자수 3∼5개의 포화 또는 불포화 단환식 5 또는 6원 복소환) 또는 2환식 또는 3환식의 축합 다환식 복소환(바람직하게는, 1 또는 2개의 헤테로원자를 환 내에 가지는, 탄소 원자수 7∼13개의 2환식 또는 3환식의 축합 다환식 복소환)을 의미한다.
「포화 단환식 복소환」의 구체예로서, 질소 원자를 환 내에 가지는 피롤리딘, 피라졸리딘, 이미다졸리딘, 트리아졸리딘, 피페리딘, 헥사하이드로피리다진, 헥사하이드로피리미딘, 피페라진, 호모피페리딘, 호모피페라진 환 등이, 산소 원자를 환 내에 가지는 테트라하이드로퓨란, 테트라하이드로피란 환 등이, 황 원자를 환 내에 가지는 테트라하이드로티오펜, 테트라하이드로티오피란 환 등이, 질소 원자와 산소 원자를 환 내에 가지는 옥사졸리딘, 이소옥사졸리딘, 모르폴린 환 등이, 질소 원자와 황 원자를 환 내에 가지는 티아졸리딘, 이소티아졸리딘, 티오모르폴린 환 등을 들 수 있다.
또한, 이들 포화 단환식 복소환은 벤젠환 등과 축합하여 디하이드로인돌, 디하이드로인다졸, 디하이드로벤즈이미다졸, 테트라하이드로퀴놀린, 테트라하이드로이소퀴놀린, 테트라하이드로시놀린, 테트라하이드로프탈라진, 테트라하이드로퀴나졸린, 테트라하이드로퀴녹살린, 디하이드로벤조퓨란, 디하이드로이소벤조퓨란, 크로만, 이소크로만, 디하이드로벤조티오펜, 디하이드로이소벤조티오펜, 티오크로만, 이소티오크로만, 디하이드로벤조옥사졸, 디하이드로벤즈이소옥사졸, 디하이드로벤즈옥사진, 디하이드로벤조티아졸, 디하이드로벤즈이소티아졸, 디하이드로벤조티아진, 크산텐, 4a-카르바졸, 페리미딘 환 등의 2환식 또는 3환식의 축합 다환식 복소환을 형성해도 된다.
「불포화 단환식 복소환」의 구체예로서, 질소 원자를 환 내에 가지는 디하이드로피롤, 피롤, 디하이드로피라졸, 피라졸, 디하이드로이미다졸, 이미다졸, 디하이드로트리아졸, 트리아졸, 테트라하이드로피리딘, 디하이드로피리딘, 피리딘, 테트라하이드로피리다진, 디하이드로피리다진, 피리다진, 테트라하이드로피리미딘, 디하이드로피리미딘, 피리미딘, 테트라하이드로피라진, 디하이드로피라진, 피라진 환 등이, 산소 원자를 환 내에 가지는 디하이드로퓨란, 퓨란, 디하이드로피란, 피란 환 등이, 황 원자를 환 내에 가지는 디하이드로티오펜, 티오펜, 디하이드로티오피란, 티오피란 환 등이, 질소 원자와 산소 원자를 환 내에 가지는 디하이드로옥사졸, 옥사졸, 디하이드로이소옥사졸, 이소옥사졸, 디하이드로옥사진, 옥사진 환 등이, 질소 원자와 황 원자를 환 내에 가지는 디하이드로티아졸, 티아졸, 디하이드로이소티아졸, 이소티아졸, 디하이드로티아진, 티아진 환 등을 들 수 있다.
또한, 이들 불포화 단환식 복소환은 벤젠환 등과 축합하여 인돌, 인다졸, 벤즈이미다졸, 벤조트리아졸, 디하이드로퀴놀린, 퀴놀린, 디하이드로이소퀴놀린, 이소퀴놀린, 페난트리딘, 디하이드로시놀린, 시놀린, 디하이드로프탈라진, 프탈라진, 디하이드로퀴나졸린, 퀴나졸린, 디하이드로퀴녹살린, 퀴녹살린, 벤조퓨란, 이소벤조퓨란, 크로멘, 이소크로멘, 벤조티오펜, 이소벤조티오펜, 티오크로멘, 이소티오크로멘, 벤즈옥사졸, 벤즈이속사졸, 벤즈옥사진, 벤조티아졸, 벤즈이소티아졸, 벤조티아진, 페녹산틴, 카르바졸, β-카르볼린, 페난트리딘, 아크리딘, 페난트롤린, 페나진, 페노티아진, 페녹사진 환 등의 2환식 또는 3환식의 축합 다환식 복소환을 형성해도 된다.
그리고, 전술한 「복소환」중, 피페리딘, 모르폴린, 이미다졸, 피리딘, 피리미딘, 퓨란, 티오펜, 옥사졸 또는 티아졸 환이 바람직하다.
「복소환기」란, 상기 복소환으로부터 수소 1 원자를 제외한 잔기를 의미한다.
「저급 알콕시기」란, 하이드록시기의 수소 원자가 저급 알킬기로 치환된 기를 의미한다. 구체예로서, 메톡시, 에톡시, n-프로폭시, n-부톡시, n-펜톡시, n-헥실옥시, n-헵틸옥시, n-옥틸옥시, 이소프로폭시, 이소부톡시, sec-부톡시, tert-부톡시, 이소펜톡시 기 등을 들 수 있다.
「저급 알킬티오기」란, 메르캅토기의 수소 원자가 저급 알킬기로 치환된 기를 의미한다. 구체예로서, 메틸티오, 에틸티오, n-프로필티오, n-부틸티오, n-펜틸티오, n-헥실티오, n-헵틸티오, n-옥틸티오, 이소프로필티오, 이소부틸티오, sec-부틸티오, tert-부틸티오, 이소펜틸티오 기 등을 들 수 있다.
「저급 알킬카르보닐기」란, 포르밀기의 수소 원자가 저급 알킬기로 치환된 기를 의미한다. 구체예로서 메틸카르보닐, 에틸카르보닐, n-프로필카르보닐, n-부틸카르보닐, n-펜틸카르보닐, n-헥실카르보닐, n-헵틸카르보닐, n-옥틸카르보닐, 이소프로필카르보닐, 이소부틸카르보닐, sec-부틸카르보닐, tert-부틸카르보닐, 이소펜틸카르보닐 기 등을 들 수 있다.
「저급 알콕시카르보닐기」란, 포르밀기의 수소 원자가 저급 알콕시기로 치환된 기를 의미한다. 구체예로서, 메톡시카르보닐, 에톡시카르보닐, n-프로폭시카르보닐, n-부톡시카르보닐, n-펜톡시카르보닐, n-헥실옥시카르보닐, n-헵틸옥시카르보닐, n-옥틸옥시카르보닐, 이소프로폭시카르보닐, 이소부톡시카르보닐, sec-부톡시카르보닐, tert-부톡시카르보닐, 이소펜톡시카르보닐 기 등을 들 수 있다.
「저급 알킬카르보닐옥시기」란, 하이드록시기의 수소 원자가 저급 알킬카르보닐기로 치환된 기를 의미한다. 구체예로서 메틸카르보닐옥시, 에틸카르보닐옥시, n-프로필카르보닐옥시, n-부틸카르보닐옥시, n-펜틸카르보닐옥시, n-헥실카르보닐옥시, n-헵틸카르보닐옥시, n-옥틸카르보닐옥시, 이소프로필카르보닐옥시, 이소부틸카르보닐옥시, sec-부틸카르보닐옥시, tert-부틸카르보닐옥시, 이소펜틸카르보닐옥시 기 등을 들 수 있다.
「치환기를 가질 수 있는 저급 알킬기」란, 하기 α1군으로부터 선택되는 1 또는 복수 개의 치환기를 가질 수 있는, 바람직하게는 α2군으로부터 선택되는 1 또는 복수 개의 치환기를 가질 수 있는 「저급 알킬기」를 의미한다.
[α1군]
할로겐 원자, 저급 시클로알킬기, 아릴기, 복소환기, 저급 알콕시기 및 -NRaRb.
[α2군]
할로겐 원자, 아릴기, 복소환기, 저급 알콕시기 및 -NRaRb.
「치환기를 가질 수 있는 아릴기」 및/또는 「치환기를 가질 수 있는 복소환기」란, 하기 β1군으로부터 선택되는 1 또는 복수 개의 치환기를 가질 수 있는, 바람직하게는 β2군으로부터 선택되는 1 또는 복수 개의 치환기를 가질 수 있는 「아릴기」 및/또는 「복소환기」를 의미한다.
[β1군]
할로겐 원자, 저급 알킬기, 하이드록시기, 저급 알콕시기, 메르캅토기, 저급 알킬티오기, 포르밀기, 저급 알킬카르보닐기, 카르복시기, 저급 알콕시카르보닐기, 저급 알킬카르보닐옥시기, 니트로기 및 시아노기.
[β2군]
할로겐 원자, 저급 알킬기, 저급 알콕시기, 저급 알킬티오기, 저급 알킬카르보닐기, 저급 알콕시카르보닐기, 저급 알킬카르보닐옥시기, 니트로기 및 시아노기.
그리고, 상기 「-NRaRb」의 Ra 및 Rb는, 동일 또는 상이할 수 있고, 하기 γ1군으로부터 선택되는 치환기를, 바람직하게는 γ2군으로부터 선택되는 치환기를 의미한다.
[γ1군]
수소 원자, 저급 알킬기 및 저급 알콕시카르보닐기.
[γ2군]
수소 원자 및 저급 알킬기.
본 발명에서 말하는 「복수 개의 기」란, 각각의 기가 동일 또는 상이해도 되고, 치환하는 부위에 있어서 2개 이상, 치환될 수 있는 기의 수 이하의 개수의 기를 나타내고, 그 개수는 2 또는 3개의 경우가 바람직하고, 2개인 경우가 특히 바람직하다.
또한, 본 발명에 있어서, 수소 원자나 할로겐 원자도 「기」의 개념에 포함된다.
본 발명에 있어서 「글루코코르티코이드 수용체 작용제」란, 글루코코르티코이드 수용체와 결합함으로써, 완전 작용제 기능 또는 부분 작용제 기능을 발현하는 것을 의미한다.
본 발명에 있어서 「예방 또는 치료제」란, 질병의 예방 및/또는 치료를 위한 약제를 의미한다.
또한, 본 발명의 「글루코코르티코이드 수용체 작용제」의 의약 용도로서는, 글루코코르티코이드 수용체 작용제로 예방 또는 치료 가능한 질환이면, 특별히 제한되지 않으며, 통상, 당질 스테로이드류로 치료 가능한 모든 질환에 적용할 수 있다.
예를 들면, 만성 부신피질 기능부전(원발성, 연발성, 뇌하수체성, 의원성), 급성 부신피질 기능부전(부신 위기), 부신성기 증후군, 아급성 갑상선염, 갑상선 중독증[갑상선 (중독성) 위기], 갑상선 질환에 따른 악성 안구 돌출증, ACTH 단독 결손증, 특발성 저혈당증 등의 내분비 질환; 홍반루푸스(전신성 및 만성 원판형), 전신성 혈관염(대동맥염 증후군, 결절성 동맥 주위염, 다발성 동맥염, 베게너 육아종증을 포함함), 다발성 근육염증(피부 근육염증), 강피증 등의 교원병; 신증, 신증후군 등의 신장 질환; 울혈성 심부전 등의 심장 질환; 기관지 천식, 천식성 기관지염(소아 천식성 기관지염을 포함함), 약제 또는 그 외의 화학물질에 의한 알레르기, 독소(약진, 중독발진을 포함함), 혈청병 등의 알레르기성 질환; 자반병(혈소판 감소성 및 혈소판 비감소성), 재생불량성 빈혈, 백혈병(급성 백혈병, 만성 골수성 백혈병의 급성 전환, 만성 림프액성 백혈병, 피부 백혈병을 포함함), 용혈성 빈혈, 과립구 감소증 등의 혈액 질환; 궤양성 대장염, 국소성 장염, 중증 소모성 질환의 전신 상태의 개선(암 말기, 스프루를 포함함) 등의 소화기 질환; 전격성 간염, 담즙 정체형 급성 간염, 만성 간염, 간경변 등의 간질환; 사르코이드증, 미만성 간질성 폐렴(폐선유증, 방사선 폐장염을 포함함) 등의 폐질환; 중증 감염증; 폐결핵, 결핵성 수막염, 결핵성 흉막염, 결핵성 복막염, 결핵성 심염 등의 결핵성 질환; 뇌척수염(뇌염, 척수염을 포함함), 말초 신경염(길랭-바레 증후군을 포함함), 근강직증, 중증근무력증, 다발성 경화증(시신경척수염을 포함함), 소무도병, 안면 신경 마비, 척수 지주막 망막염 등의 신경 질환; 악성 림프종(림프액 육종증, 세망 육종증, 호지킨병, 피부세망증, 균상식육종) 및 유사 질환(근친 질환), 호산성 육아종, 유방암의 재발 전이 등의 악성 종양; 항악성종양제(시스플라틴 등) 투여에 따른 소화기 증상(구역, 구토); 부신 절제, 부신피질 기능부전 환자에 대한 외과적 침습, 침습 후 폐수종, 장기·조직 이식, 뱀독·곤충독(중증의 벌레에 찔리는 것을 포함함), 원인 불명의 발열 등의 외과 질환; 난관 정형 수술 후 유착 방지 등의 산부인과 질환; 전립선암, 음경지속발기증 등의 비뇨기과질환; 급성·만성 중이염, 삼출성 중이염·이관협착증, 메니에르 병 및 메니에르 증후군, 급성 감음성 난청, 혈관 운동(신경)성 비염, 알레르기성 비염, 꽃가루 알레르기(고초열), 진행성 회저성 비염, 후두염·후두 부종, 이비인후과 영역의 수술 후의 후속 치료, 후각 장해, 급성·만성(반복성) 침샘염 등의 이비인후과 질환; 난치성 구내염 및 설염 등의 구강외과 질환; 류머티스성 열(류머티스성 심염을 포함함), 류머티스성 다발근통, 경직성 척추염(류머티스성 척추염) 등의 류머티스성 질환, 하기 염증성 질환 등을 들 수 있다.
본 발명에서 말하는 「염증성 질환」이란, 염증을 수반하는 질환이면, 특별히 제한되지 않는다.
예를 들면, 염증성 골·관절 질환, 안염증성 질환, 천식, 기관지염, 비염, 피부염, 염증성장질환 등을 들 수 있고, 바람직하게는, 염증성 골·관절 질환, 안염증성 질환, 피부염을 들 수 있다.
이 때, 「염증성 골·관절 질환」이란, 관절부에 있어서 염증을 수반하는 질환이면, 특별히 제한되지 않는다. 예를 들면, 관절 류머티즘, 청년성 관절 류머티즘(스틸 병을 포함함) 변형성 관절증, 골다공증, 척추 관절염 등을 들 수 있고, 바람직하게는 관절 류머티즘 또는 변형성 관절증을 들 수 있다.
또한, 「안염증성 질환」이란, 안부에 있어서 염증을 수반하는 질환이면, 특별히 제한되지 않는다. 예를 들면, 전안부 염증성 질환으로서, 각막염, 각결막염, 결막염, 안검염, 안구 건조 증후군(「건성안」이라고도 함), 알레르기성 결막염, 앞부분 포도막염, 전안부의 수술 후 염증, 눈 조직 이식 거부반응에 의한 염증 등이, 바람직하게는, 안구 건조 증후군(「건성안」이라고도 함) 또는 알레르기성 결막염을 들 수 있다. 또한, 후안부 염증성 질환으로서, 연령관련 황반변성(초기 연령관련 황반변성, 위축형 연령관련 황반변성 및/또는 삼출형 연령관련 황반변성), 당뇨성 망막증, 당뇨성 황반부종, 혈관신생 황반증, 돌발성 황반상막, 증식성 유리체 망막증, 망막색소 변성증, 망막 중심 정맥 폐색증, 망막 중심 동맥 폐색증, 망막정맥 분지 폐색증, 망막동맥 분지 폐색증, 망막박리나 외상에 의한 염증이나 변성, 후안부의 수술 후 염증, 망막염, 포도막염, 공막염, 시신경염 등이, 바람직하게는, 연령관련 황반변성(초기 연령관련 황반변성, 위축형 연령관련 황반변성 및/또는 삼출형 연령관련 황반변성), 당뇨성 망막증, 당뇨성 황반부종, 혈관신생 황반증, 돌발성 황반상막, 증식성 유리체 망막증, 망막색소 변성증, 망막 중심 정맥 폐색증, 망막 중심 동맥 폐색증, 망막정맥 분지 폐색증, 망막동맥 분지 폐색증, 망막박리나 외상에 의한 염증이나 변성, 망막염 등의 망막질환이, 특히 바람직하게는, 연령관련 황반변성, 당뇨성 망막증 또는 당뇨성 황반부종을 들 수 있다.
또한, 「피부염」이란, 피부에 있어서 염증을 수반하는 질환이면, 특별히 제한되지 않는다. 예를 들면, 습진·피부염 군(급성 습진, 아급성 습진, 만성 습진, 접촉 피부염, 화폐상 습진, 자가 감작성 피부염, 아토피성 피부염, 유·유·소아 습진, 비달태선(lichen simplex chronicus vidal), 그 외의 신경피부염, 지방과다분비성 피부염, 진행성 지장 각피증(keratodermia tylodes Palmaris progressiva), 그 외의 손가락의 피부염, 음부 또는 항문 습진, 귓바퀴 및 외이도의 습진·피부염, 코 전정 및 비익 주변의 습진·피부염 등), 양진 군(소아 스트로플루스, 담마진 양태선, 고정 두드러기를 포함함), 두드러기, 유사건선 및 유사건선 (심상성 건선(중증예), 관절증성 건선, 건선성 홍피증, 농포성 건선, 계류성 말단 피부염, 포진상 농가진, 라이터 증후군), 수장족저 농포증, 편평태선, 성년성 부종성 경화증, 홍반(다형삼출성 홍반, 결절성 홍반), 아나필락시스 자반병(단순형, 쉐라인형, 헤노호형), 웨버 크리스찬병, 점막 피부안 증후군(개구부 미란성 외피증, 스티븐스 ·존슨병, 피부 구내염, 퍽스 증후군, 베체트증, 립슈츠 급성 음문 궤양), 레이노병, 원형 탈모증, 천포창 군(심상성 천포창, 낙엽성 천포창, 세니어-어셔 증후군, 증식성 천포창), 듀링(Duhring) 포진장 피부염(유사 천포창, 임신성 포진을 포함함), 선천성 표피 수포증, 대상포진, 홍피증(헤브라 홍색비강진을 포함함), 안면 파종상 조립성 낭창(lupus miliaris disseminatus faciei), 알레르기성 혈관염 및 그 유사증(급성 태선모양 잔비늘증을 포함함), 궤양성 만성 농피증, 신생아 피부경화 등의 피부과 질환이, 바람직하게는, 습진·피부염 군, 양진 군, 두드러기, 건선 및 유사건선 또는 아토피성 피부염이, 특히 바람직하게는 아토피성 피부염을 들 수 있다.
본 발명에서 말하는 「면역 질환」이란, 면역이 관여하는 질환이면, 특별히 제한은 없으나, 특히 「자가면역질환」을 들 수 있다.
본 화합물에 있어서의 「염」이란, 의약으로서 허용되는 염이면, 특별히 제한은 없으며, 염산, 브롬화수소산, 요오드화수소산, 질산, 황산, 인산 등의 무기산과의 염, 초산, 푸말산, 말레산, 숙신산, 구연산, 주석산, 아디프산, 글루콘산, 글루코헵톤산, 글루쿠론산, 테레프탈산, 메탄 술폰산, 젖산, 히푸르산, 1, 2-에탄 디술폰산, 이세티온산, 락토비온산, 올레산, 파모산, 폴리갈락투론산, 스테아르산, 타닌산, 트리플루오로메탄술폰산, 벤젠 술폰산, p-톨루엔 술폰산, 황산 라우릴 에스테르, 황산메틸, 나프탈렌 술폰산, 술포 살리실산 등의 유기산과의 염, 브롬화메틸, 요오드화메틸 등과의 4급 암모늄염, 브롬 이온, 염소 이온, 요오드 이온 등의 할로겐 이온과의 염, 리튬, 나트륨, 칼륨 등의 알칼리 금속과의 염, 칼슘, 마그네슘 등의 알칼리토류 금속과의 염, 철, 아연 등과의 금속염, 암모니아와의 염, 트리에틸렌디아민, 2-아미노에탄올, 2, 2-이미노비스(에탄올), 1-데옥시-1-(메틸아미노)-2-D-소르비톨, 2-아미노-2-(하이드록시메틸)-1,3-프로판디올, 프로카인, N,N-비스(페닐메틸)-1,2-에탄디아민 등의 유기 아민과의 염 등을 들 수 있다.
본 화합물에 기하 이성체 또는 광학 이성체가 존재하는 경우에는, 이들 이성체도 본 발명의 범위에 포함된다. 또한, 본 화합물은 수화물 또는 용매화물의 형태를 취해도 된다.
본 화합물에 플로톤 호변이성이 존재하는 경우에는, 이들 호변이성체도 본 발명에 포함된다.
본 화합물에 결정 다형 및 결정 다형군(결정 다형 시스템)이 존재하는 경우에는, 이들 결정 다형체 및 결정 다형군(결정 다형 시스템)도 본 발명에 포함된다. 여기서, 결정 다형군(결정 다형 시스템)이란, 이들 결정의 제조, 결정화, 보존 등의 조건 및 상태(그리고, 본 상태는 제재화된 상태도 포함함)에 의해, 결정형이 변하는 경우의 각 단계에 있어서 각각의 결정형 및 그 과정 전체를 의미한다.
(A) 본 화합물의 예로서, 일반식 (1)로 나타내는 화합물 또는 그 염에 있어서, 각 기가 이하에 나타낸 기인 화합물 또는 그 염을 들 수 있다.
(A1) R1은 하기 일반식 (2a), (3a), (4a) 또는 (5a)를 나타내고/나타내거나;
(A2) R2는 -(CO)-R8, -(CO)O-R9, -(SO)-R10, -(SO2)-R11 또는 -(CO)NR12R13을 나타내고/나타내거나;
(A3) R2-O-는, 벤젠환 A의 4 또는 5번 위치에서 치환되고/치환되거나;
(A4) R3는 저급 알킬기를 나타내고/나타내거나;
(A5) R4, R5, R6 또는 R7은, 할로겐 원자, 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 알키닐기, 저급 알콕시기, 니트로기 또는 포르밀기를 나타내고/나타내거나;
(A6) m, n, p 또는 q는, 0, 1 또는 2를 나타내고/나타내거나;
(A7) m, n, p 또는 q가 2를 나타내는 경우, 각 R4, R5, R6 또는 R7은 동일 또는 상이해도 되고/되거나;
(A8) R8, R9, R10 또는 R11은, 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 시클로알킬기, 치환기를 가질 수 있는 아릴기 또는 치환기를 가질 수 있는 복소환기를 나타내고/나타내거나;
(A9) R12 및 R13은 동일 또는 상이해도 되며, 수소 원자, 치환기를 가질 수 있는 저급 알킬기, 치환기를 가질 수 있는 아릴기 또는 복소환기를 나타낸다.
즉, 일반식 (1)로 나타내는 화합물 또는 그 염에 있어서, 상기 (A1), (A2), (A3), (A4), (A5), (A6), (A7), (A8) 및 (A9)으로부터 선택되는 1 또는 2 이상의 각각의 조합으로 이루어지는 화합물 또는 그 염.
(B) 본 화합물의 바람직한 예로서, 일반식 (1)로 나타내는 화합물 또는 그 염에 있어서, 각 기가 이하에 나타내는 기인 화합물 또는 그 염을 들 수 있다.
(B1) R1이 하기 일반식 (2a), (3a), (4a) 또는 (5a)를 나타내고/나타내거나;
(B2) R2가 -(CO)-R8, -(CO)O-R9, -(SO)-R10, -(SO2)-R11 또는 -(CO)NR12R13을 나타내고/나타내거나;
(B3) R2-O-가, 벤젠환 A의 4 또는 5번 위치에서 치환되고/치환되거나;
(B4) R3가 저급 알킬기를 나타내고/나타내거나;
(B5) R4가 할로겐 원자, 저급 알킬기, 저급 알콕시기 또는 니트로기를 나타내고/나타내거나;
(B6) R5가 할로겐 원자, 저급 알킬기 또는 저급 알콕시기를 나타내고/나타내거나;
(B7) R6가 할로겐 원자, 저급 알킬기 또는 저급 알콕시기를 나타내고/나타내거나;
(B8) R7가 할로겐 원자 또는 저급 알킬기를 나타내고/나타내거나;
(B9) m, n 또는 p가 1 또는 2를 나타내고/나타내거나;
(B10) m, n 또는 p가 2를 나타낸 경우, 각 R4, R5 또는 R6는 동일 또는 상이해도 되고/되거나;
(B11) q가 1을 나타내고/나타내거나;
(B12) R8이 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 시클로알킬기, 치환기를 가질 수 있는 아릴기 또는 치환기를 가질 수 있는 복소환기를 나타내고/나타내거나;
(B13) R9이 치환기를 가질 수 있는 저급 알킬기 또는 치환기를 가질 수 있는 아릴기를 나타내고/나타내거나;
(B14) R10 또는 R11이, 치환기를 가질 수 있는 저급 알킬기 또는 저급 시클로알킬기를 나타내고/나타내거나;
(B15) R12 및 R13이 동일 또는 상이해도 되며, 수소 원자, 치환기를 가질 수 있는 저급 알킬기, 치환기를 가질 수 있는 아릴기 또는 복소환기를 나타낸다.
즉, 일반식 (1)로 나타내는 화합물 또는 그 염에 있어서, 상기 (B1), (B2), (B3), (B4), (B5), (B6), (B7), (B8), (B9), (B10), (B11), (B12), (B13), (B14) 및 (B15)으로부터 선택되는 1 또는 2 이상의 각각의 조합으로 이루어지는 화합물 또는 그 염.
(C) 본 화합물에 있어서의 R1의 바람직한 예로서, 일반식 (1)에 있어서, R1이 하기 일반식 (2a-1), (2a-2), (2a-3), (3a-1), (3a-2), (4a-1), (4a-2), (4a-3), (5a-1) 또는 (5a-2)를 나타내는 경우를 들 수 있다.
더욱 바람직하게는, R1이 하기 일반식 (2a-1), (2a-2), (2a-3), (3a-1), (3a-2), (4a-1), (4a-2) 또는 (5a-1)을 나타내는 경우를 들 수 있다.
또한 상기 조건 (C)과 상기 (A) 및/또는 (B)의 조건을 충족하는 화합물 또는 그 염이 특히 바람직하다.
(D) 본 화합물에 있어서의 R2의 바람직한 예로서, 일반식 (1)에 있어서, R2가 -(CO)-R8, -(SO2)-R11 또는 -(CO)NR12R13을 나타낸 경우를 들 수 있으며, 더욱 바람직하게는, R2가 -(CO)-R8 또는 -(SO2)-R11를 나타낸 경우를 들 수 있으며, 더욱 바람직하게는 R2가 -(CO)-R8을 나타낸 경우를 들 수 있다.
또한 상기 조건 (D)와 상기 (A) 및/또는 (B)의 조건을 충족하는 화합물 또는 그 염이 특히 바람직하다.
(E) 본 화합물에 있어서의 R3의 바람직한 예로서, 일반식 (1)에 있어서, R3가 메틸기를 나타낸 경우를 들 수 있다.
또한 상기 조건 (E)과 상기 (A) 및/또는 (B)의 조건을 충족하는 화합물 또는 그 염이 특히 바람직하다.
(F) 본 화합물에 있어서의 R2-O-의 바람직한 치환 위치로서, 일반식 (1)에 있어서, R2-O-가 벤젠환 A의 4번 위치에 치환된 경우를 들 수 있다.
또한 상기 조건 (F)과 상기 (A) 및/또는 (B)의 조건을 충족하는 화합물 또는 그 염이 특히 바람직하다.
(G) 본 화합물의 바람직한 구체예로서, 이하의 화합물 또는 그 염을 들 수 있다.
·6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-부틸릴옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소부틸릴옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-페닐아세톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[5-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-5-프로피오닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-아세톡시벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(5-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-t-부틸카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로피리딘-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(3-플루오르피리딘-4-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시-5-니트로페녹시메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-벤조일옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(4-메틸벤조일옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-벤조일옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(4-메톡시벤조일옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-이소프로필카르보닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-아세톡시벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-니트로벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소프로필설포닐옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-부틸설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(2-메톡시-4-메틸설포닐옥시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3,3,3-트리플루오르프로필설포닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로펜틸술포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-[N-(2-디메틸아미노에틸)-N-에틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-클로로페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
본 화합물은, 이하의 방법에 의해 제조할 수 있다. 그리고, 각각의 구체적인 제조 방법에 대해서는, 후술하는 실시예 「제조예」 부분에서 상세하게 설명한다. 또한, 이들의 예시는 본 발명을 더욱 잘 이해하기 위한 것이며, 본 발명의 범위를 한정하는 것은 아니다. 그리고, 하기의 합성 경로에 나타나는 hal은 할로겐 원자, Fmoc는 9-플루오레닐메톡시카르보닐기를 의미한다.
본 화합물 (I)-(a)(일반식 (1)에 있어서 R2가 -(CO)-R8인 화합물), 본 화합물 (I)-(b)(일반식 (1)에 있어서 R2가 -(CO)O-R9인 화합물), 본 화합물 (I)-(c)(일반식 (1)에 있어서 R2가 -(SO2)-R11인 화합물), 본 화합물 (I)-(d)(일반식 (1)에 있어서 R2가 -(CO)NR12R13인 화합물)는 합성 경로 1에 따라 합성할 수 있다. 즉, 화합물 (II)을 염화메틸렌, 피리딘, 테트라하이드로퓨란(이하, 「THF」라고 함), N,N-디메틸포름아미드(이하, 「DMF」라고 함) 등의 유기용매 중에서, 트리에틸아민, 디이소프로필 에틸아민(이하, 「DIEA」라고 함) 등의 염기 존재 하에서, 대응하는 산 할로겐화물 (III), (IV), (V), (VI)와 0℃ 내지 100℃로, 10분 내지 2일간 반응시킴으로써 본 화합물 (I)-(a), (I)-(b), (I)-(c), (I)-(d)를 얻을 수 있다.
합성 경로 1
또한 본 화합물 (I)-(a)(일반식 (1)에 있어서 R2가 -(CO)-R8인 화합물)는 합성 경로 2에 따라 합성할 수도 있다. 즉, 화합물 (II)을 염화메틸렌, DMF 등의 유기용매 중에서, 트리에틸아민, DIEA 등의 염기, N, N'-디시클로헥실카르보디이미드, O-(7-아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄 헥사플루오로포스페이트 등의 축합제 존재 하, 대응하는 카르복실산(VII)과 0℃ 내지 실온에서, 30분 내지 3일간 반응시킴으로써 본 화합물 (I)-(a)를 얻을 수 있다.
합성 경로 2
본 화합물 (I)-(d)(일반식 (1)에 있어서 R2가 -(CO)NR12R13인 화합물)는 합성 경로 3에 따라 합성할 수도 있다. 즉, 화합물 (II)과 1, 1'-카르보닐디이미다졸(이하, 「CDI」라고 함)을 디클로로메탄, THF 등의 유기용매 중에서, 4-디메틸아미노 피리딘 등의 촉매 존재 하, 실온 내지 50℃로, 30분 내지 12시간 반응시킨 후, 대응하는 아민(VIII)과 실온 내지 100℃로, 30분 내지 5시간 반응시킴으로써, 본 화합물 (I)-(d)를 얻을 수 있다.
합성 경로 3
본 화합물 (I)-(e)(일반식 (1)에 있어서 R2가 -(CO)NR12R13, R13이 수소 원자인 화합물)는 합성 경로 4에 따라 합성할 수 있다. 즉, 화합물 (II)을 디클로로메탄, THF, DMF 등의 유기용매 중에서, 트리에틸아민, DIEA 등의 염기 존재 하, 대응하는 이소시아네이트(IX)와 0℃ 내지 실온에서, 30분 내지 1일간 반응시킴으로써 본 화합물 (I)-(e)를 얻을 수 있다.
합성 경로 4
본 화합물 (I)-(f)(일반식 (1)에 있어서 R1이 (3a)기인 화합물)는 합성 경로 5에 따라 합성할 수도 있다. 즉, 합성 경로 1∼4의 방법에 따라 화합물 (X)에 R2를 도입한 후, DMF, 디클로로메탄 등의 유기용매 중에서, 피페리딘 등의 염기 존재 하, 0℃ 내지 50℃로, 5분 내지 24시간 처리함으로써, 본 화합물 (I)-(f)를 얻을 수 있다.
합성 경로 5
화합물 (II)-(a)(화합물 (II)에 있어서 R1이 (2a)기인 화합물), 화합물 (II)-(b)(화합물 (II)에 있어서 R1이 (3a)기인 화합물), 화합물 (II)-(c)(화합물 (II)에 있어서 R1이 (4a)기인 화합물), 화합물 (II)-(d)(화합물 (II)에 있어서 R1이 (5a)기인 화합물)는 합성 경로 6에 따라 합성할 수 있다. 즉, 화합물 (XI)과 염화 메탄술포닐을 염화메틸렌, DMF 등의 유기용매 중에서, 트리에틸아민, DIEA 등의 염기 존재 하, 0℃ 내지 실온에서, 30분 내지 3일간 반응시킴으로써 화합물 (XII)을 얻을 수 있다. 얻어진 화합물 (XII)에 대응하는 페놀류(XIII), 아닐린류(XIV), 벤조산류(XV) 또는 티오펜카르복실산류(XVI)를 DMF, 염화메틸렌 등의 유기용매 중에서, 탄산칼륨, DIEA, 수소화 나트륨 등의 염기 존재 하, 50℃ 내지 100℃로 1시간 내지 2일간 반응시킴으로써 화합물 (XVII)-(a)~(XVII)-(d)를 얻을 수 있다. 얻어진 화합물 (XVII)-(a)~(XVII)-(d)를 염화메틸렌이나 1,4-디옥산 등의 유기용매 중에서, 염화수소나 트리플루오로아세트산 등의 산으로 0℃ 내지 실온에서 1시간 내지 2일간 처리함으로써 화합물 (II)-(a)~(II)-(d)를 얻을 수 있다.
합성 경로 6
화합물 (II)-(a)(화합물 (II)에 있어서 R1이 (2a)기인 화합물), 화합물 (II)-(c)(화합물 (II)에 있어서 R1이 (4a)기인 화합물), 화합물 (II)-(d)(화합물 (II)에 있어서 R1이 (5a)기인 화합물)는 합성 경로 7에 따라 합성할 수도 있다. 즉, 화합물 (XI)에 대응되는 페놀류(XIII), 벤조산류(XV) 또는 티오펜카르복실산류(XVI)를 벤젠, THF 등의 유기용매 중에서, 트리페닐포스핀, 트리부틸포스핀 등의 포스핀과 디에틸아조디카르복실레이트, 디이소프로필아조디카르복실레이트, 1, 1'-(아조디카르보닐)디피페리딘 등의 시약 존재 하, 실온에서 1시간 내지 2일간 반응시킴으로써 화합물 (XVII)-(a), (XVII)-(c), (XVII)-(d)를 얻을 수 있다. 얻어진 화합물 (XVII)-(a), (XVII)-(c), (XVII)-(d)를 염화메틸렌이나 1, 4-디옥산 등의 유기용매 중에서, 염화수소나 트리플루오로아세트산 등의 산으로 0℃ 내지 실온에서 1시간 내지 2일간 처리하는 것에 의해 화합물 (II)-(a), (II)-(c), (II)-(d)를 얻을 수 있다.
합성 경로 7
화합물 (X)은 합성 경로 8에 따라 합성할 수 있다. 즉, (II)-(b)와 염화 9-플루오레닐메톡시카르보닐을 1, 4-디옥산, 물 등의 용매 중에서, 탄산수소나트륨 등의 염기 존재 하, 0℃ 내지 50℃로, 1시간 내지 24시간 반응시킴으로써, 화합물 (X)을 얻을 수 있다.
합성 경로 8
화합물 (XI)은 합성 경로 9에 따라 합성할 수 있다. 즉 붕소산(XVIII)과 할로겐 화합물이나 트리플레이트 화합물 (XIX)을 DMF, 에탄올, 톨루엔, 물 등의 용매 중에서, 탄산 세슘, 탄산나트륨이나 인산 칼륨 등의 염기와 이염화 비스(트리페닐포스핀)팔라듐(II)이나 테트라키스(트리페닐포스핀)팔라듐(0) 등의 촉매 존재 하, 50℃ 내지 120℃로, 12시간 내지 2일간 반응시킴으로써 화합물 (XX)을 얻을 수 있다. 얻어진 화합물 (XX)을 염화메틸렌, THF 등의 용매 중에서, 삼브롬화붕소나 염산 등의 산 존재 하, -78℃ 내지 실온에서, 1시간 내지 1일간 처리하는 것에 의해 화합물 (XXI)을 얻을 수 있다. 얻어진 화합물 (XXI)을 메탄올, 에탄올, 1, 4-디옥산, THF 등의 유기용매 중에서, 수소 분위기 아래, 팔라듐 탄소, 이산화 백금 등의 촉매 존재 하, 실온에서 2시간 내지 2일간 처리하는 것에 의해 화합물 (XXII)을 얻을 수 있다. 얻어진 화합물 (XXII)을 아세톤 중에서, 요오드 존재 하, 80℃ 내지 130℃로, 24시간 내지 5일간 처리하는 것에 의해 화합물 (XXIII)을 얻을 수 있다. 얻어진 화합물 (XXIII)과 클로로디메틸에테르를 염화메틸렌, DMF 등의 유기용매 중에서, 탄산칼륨, 트리에틸아민, 디이소프로필에틸아민 등의 아민 존재 하, 반응시킴으로써 화합물 (XXIV)을 얻을 수 있다. 얻어진 화합물 (XXIV)을 디에틸에테르, THF 등의 유기용매 중에서, 수소화 리튬 알루미늄 등의 환원제의 존재 하, 0℃ 내지 50℃로, 1시간 내지 1일간 처리함으로써, 화합물 (XXV)을 얻을 수 있다. 얻어진 화합물 (XXV)에 대응되는 할로겐화 화합물 (XXVI)을 DMF, 에탄올 등의 유기용매 중에서, 탄산칼륨, DIEA 등의 염기 존재 하, 실온 내지 100℃로, 1시간 내지 24시간 반응시킴으로써 화합물 (XI)을 얻을 수 있다.
합성 경로 9
이와 관련하여 상세한 것은 후술하는 실시예 「약리 시험」 부분에서 상세하게 설명하지만, 먼저, 글루코코르티코이드 수용체(이하, 「GR」라고 함) 경쟁 어세이 키트(인비트로젠사 제품, Cat No.P2816)를 사용하여, 편광 형광법으로 수용체 경쟁 어세이를 수행하고, 본 화합물의 GR에 대한 결합 활성에 대하여 검토했다. 그 결과, 본 화합물은, GR에 대하여, 64% 이상의 GR 결합율을 나타내었다.
다음에, 본 화합물의 GR 작용제로서의 효과를 평가하기 위해, 리포폴리사카라이드(이하, 「LPS」라고 함) 자극 후의 사람의 각막상피세포주에 있어서의 IL-6 생성 억제 작용을 검토했다. 그 결과, 본 화합물은 우수한 IL-6 생성 억제 작용을 나타낸다. 즉, 본 화합물은 GR 작용제 활성을 가지고, 염증성 질환의 예방 또는 치료제로서 유용하다.
또한, 본 화합물의 점안 투여에 의한 전안부 염증치료제로서의 가능성을 평가하기 위해, 마우스 알레르기성 결막염 모델에 대한 본 화합물의 색소 누출량 억제 효과 및 래트 각막 장해 모델에 대한 본 화합물의 각막 장해의 개선 효과를 검토했다. 그 결과, 본 화합물은 혈관 투과성 항진 억제 작용 및 각막 장해의 개선 효과를 나타낸다. 즉, 본 화합물은 전안부 염증성 질환의 예방 또는 치료제, 특히 알레르기성 결막염 및 안구 건조 증후군(「건성안」이라고도 함)의 예방 또는 치료제로서 유용하다.
또한, 본 화합물의 후안부 염증성 질환의 예방 또는 치료제로서의 가능성을 평가하기 위해, 래트 맥락막 혈관 신생 모델에 본 화합물을 점안 투여하여 맥락막 혈관 신생 저해 효과를 검토했다. 그 결과, 본 화합물은 신생 혈관 억제 작용을 나타낸다. 즉, 본 화합물은 후안부 염증성 질환의 예방 또는 치료제, 특히 연령관련 황반변성이나 당뇨성 망막증 등의 망막질환의 예방 또는 치료제로서 유용하다.
또한, 본 화합물의 피부염의 예방 또는 치료제로서의 가능성을 평가하기 위해, 마우스 아토피성 피부염 모델에 본 화합물을 도포 투여하여 혈관 투과성 항진 억제 효과를 검토했다. 그 결과, 본 화합물은 본 모델에 있어서도, 혈관 투과성 항진 억제 작용을 나타낸다. 즉, 본 화합물은 피부염의 예방 또는 치료제, 특히 아토피성 피부염의 예방 또는 치료제로서 유용하다.
이상의 약리 시험에 의해, 본 화합물은, GR 작용제, 상기 GR 작용제 중 적어도 하나를 유효 성분으로서 함유하는 의약 조성물, 상기 GR 작용제 중 적어도 하나를 유효 성분으로서 함유하는 염증성 질환 또는 면역 질환의 예방 또는 치료제, 상기 GR 작용제 중 적어도 하나를 유효 성분으로서 함유하는 안염증성 질환 또는 피부염의 예방 또는 치료제 등으로서 유용하다.
본 화합물은 경구 또는 비경구로 투여할 수 있다. 투여제형으로서, 정제, 캡슐제, 과립제, 산제, 주사제, 점안제, 좌제, 경피흡수제제, 연고제, 에어졸제(흡입제 포함함) 등을 들 수 있고, 이들은 범용되는 기술을 이용하여 제제화할 수 있다.
예를 들면, 정제, 캡슐제, 과립제, 산제 등의 경구제는, 유당, 만니톨, 전분, 결정 셀룰로오스, 경질 무수 규산, 탄산칼슘, 인산 수소 칼슘 등의 부형제, 스테아르산, 스테아르산 마그네슘, 탈크 등의 활택제, 전분, 하이드록시프로필 셀룰로오스, 하이드록시프로필메틸 셀룰로오스, 폴리비닐 피롤리돈 등의 결합제, 카르복시메틸 셀룰로오스, 저치환도 하이드록시프로필메틸 셀룰로오스, 구연산 칼슘 등의 붕해제, 하이드록시프로필메틸 셀룰로오스, 마크로콜, 실리콘 수지 등의 코팅제, 파라옥시 벤조산 에틸, 벤질 알코올 등의 안정화제, 감미료, 산미료, 향료 등의 교미교취제 등을 필요에 따라 필요량을 사용하여 조제할 수 있다.
또한, 주사제, 점안제 등의 비경구제는, 염화 나트륨, 농글리세린, 프로필렌글리콜, 폴리에틸렌 글리콜, 염화 칼륨, 소르비톨, 만니톨 등의 등장화제, 인산 나트륨, 인산 수소 나트륨, 초산나트륨, 구연산, 빙초산, 트로메타몰 등의 완충화제, 폴리소르베이트 80, 스테아르산 폴리옥시 40, 폴리옥시에틸렌 경화 피마자유 60 등의 계면활성제, 구연산 나트륨, 에데트산 나트륨 등의 안정화제, 염화 벤잘코늄, 파라벤, 염화 벤조토늄, 파라옥시벤조산 에스테르, 벤조산 나트륨, 클로로부탄올, 소르빈산 등의 방부제, 염산, 구연산, 인산, 빙초산, 수산화나트륨, 탄산나트륨, 탄산수소나트륨 등의 pH 조정제, 벤질 알코올 등의 무통화제 등을 필요에 따라 필요량을 사용하여 조제할 수 있다.
본 화합물의 투여량은, 증상, 연령, 제형 등에 따라 적절하게 선택하여 사용할 수 있다. 예를 들면, 경구제는 통상 1일 0.01~1000 mg, 바람직하게는 1~100 mg를 1회 또는 수회로 나누어 투여할 수 있다. 또한, 점안제는 통상 0.0001%~10%(w/v), 바람직하게는 0.01%∼5%(w/v)의 농도로 1회 또는 수회로 나누어 투여할 수 있다.
본 발명은 의약으로서 유용한, 본 화합물로 이루어지는 글루코코르티코이드 수용체 작용제, 상기 글루코코르티코이드 수용체 작용제 중 적어도 하나를 유효 성분으로서 함유하는 의약 조성물, 상기 글루코코르티코이드 수용체 작용제 중 적어도 하나를 유효 성분으로서 함유하는 염증성 질환의 예방 또는 치료제 및 상기 글루코코르티코이드 수용체 작용제 중 적어도 하나를 유효 성분으로서 함유하는 안염증성 질환 또는 피부염의 예방 또는 치료제를 제공한다.
특히 본 발명의 글루코코르티코이드 수용체 작용제는 안염증성 질환 또는 피부염의 예방 또는 치료제로서 유용하고, 각막염, 각결막염, 결막염, 안검염, 안구 건조 증후군(「건성안」이라고도 함), 알레르기성 결막염, 앞부분 포도막염, 전안부의 수술 후 염증, 눈 조직 이식 거부반응에 의한 염증 등의 전안부 염증성 질환, 연령관련 황반변성, 당뇨성 망막증, 당뇨성 황반부종, 혈관신생 황반증, 돌발성 황반상막, 증식성 유리체 망막증, 망막색소 변성증, 망막 중심 정맥 폐색증, 망막 중심 동맥 폐색증, 망막정맥 분지 폐색증, 망막동맥 분지 폐색증, 망막박리나 외상에 의한 염증이나 변성, 후안부의 수술 후 염증, 망막염, 포도막염, 공막염, 시신경염 등의 후안부 염증성 질환 및/또는 습진·피부염군, 양진군, 두드러기, 건선 및 유사건선, 아토피성 피부염 등의 피부염의 예방 또는 치료제로서 유용하다.
이하 본 화합물의 제조예, 제제예 및 약리 시험의 결과를 나타낸다. 이러한 예시는 본 발명을 더욱 잘 이해하기 위한 것이며, 본 발명의 범위를 한정하는 것은 아니다.
[제조예]
참고예 1
5-하이드록시메틸-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-1)
2-(2,4-디메톡시페닐)-5-니트로벤조산메틸(참고 화합물 1-1-(1))
2,4-디메톡시페닐 붕소산(25.0 g, 137 mmol), 2-브로모-5-니트로벤조산메틸(35.7 g, 137 mmol), 탄산 세슘(89.4 g, 274 mmol) 및 이염화 비스(트리페닐포스핀)팔라듐(II)(4.81 g, 6.85 mmol)의 혼합물을 N,N-디메틸포름아미드(450 mL)에 현탁하고, 아르곤 질소 분위기 아래, 80℃에서 밤새 교반했다. 냉각 후, 에틸아세테이트(200 mL), 디에틸에테르(400 mL) 및 물 (1000 mL)을 가하여 분배했다. 수층을 에틸아세테이트(150 mL)-디에틸에테르(150 mL)의 혼합 용매로 추출(2회)했다. 유기층을 모아서, 물 (500 mL, 3회) 및 포화 식염수(500 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 증류 제거함으로써 표기 참고 화합물을 갈색 오일상으로서 얻었다. (정량적)
1 H-NMR (400 MHz, CDCl3) δ 3.71 (s, 3 H), 3.76 (s, 3 H), 3.87 (s, 3 H), 6.49 (d, J = 2.3 Hz, 1 H), 6.60 (dd, J = 8.3, 2.3 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.49 (d, J = 8.5 Hz, 1 H), 8.35 (dd, J = 8.5, 2.5 Hz, 1 H), 8.67 (d, J = 2.5 Hz, 1 H) |
3-하이드록시-8-니트로벤조[c]크로멘-6-온(참고 화합물 1-1-(2))
2-(2,4-디메톡시페닐)-5-니트로벤조산메틸(참고 화합물 1-1-(1), 43.5 g, 137 mmol)의 무수 염화메틸렌(250 mL) 용액을 -78℃로 냉각시키고, 삼브롬화붕소(96.2 g, 384 mmol)를 적하 후, 실온에서 1시간 교반했다. -50℃로 냉각시키고, 메탄올(300 mL)을 가하였다. 석출물을 메탄올로 여과하여 표기 참고 화합물 (18.0 g)를 황색 고체로서 얻었다. (수율 51%)
1 H-NMR (400 MHz, DMSO-d6) δ 6.81 (d, J = 2.4 Hz, 1 H), 6.91 (dd, J = 8.8, 2.4 Hz, 1 H), 8.28 (d, J = 8.8 Hz, 1 H), 8.50 (d, J = 8.9 Hz, 1 H), 8.60 (dd, J = 8.9, 2.4 Hz, 1 H), 8.82 (d, J = 2.4 Hz, 1 H), 10.75 (s, 1 H) |
8-아미노-3-하이드록시벤조[c]크로멘-6-온(참고 화합물 1-1-(3))
3-하이드록시-8-니트로벤조[c]크로멘-6-온(참고 화합물 1-1-(2), 52.01 g, 202 mmol)를 메탄올(150 mL)-N,N-디메틸포름아미드(600 mL)에 용해하고, 10% 팔라듐-탄소(5.00 g)를 가하여, 가압(3 kgf/cm2) 수소 분위기 아래, 실온에서 밤새 교반했다. 불용물을 여과한 후, 감압하 메탄올을 제거했다. 잔류물에 물 (2 L)을 가하였다. 석출한 고체를 여과하고, 감압하 90℃에서 건조함으로써 표기 참고 화합물 (44.02 g)를 담황색 고체로서 얻었다. (수율 96%)
1 H-NMR (400 MHz, DMSO-d6) δ 6.02 (s, 2 H), 7.17 (dd, J = 8.5, 2.4 Hz, 1 H), 7.37-7.41 (m, 1 H), 7.37 (d, J = 2.4 Hz, 1 H), 7.96 (ddd, J = 9.3, 5.4, 2.2 Hz, 1 H), 8.08 (d, J = 8.5, Hz, 1 H) |
8-하이드록시-2,2,4-트리메틸-1,2-디하이드로-6-옥사-1-아자크리센-5-온(참고 화합물 1-1-(4))
내압관 중에서, 8-아미노-3-하이드록시벤조[c]크로멘-6-온(참고 화합물 1-1-(3), 40.0 g, 176 mmol)를 아세톤(440 mL)-N-메틸 피롤리돈(240 mL)에 용해하고, 요오드(17.9 g, 70.5 mmol)를 가하여 밀봉한 후, 110℃으로 3일간 교반했다. 냉각 후, 감압하 아세톤을 제거했다. 얻어진 잔류물에 에틸아세테이트(700 mL), 헥산(150 mL) 및 1% 티오황산나트륨 수용액(700 mL)을 가하여 분배했다. 수층을 에틸아세테이트(250 mL)-헥산(50 mL)의 혼합 용매로 추출(3회)했다. 유기층을 모아서, 물 (500 mL, 3회) 및 포화 식염수(500 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물에 클로로포름(150 mL)을 가하여 불용물을 제거했다. 여액을 농축한 후, 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 참고 화합물 (26.0 g)를 황색 고체로서 얻었다. (수율 48%)
1 H-NMR (500 MHz, DMSO-d6) δ 1.23 (s, 6 H), 1.97 (s, 3 H), 5.48 (s, 1 H), 7.05 (s, 1 H), 7.19 (d, J = 8.9 Hz, 1 H), 7.37 (td, J = 9.7, 7.6 Hz, 1 H), 7.95 (ddd, J = 9.7, 5.2, 1.8 Hz, 1 H), 7.98 (d, J = 8.9, Hz, 1 H) |
8-메톡시메톡시-2,2,4-트리메틸-1,2-디하이드로-6-옥사-1-아자크리센-5-온(참고 화합물 1-1-(5))
8-하이드록시-2,2,4-트리메틸-1,2-디하이드로-6-옥사-1-아자크리센-5-온(참고 화합물 1-1-(4), 1.00 g, 3.25 mmol), 클로로 디메틸에테르(420㎕, 5.53 mmol) 및 탄산칼륨(1.35 g, 9.77 mmol)의 혼합물을 무수 N,N-디메틸포름아미드(15 mL)에 현탁하고, 50℃에서 밤새 교반했다. 냉각 후, 에틸아세테이트(100 mL) 및 디에틸에테르(100 mL)를 가하였다. 물 (150 mL, 100 mL) 및 포화 식염수(100 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 참고 화합물 (747 mg)을 황색 고체로서 얻었다. (수율 66%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.22 (s, 6 H), 1.95 (s, 3 H), 3.40 (s, 3 H), 5.27 (s, 2 H), 5.43 (s, 1 H), 6.85 (s, 1 H), 6.98 (d, J = 9.3 Hz, 1 H), 6.99 (s, 1 H), 7.16 (d, J = 8.8 Hz, 1 H), 7.92 (d, J = 8.8 Hz, 1 H), 8.04 (d, J = 9.3 Hz, 1 H) |
6-(2-하이드록시-4-메톡시메톡시페닐)-5-하이드록시메틸-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-1-(6))
수소화 리튬 알루미늄(167 mg, 4.40 mmol)를 무수 테트라하이드로퓨란(3 mL)에 현탁했다. 0℃으로 8-메톡시메톡시-2,2,4-트리메틸-1,2-디하이드로-6-옥사-1-아자크리센-5-온(참고 화합물 1-1-(5), 744.1 mg, 2.12 mmol)의 무수 테트라하이드로퓨란(10 mL) 용액을 적하하고, 동온에서 30분간 교반했다. 반응액에 에틸아세테이트(2 mL) 및 물 (1 mL)을 순차적으로 적하한 후, 에틸아세테이트(150 mL)를 가하였다. 1N 염산 수용액(6 mL)을 부가한 후, 물 (100 mL, 2회) 및 포화 식염수(50 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조했다. 감압하 용매를 증류 제거함으로써 표기 참고 화합물 (750.6 mg)를 담황색 아몰퍼스로서 얻었다. (정량적)
1 H-NMR (500 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.20 (s, 3 H), 2.23 (s, 3 H), 3.39 (s, 3 H), 4.26 (dd, J = 11.0, 6.6 Hz, 1 H), 4.33 (t, J = 6.6 Hz, 1 H), 4.44 (dd, J = 11.0, 6.6 Hz, 1 H), 5.14 (s, 2 H), 5.33 (s, 1 H), 5.76 (s, 1 H), 6.49 (dd, J = 8.4, 2.6 Hz, 1 H), 6.53 (d, J = 8.3 Hz, 1 H), 6.56 (d, J = 2.6 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 9.23 (s, 1 H) |
5-하이드록시메틸-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-1)
6-(2-하이드록시-4-메톡시메톡시페닐)-5-하이드록시메틸-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-1-(6), 746.1 mg, 2.10 mmol), 요오드화메틸(131㎕, 2.10 mmol) 및 탄산칼륨(582 mg, 4.21 mmol)의 혼합물을 무수 N,N-디메틸포름아미드(10 mL)에 현탁하고, 50℃에서 1시간 교반했다. 냉각 후, 에틸아세테이트(50 mL) 및 디에틸에테르(50 mL)를 가하여 희석했다. 물 (100 mL, 2회) 및 포화 식염수(50 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 참고 화합물 (513.2 mg)를 무색 고체로서 얻었다. (수율 66%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.20 (s, 3 H), 2.23 (s, 3 H), 3.41 (s, 3 H), 3.65 (s, 3 H), 4.14 (d, J = 12.2 Hz, 1 H), 4.33 (br s, 1 H), 4.45 (d, J = 12.2 Hz, 1 H), 5.22 (s, 2 H), 5.32 (s, 1 H), 5.78 (s, 1 H), 6.51 (d, J = 8.3 Hz, 1 H), 6.61-6.64 (m, 2 H), 6.66 (d, J = 2.4 Hz, 1 H), 7.05 (d, J = 8.3 Hz, 1 H) |
이하, 시판 화합물을 사용하고, 참고 화합물 1-1의 제조 방법에 준하여, 참고 화합물 1-2를 얻었다.
5-하이드록시메틸-6-(2-메톡시-5-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-2) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.21 (s, 3 H), 2.24 (s, 3 H), 3.38 (s, 3 H), 3.62 (s, 3 H), 4.15 (dd, J = 12.2, 4.7 Hz, 1 H), 4.38 (t, J = 4.7 Hz, 1 H), 4.47 (dd, J = 12.2, 4.7 Hz, 1 H), 5.11 (d, J = 6.5 Hz, 1 H), 5.13 (d, J = 6.5 Hz, 1 H), 5.33 (s, 1 H), 5.84 (s, 1 H), 6.53 (d, J = 8.2 Hz, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.85 (d, J = 2.6 Hz, 1 H), 6.90-6.96 (m, 2 H) |
참고예 2
5-클로로메틸-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 2)
5-하이드록시메틸-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-1, 1.02 g, 2.76 mmol)를 무수 디클로로메탄(10 mL)에 용해하고, 트리에틸아민(0.490 mL, 3.52 mmol) 및 염화 메탄술포닐(231㎕, 2.98 mmol)를 순차적으로 가하였다. 반응액을 실온에서 5시간 교반했다. 반응액에 클로로포름(50 mL) 및 물 (50 mL)을 가하여 분배했다. 유기층을 포화 식염수(50 mL)로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 참고 화합물 (515 mg)을 오렌지색 아몰퍼스로서 얻었다. (수율 49%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.20 (s, 3 H), 2.26 (s, 3 H), 3.42 (s, 3 H), 3.67 (s, 3 H), 4.40 (d, J = 11.7 Hz, 1 H), 4.80 (d, J = 11.7 Hz, 1 H), 5.23 (s, 2 H), 5.45 (s, 1 H), 6.01 (br s, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.66 (dd, J = 8.3, 2.4 Hz, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.70 (d, J = 2.4 Hz, 1 H), 7.03 (d, J = 8.3 Hz, 1 H) |
참고예 3
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-1)
5-하이드록시메틸-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 1-1, 511.7 mg, 1.39 mmol), 5-플루오르-2-메틸 페놀(182㎕, 1.67 mmol), 트리-n-부틸포스핀(521㎕, 2.09 mmol), 1, 1'-(아조디카르보닐)디피페리딘(526 mg, 2.08 mmol)를 무수 벤젠(8 mL)에 용해하고, 아르곤 분위기 아래, 실온에서 1시간 교반했다. 반응액에 헥산(15 mL)을 부가하여, 불용물을 여과했다. 액을 감압 농축하고, 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (411.4 mg)를 무색 아몰퍼스로서 얻었다. (수율 62%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.20 (s, 3 H), 2.23 (s, 3 H), 3.41 (s, 3 H), 3.65 (s, 3 H), 4.14 (d, J = 12.2 Hz, 1 H), 4.33 (br s, 1 H), 4.45 (d, J = 12.2 Hz, 1 H), 5.22 (s, 2 H), 5.32 (s, 1 H), 5.78 (s, 1 H), 6.51 (d, J = 8.3 Hz, 1 H), 6.61-6.64 (m, 2 H), 6.66 (d, J = 2.4 Hz, 1 H), 7.05 (d, J = 8.3 Hz, 1 H) |
이하, 참고 화합물 1-1 또는 1-2를 사용하고, 참고 화합물 3-1의 제조 방법에 준하여, 참고 화합물 3-2∼3-9를 얻었다.
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-5-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-2) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.29 (s, 3 H), 3.67 (s, 3 H), 4.62 (d, J = 12.1 Hz, 1 H), 5.02 (d, J = 6.7 Hz, 1 H), 5.06 (d, J = 6.7 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.35 (dd, J = 11.6, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.86 (d, J = 2.7 Hz, 1 H), 6.95 (dd, J = 8.9, 2.7 Hz, 1 H), 6.97 (d, J = 8.9 Hz, 1 H), 7.02-7.05 (m, 1 H) |
6-(2-메톡시-4-메톡시메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-3) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.87 (s, 3 H), 1.17 (s, 3 H), 2.13 (s, 3 H), 2.18 (s, 3 H), 3.39 (s, 3 H), 3.72 (s, 3 H), 4.79 (d, J = 12.7 Hz, 1 H), 5.21 (s, 2 H), 5.31 (d, J = 12.7 Hz, 1 H), 5.38 (s, 1 H), 5.97 (s, 1 H), 6.59 (d, J = 8.2 Hz, 1 H), 6.65 (dd, J = 8.2, 2.4 Hz, 1 H), 6.70 (d, J = 2.4 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 7.12 (d, J = 2.1 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H), 7.32 (d, J = 8.7 Hz, 1 H), 7.62 (dd, J = 8.7, 2.1 Hz, 1 H) |
6-(2-메톡시-4-메톡시메톡시페닐)-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-4) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.01 (s, 3 H), 1.17 (s, 3 H), 2.14 (s, 3 H), 3.67 (s, 3 H), 3.82 (s, 3 H), 3.90 (s, 3 H), 4.67 (d, J = 12.1 Hz, 1 H), 5.17 (s, 2 H), 5.25 (d, J = 12.1 Hz, 1 H), 5.38 (s, 1 H), 5.96 (s, 1 H), 6.54 (dd, J = 8.4, 2.3 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.64 (d, J = 2.3 Hz, 1 H), 6.72 (d, J = 8.1 Hz, 1 H), 7.04 (d, J = 8.4 Hz, 1 H), 7.08 (d, J = 8.9 Hz, 1 H), 7.28 (d, J = 2.7 Hz, 1 H), 7.80 (dd, J = 8.9, 2.7 Hz, 1 H) |
6-(2-메톡시-4-메톡시메톡시페닐)-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-5) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.35 (s, 3 H), 3.39 (s, 3 H), 3.64 (s, 3 H), 4.97 (d, J = 12.8 Hz, 1 H), 5.20 (d, J = 12.8 Hz, 1 H), 5.20 (s, 2 H), 5.44 (s, 1 H), 6.05 (s, 1 H), 6.58 (dd, J = 8.3, 2.3 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.66 (d, J = 2.3 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 7.04 (d, J = 8.3 Hz, 1 H), 7.27 (d, J = 7.9 Hz, 2 H), 7.71 (d, J = 7.9 Hz, 2 H) |
6-(2-메톡시-4-메톡시메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-6) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.07 (s, 3 H), 2.47 (s, 3 H), 3.40 (s, 3 H), 3.64 (s, 3 H), 4.90 (d, J = 12.7 Hz, 1 H), 5.16 (d, J = 12.7 Hz, 1 H), 5.21 (s, 2 H), 5.43 (s, 1 H), 6.04 (s, 1 H), 6.59 (dd, J = 8.3, 2.4 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.67 (d, J = 2.4 Hz, 1 H), 6.73 (d, J = 8.3 Hz, 1 H), 6.88 (dd, J = 3.7, 1.1 Hz, 1 H), 7.02 (d, J = 8.3 Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H) |
5-(3-플루오르벤조일옥시메틸)-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-7) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 3.40 (s, 3 H), 3.65 (s, 3 H), 5.05 (d, J = 12.8 Hz, 1 H), 5.20 (s, 2 H), 5.25 (d, J = 12.8 Hz, 1 H), 5.46 (s, 1 H), 6.07 (s, 1 H), 6.59 (dd, J = 8.2, 2.4 Hz, 1 H), 6.65 (d, J = 8.1 Hz, 1 H), 6.67 (d, J = 2.4 Hz, 1 H), 6.75 (d, J = 8.1 Hz, 1 H), 7.04 (d, J = 8.2 Hz, 1 H), 7.47-7.57 (m, 3 H), 7.66 (dt, J = 7.6, 1.4 Hz, 1 H) |
5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-8) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.12 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.40 (s, 3 H), 3.65 (s, 3 H), 4.97 (d, J = 12.9 Hz, 1 H), 5.20 (d, J = 12.9 Hz, 1 H), 5.21 (s, 2 H), 5.45 (s, 1 H), 6.06 (s, 1 H), 6.59 (dd, J = 8.3, 2.3 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.67 (d, J = 2.3 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 7.03 (d, J = 8.3 Hz, 1 H), 7.33 (d, J = 4.0 Hz, 1 H), 7.49 (d, J = 4.0 Hz, 1 H) |
5-(4-메톡시벤조일옥시메틸)-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-9) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 3.40 (s, 3 H), 3.64 (s, 3 H), 3.81 (s, 3 H), 4.95 (d, J = 12.9 Hz, 1 H), 5.18 (d, J = 12.9 Hz, 1 H), 5.20 (s, 2 H), 5.44 (s, 1 H), 6.05 (br s, 1 H), 6.59 (dd, J = 8.3, 2.3 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.66 (d, J = 2.3 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 6.99 (d, J = 8.9 Hz, 2 H), 7.04 (d, J = 8.3 Hz, 1 H), 7.77 (d, J = 8.9 Hz, 2 H) |
참고예 4
6-(2-메톡시-4-메톡시메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 4-1)
5-클로로메틸-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 2, 262 mg, 0.675 mmol), 2-메톡시 아닐린(84 ㎕, 0.74 mmol) 및 탄산칼륨(151 mg, 1.09 mmol)의 혼합물을 무수 N,N-디메틸포름아미드(4 mL)에 현탁하고, 80℃으로 밤새 교반했다. 냉각 후, 에틸아세테이트(20 mL) 및 물 (20 mL)을 가하여 분배했다. 유기층을 포화 식염수(20 mL)로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 참고 화합물 (196 mg)을 황색 아몰퍼스로서 얻었다. (수율 61%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 3.37 (s, 3 H), 3.64 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.1, 3.3 Hz, 1 H), 4.03 (dd, J = 12.1, 6.5 Hz, 1 H), 4.23 (dd, J = 6.5, 3.3 Hz, 1 H), 5.17 (s, 2 H), 5.38 (s, 1 H), 5.95 (s, 1 H), 6.36 (dd, J = 7.8, 1.4 Hz, 1 H), 6.50 (td, J = 7.8, 1.4 Hz, 1 H), 6.58 (dd, J = 8.3, 1.9 Hz, 1 H), 6.58 (d, J = 8.2 Hz, 1 H), 6.61 (d, J = 1.9 Hz, 1 H), 6.67 (td, J = 7.8, 1,2 Hz, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.8, 1.2 Hz, 1 H), 6.98 (d, J = 8.3 Hz, 1 H) |
이하, 참고 화합물 2를 사용하고, 참고 화합물 4-1의 제조 방법에 준하여, 참고 화합물 4-2를 얻었다.
5-(5-플루오르-2-메틸페닐아미노메틸)-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 4-2) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.09 (s, 3 H), 1.19 (s, 3 H), 1.89 (s, 3 H), 2.03 (s, 3 H), 3.38 (s, 3 H), 3.69 (s, 3 H), 3.93 (dd, J = 13.2, 5.0 Hz, 1 H), 4.06 (dd, J = 13.2, 4.3 Hz, 1 H), 4.17-4.19 (m, 1 H), 5.19 (s, 2 H), 5.39 (s, 1 H), 5.96 (s, 1 H), 6.05 (dd, J = 12.2, 2.6 Hz, 1 H), 6.20 (td, J = 8.5, 2.6 Hz, 1 H), 6.59 (d, J = 8.3 Hz, 1 H), 6.61 (dd, J = 8.5, 2.6 Hz, 1 H), 6.67 (d, J = 2.6 Hz, 1 H), 6.70 (d, J = 8.3 Hz, 1 H), 6.85-6.89 (m, 1 H), 7.07 (d, J = 8.5 Hz, 1 H) |
참고예 5
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1)
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-메톡시메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 3-1, 424 mg, 0.888 mmol)를 1, 4-디옥산(5 mL)에 용해하고, 4N 염화수소/1, 4-디옥산(666㎕)을 가하여, 실온에서 밤새 교반했다. 에틸아세테이트(150 mL)를 가하여 희석했다. 물 (100 mL, 2회) 및 포화 식염수(50 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (241.7 mg)를 무색 고체로서 얻었다. (수율 63%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.00 (s, 3 H), 1.14 (s, 3 H), 2.01 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 4.63 (d, J = 12.1 Hz, 1 H), 5.08 (d, J = 12.1 Hz, 1 H), 5.37 (s, 1 H), 5.90 (s, 1 H), 6.29 (dd, J = 11.5, 2.4 Hz, 1 H), 6.36 (dd, J = 8.1, 2.3 Hz, 1 H), 6.45 (d, J = 2.3 Hz, 1 H), 6.50 (td, J = 8.4, 2.4 Hz, 1 H), 6.58 (d, J = 8.1 Hz, 1 H), 6.73 (d, J = 8.1 Hz, 1 H), 6.94 (d, J = 8.1 Hz, 1 H), 7.00-7.04 (m, 1 H), 9.46 (s, 1 H) |
이하, 참고 화합물 3-2∼3-9 및 4-1∼4-2로부터 선택되는 화합물을 사용하고, 참고 화합물 5-1의 제조 방법에 준하여, 참고 화합물 5-2∼5-11을 얻었다.
5-(5-플루오르-2-메틸페녹시메틸)-6-(5-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-2) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.02 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.61 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.38 (s, 1 H), 5.99 (s, 1 H), 6.33 (dd, J = 11.5, 2.4 Hz, 1 H), 6.51 (td, J = 8.4, 2.4 Hz, 1 H), 6.59 (d, J = 2.9 Hz, 1 H), 6.61 (d, J = 8.3 Hz, 1 H), 6.67 (dd, J = 8.8, 2.9 Hz, 1 H), 6.75 (d, J = 8.3 Hz, 1 H), 6.85 (d, J = 8.8 Hz, 1 H), 7.00-7.04 (m, 1 H), 8.93 (s, 1 H) |
6-(4-하이드록시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-3) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.85 (s, 3 H), 1.17 (s, 3 H), 2.13 (s, 3 H), 2.18 (s, 3 H), 3.68 (s, 3 H), 4.79 (d, J = 12.5 Hz, 1 H), 5.30 (d, J = 12.5 Hz, 1 H), 5.37 (s, 1 H), 5.92 (s, 1 H), 6.40 (dd, J = 8.2, 2.3 Hz, 1 H), 6.46 (d, J = 2.3 Hz, 1 H), 6.57 (d, J = 8.3 Hz, 1 H), 6.74 (d, J = 8.3 Hz, 1 H), 7.05 (d, J = 8.2 Hz, 1 H), 7.11 (d, J = 2.3 Hz, 1 H), 7.32 (d, J = 8.3 Hz, 1 H), 7.62 (dd, J = 8.3, 2.3 Hz, 1 H), 9.50 (s, 1 H) |
6-(4-하이드록시-2-메톡시페닐)-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-4) |
1 H-NMR (400 MHz, CDCl3) δ 0.98 (s, 3 H), 1.17 (s, 3 H), 2.13 (s, 3 H), 3.63 (s, 3 H), 3.82 (s, 3 H), 4.67 (d, J = 12.0 Hz, 1 H), 5.24 (d, J = 12.0 Hz, 1 H), 5.36 (s, 1 H), 5.90 (s, 1 H), 6.28 (dd, J = 8.3, 2.2 Hz, 1 H), 6.40 (d, J = 2.2 Hz, 1 H), 6.58 (d, J = 8.2 Hz, 1 H), 6.71 (d, J = 8.2 Hz, 1 H), 6.94 (d, J = 8.3 Hz, 1 H), 7.08 (d, J = 9.2 Hz, 1 H), 7.28 (d, J = 2.8 Hz, 1 H), 7.79 (dd, J = 9.2, 2.8 Hz, 1 H), 9.40 (s, 1 H) |
6-(4-하이드록시-2-메톡시페닐)-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-5) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.06 (s, 3 H), 2.35 (s, 3 H), 3.60 (s, 3 H), 4.96 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.43 (s, 1 H), 6.00 (s, 1 H), 6.31 (dd, J = 8.2, 2.4 Hz, 1 H), 6.41 (d, J = 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.89 (d, J = 8.2 Hz, 1 H), 7.27 (d, J = 8.1 Hz, 2 H), 7.72 (d, J = 8.1 Hz, 2 H), 9.42 (s, 1 H) |
6-(4-하이드록시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-6) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 2.47 (s, 3 H), 3.60 (s, 3 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.15 (d, J = 12.7 Hz, 1 H), 5.42 (s, 1 H), 5.99 (s, 1 H), 6.31 (dd, J = 8.1, 2.1 Hz, 1 H), 6.42 (d, J = 2.1 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.72 (d, J = 8.2 Hz, 1 H), 6.88 (d, J = 8.1 Hz, 1 H), 6.88 (dd, J = 3.7, 1.1 Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H), 9.43 (s, 1 H) |
5-(3-플루오르벤조일옥시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-7) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 3.60 (s, 3 H), 5.03 (d, J = 12.8 Hz, 1 H), 5.23 (d, J = 12.8 Hz, 1 H), 5.45 (s, 1 H), 6.03 (s, 1 H), 6.32 (dd, J = 8.1, 2.4 Hz, 1 H), 6.42 (d, J = 2.4 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 6.90 (d, J = 8.1 Hz, 1 H), 7.48-7.57 (m, 3 H), 7.66-7.67 (m, 1 H), 9.43 (s, 1 H) |
5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-8) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 3.60 (s, 3 H), 4.95 (d, J = 12.6 Hz, 1 H), 5.18 (d, J = 12.6 Hz, 1 H), 5.44 (s, 1 H), 6.02 (s, 1 H), 6.32 (dd, J = 8.1, 2.3 Hz, 1 H), 6.41 (d, J = 2.3 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.72 (d, J = 8.3 Hz, 1 H), 6.88 (d, J = 8.1 Hz, 1 H), 7.33 (d, J = 4.0 Hz, 1 H), 7.49 (d, J = 4.0 Hz, 1 H), 9.44 (s, 1 H) |
6-(4-하이드록시-2-메톡시페닐)-5-(4-메톡시벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-9) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.06 (s, 3 H), 3.60 (s, 3 H), 3.81 (s, 3 H), 4.94 (d, J = 12.7 Hz, 1 H), 5.16 (d, J = 12.7 Hz, 1 H), 5.43 (s, 1 H), 5.99 (s, 1 H), 6.31 (dd, J = 8.0, 2.2 Hz, 1 H), 6.41 (d, J = 2.2 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.89 (d, J = 8.0 Hz, 1 H), 6.99 (dt, J = 9.2, 2.2 Hz, 2 H), 7.78 (dt, J = 9.2, 2.2 Hz, 2 H), 9.41 (s, 1 H) |
6-(4-하이드록시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-10) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 3.59 (s, 3 H), 3.71 (s, 3 H), 3.83 (dd, J = 12.2, 3.4 Hz, 1 H), 4.02 (dd, J = 12.2, 6.7 Hz, 1 H), 4.23 (dd, J = 6.7, 3.4 Hz, 1 H), 5.37 (s, 1 H), 5.90 (s, 1 H), 6.31 (dd, J = 8.2, 2.2 Hz, 1 H), 6.35 (dd, J = 7.7, 1.6 Hz, 1 H), 6.36 (d, J = 2.2 Hz, 1 H), 6.50 (td, J = 7.7, 1.6 Hz, 1 H), 6.56 (d, J = 8.1 Hz, 1 H), 6.66 (d, J = 8.1 Hz, 1 H), 6.68 (td, J = 7.7, 1.2 Hz, 1 H), 6.73 (dd, J = 7.7, 1.2 Hz, 1 H), 6.84 (d, J = 8.2 Hz, 1 H), 9.36 (s, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-11) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.09 (s, 3 H), 1.19 (s, 3 H), 1.89 (s, 3 H), 2.04 (s, 3 H), 3.65 (s, 3 H), 3.93 (dd, J = 13.3, 6.7 Hz, 1 H), 4.02-4.07 (m, 1 H), 4.14-4.17 (m, 1 H), 5.39 (s, 1 H), 5.93 (s, 1 H), 6.06 (dd, J = 12.1, 2.5 Hz, 1 H), 6.20 (td, J = 8.4, 2.5 Hz, 1 H), 6.35 (dd, J = 8.1, 2.2 Hz, 1 H), 6.42 (d, J = 2.2 Hz, 1 H), 6.57 (d, J = 8.2 Hz, 1 H), 6.69 (d, J = 8.2 Hz, 1 H), 6.86-6.89 (m, 1 H), 6.93 (d, J = 8.1 Hz, 1 H), 9.41 (s, 1 H) |
참고예 6
6-(4-하이드록시-2-메톡시페닐)-5-[N-(2-메톡시페닐)-N-(9-플루오레닐메톡시카르보닐)아미노메틸]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 6)
6-(4-하이드록시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-10, 37.7 mg, 0.0876 mmol) 및 탄산수소나트륨(9.5 mg, 0.113 mmol)를 1, 4-디옥산(0.5 mL)-물 (0.5 mL)에 용해하고, 빙랭하, 염화 9-플루오레닐메톡시카르보닐(25.6 mg, 0.0990 mmol)를 가하였다. 반응액을 실온에서 3시간 교반한 후, 에틸아세테이트(10 mL)를 가하여 희석했다. 1N 염산 수용액(10 mL), 물 (10 mL) 및 포화 식염수(10 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 참고 화합물 (19.7 mg)를 무색 아몰퍼스로서 얻었다. (수율 34%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.22 (s, 3 H), 1.28 (s, 3 H), 2.20 (s, 3 H), 3.29 (s, 3 H), 3.61 (s, 3 H), 3.89 (s, 2 H), 5.30 (d, J = 14.3 Hz, 1 H), 5.45 (s, 1 H), 5.81 (d, J = 14.3 Hz, 1 H), 5.85 (s, 1 H), 6.22 (dd, J = 8.2, 2.1 Hz, 1 H), 6.34-6.35 (m, 2 H), 6.43 (d, J = 8.3 Hz, 1 H), 6.63-6.65 (m, 2 H), 6.87-6.91 (m, 3 H), 7.09-7.25 (m, 4 H), 7.31-7.35 (m, 2 H), 7.79 (d, J = 7.6 Hz, 2 H), 9.32 (s, 1 H) |
실시예 1
6-(4-벤조일옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-1)
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1, 25.5 mg, 0.588 mmol)를 무수 테트라하이드로퓨란(0.5 mL)에 용해하고, 트리에틸아민(19.7 ㎕, 0.141 mmol) 및 염화 벤조일(8.2 ㎕, 0.071 mmol)를 가하였다. 반응액을 실온에서 30분간 교반했다. 반응액에 에틸아세테이트(100 mL)를 가하여 희석했다. 물 (100 mL), 포화 식염수(50 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (26.7 mg)를 무색 고체로서 얻었다. (수율 63%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.2, 2.3 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.05 (d, J = 2.3 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.62 (t, J = 7.4 Hz, 2 H), 7.76 (t, J = 7.4 Hz, 1 H), 8.15 (d, J = 7.4 Hz, 2 H) |
6-(4-t-부톡시카르보닐아미노아세톡시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-2)
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1, 30.2 mg, 0.070 mmol), Boc-글리신(15.1 mg, 0.086 mmol)를 N,N-디메틸포름아미드(1 ml)에 용해하고, N,N-디이소프로필 에틸아민(31.4 ㎕, 0.18 mmol)와 O-(7-아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄 헥사플루오로포스페이트(35.4 mg, 0.093 mmol)를 가하여, 실온에서 밤새 교반했다. 반응액에 에틸아세테이트(10 ml)를 가하여, 물 (10 ml), 포화 식염수(10 ml)로 순차적으로 세정하였다. 유기층을 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (35.3 mg)를 무색 아몰퍼스로서 얻었다. (수율 86%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 1.40 (s, 9 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.71 (s, 3 H), 3.96 (d, J = 6.0 Hz, 2 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.04 (s, 1 H), 6.34 (d, J = 11.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.71 (dd, J = 8.3, 2.3 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.83 (d, J = 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.19 (d, J = 8.3 Hz, 1 H), 7.40 (t, J = 6.0 Hz, 1 H) |
6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-3)
6-(4-하이드록시-2-메톡시페닐)-5-[N-(2-메톡시페닐)-N-(9-플루오레닐메톡시카르보닐)아미노메틸]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 6, 17.4 mg, 0.0267 mmol)를 디클로로메탄(0.5 mL)에 용해하고, 트리에틸아민(10 ㎕, 0.072 mmol) 및 염화 2-프로일(3.6 ㎕, 0.036 mmol)를 순차적으로 가하였다. 반응액을 실온에서 3시간 교반한 후, 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제해 무색 아몰퍼스(15.6 mg)를 얻었다. 얻어진 무색 아몰퍼스(11.8 mg)를 N,N-디메틸포름아미드(0.3 mL)에 용해하고, 피페리딘(15.6 ㎕, 0.158 mmol)를 가하였다. 반응액을 실온에서 1분간 교반한 후, 에틸아세테이트(10 mL)로 희석했다. 물 (10 mL) 및 포화 식염수(10 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (6.0 mg)를 무색 고체로서 얻었다. (수율 76%)
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.66 (s, 3 H), 3.72 (s, 3 H), 3.85 (dd, J = 12.5, 3.3 Hz, 1 H), 4.05 (dd, J = 12.5, 6.5 Hz, 1 H), 4.24 (dd, J = 6.5, 3.3 Hz, 1 H), 5.40 (s, 1 H), 6.01 (s, 1 H), 6.37 (d, J = 7.8 Hz, 1 H), 6.51 (t, J = 7.8 Hz, 1 H), 6.61 (d, J = 8.2 Hz, 1 H), 6.68 (t, J = 7.8 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.74 (d, J = 7.8 Hz, 1 H), 6.79 (dd, J = 3.8, 1.3 Hz, 1 H), 6.83 (dd, J = 8.0, 2.2 Hz, 1 H), 6.93 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 1 H), 7.55 (d, J = 3.8 Hz, 1 H), 8.10 (d, J = 1.3 Hz, 1 H) |
이하, 참고 화합물 5-1∼5-11 및 6으로부터 선택되는 화합물을 사용하고, 화합물 1-1∼1-3 중 어느 하나의 제조 방법에 준하여, 화합물 1-4∼1-175를 얻었다.
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메톡시벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-4) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 3.88 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.37 (dd, J = 11.3, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 7.9 Hz, 1 H), 6.81 (d, J = 7.9 Hz, 1 H), 6.86 (dd, J = 8.1, 2.1 Hz, 1 H), 7.01 (d, J = 2.1 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.13 (d, J = 8.9 Hz, 2 H), 7.22 (d, J = 8.1 Hz, 1 H), 8.10 (d, J = 8.9 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메톡시벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-5) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 3.86 (s, 3 H), 4.65 (d, J = 12.0 Hz, 1 H), 5.10 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.5, 2.5 Hz, 1 H), 6.54 (td, J = 8.4, 2.5 Hz, 1 H), 6.65 (d, J = 8.1 Hz, 1 H), 6.81 (d, J = 8.1 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.05 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.31-7.34 (m, 1 H), 7.53 (t, J = 7.9 Hz, 1 H), 7.62 (dd, J = 2.4, 1.5 Hz, 1 H), 7.72-7.75 (m, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-6) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 3.88 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.37 (dd, J = 11.4, 2.6 Hz, 1 H), 6.53 (td, J = 8.3, 2.4 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.84 (dd, J = 8.3, 2.2 Hz, 1 H), 6.98 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.10 (t, J = 7.5 Hz, 1 H), 7.23 (d, J = 8.3 Hz, 1 H), 7.23 (d, J = 7.5 Hz, 1 H), 7.64 (t, J = 7.5 Hz, 1 H), 7.93 (d, J = 7.5 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-7) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.75 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.91 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.07 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.54-7.58 (m, 1 H), 7.67-7.69 (m, 2 H), 8.10-8.12 (m, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-8) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.4, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.11 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.66 (ddd, J = 8.0, 4.9, 0.8 Hz, 1 H), 8.48 (dt, J = 8.0, 2.0 Hz, 1 H), 8.91 (dd, J = 4.9, 2.0 Hz, 1 H), 9.27 (dd, J = 2.0, 0.8 Hz, 1 H) |
6-(4-부틸릴옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-9) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.98 (t, J = 7.3 Hz, 3 H), 1.05 (s, 3 H), 1.15 (s, 3 H), 1.64-1.70 (m, 2 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 2.55 (t, J = 7.3 Hz, 2 H), 3.71 (s, 3 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.07 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.71 (dd, J = 8.2, 2.2 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.84 (d, J = 2.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.17 (d, J = 8.2 Hz, 1 H) |
6-(4-아세톡시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-10) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 2.26 (s, 3 H), 3.71 (s, 3 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.07 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.33 (dd, J = 11.6, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.1 Hz, 1 H), 6.72 (dd, J = 8.2, 2.1 Hz, 1 H), 6.78 (d, J = 8.1 Hz, 1 H), 6.86 (d, J = 2.1 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.17 (d, J = 8.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-프로피오닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-11) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.14 (t, J = 7.5 Hz, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 2.59 (q, J = 7.5 Hz, 2 H), 3.71 (s, 3 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.72 (dd, J = 8.1, 2.2 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.85 (d, J = 2.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.17 (d, J = 8.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-12) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.73 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.37 (dd, J = 11.3, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.2, 2.2 Hz, 1 H), 7.01 (d, J = 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.62 (dd, J = 5.0, 1.2 Hz, 1 H), 7.75 (dd, J = 5.0, 3.0 Hz, 1 H), 8.60 (dd, J = 3.0, 1.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-13) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.73 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.81 (dd, J = 3.6, 1.8 Hz, 1 H), 6.86 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.57 (d, J = 3.6 Hz, 1 H), 8.11 (d, J = 1.8 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소부틸릴옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-14) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 1.24 (d, J = 7.0 Hz, 6 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 2.81 (sept, J = 7.0 Hz, 1 H), 3.72 (s, 3 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.35 (dd, J = 11.5, 2.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.71 (dd, J = 8.3, 2.2 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.83 (d, J = 2.2 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.18 (d, J = 8.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-페닐아세톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-15) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.14 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.71 (s, 3 H), 3.96 (s, 2 H), 4.60 (d, J = 12.2 Hz, 1 H), 5.06 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.33 (dd, J = 11.5, 2.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.71 (dd, J = 8.1, 2.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.85 (d, J = 2.2 Hz, 1 H), 7.01-7.04 (m, 1 H), 7.17 (d, J = 8.1 Hz, 1 H), 7.28-7.32 (m, 1 H), 7.35-7.40 (m, 4 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-16) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.10 (s, 3 H), 1.13 (s, 3 H), 1.98 (s, 3 H), 2.06 (s, 3 H), 3.75 (s, 3 H), 4.63 (d, J = 11.8 Hz, 1 H), 5.09 (d, J = 11.8 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.43 (dd, J = 11.3, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.84 (d, J = 8.2 Hz, 1 H), 6.97-7.00 (m, 1 H), 7.05 (d, J = 2.9 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.18 (dd, J = 8.9, 2.9 Hz, 1 H), 7.54 (dd, J = 5.1, 1.2 Hz, 1 H), 7.73 (dd, J = 5.1, 3.0 Hz, 1 H), 8.51 (dd, J = 3.0, 1.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[5-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-17) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.10 (s, 3 H), 1.13 (s, 3 H), 1.99 (s, 3 H), 2.06 (s, 3 H), 3.75 (s, 3 H), 4.64 (d, J = 12.3 Hz, 1 H), 5.08 (d, J = 12.3 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.42 (dd, J = 11.5, 2.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.79 (dd, J = 3.6, 1.7 Hz, 1 H), 6.83 (d, J = 8.3 Hz, 1 H), 6.97-7.00 (m, 1 H), 7.06 (d, J = 2.9 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.19 (dd, J = 8.9, 2.9 Hz, 1 H), 7.48 (dd, J = 3.6, 0.7 Hz, 1 H), 8.08 (dd, J = 1.7, 0.7 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-5-프로피오닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-18) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.09 (t, J = 7.5 Hz, 3 H), 1.09 (s, 3 H), 1.13 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 2.49-2.53 (m, 2 H), 3.72 (s, 3 H), 4.60 (d, J = 11.9 Hz, 1 H), 5.07 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.40 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.92 (d, J = 2.4 Hz, 1 H), 7.02-7.06 (m, 3 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-19) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.12 (s, 3 H), 1.13 (s, 3 H), 1.98 (s, 3 H), 2.06 (s, 3 H), 3.76 (s, 3 H), 4.62 (d, J = 11.9 Hz, 1 H), 5.09 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.08 (s, 1 H), 6.46 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.85 (d, J = 8.2 Hz, 1 H), 6.94-6.98 (m, 1 H), 7.13 (d, J = 2.9 Hz, 1 H), 7.13 (d, J = 9.0 Hz, 1 H), 7.25 (dd, J = 9.0, 2.9 Hz, 1 H), 7.65 (ddd, J = 8.1, 4.9, 1.1 Hz, 1 H), 8.38 (dt, J = 8.1, 1.9 Hz, 1 H), 8.89 (dd, J = 4.9, 1.9 Hz, 1 H), 9.18 (t, J = 1.1 Hz, 1 H) |
6-(5-부틸릴옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-20) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.94 (t, J = 7.3 Hz, 3 H), 1.09 (s, 3 H), 1.14 (s, 3 H), 1.57-1.66 (m, 2 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 2.49-2.52 (m, 2 H), 3.72 (s, 3 H), 4.59 (d, J = 12.0 Hz, 1 H), 5.07 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.40 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.91 (d, J = 2.4 Hz, 1 H), 7.01-7.07 (m, 3 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(5-이소부틸릴옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-21) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.08 (s, 3 H), 1.14 (s, 3 H), 1.17 (d, J = 7.1 Hz, 6 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 2.73 (sept, J = 7.1 Hz, 1 H), 3.72 (s, 3 H), 4.57 (d, J = 11.9 Hz, 1 H), 5.08 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.40 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.80 (d, J = 8.1 Hz, 1 H), 6.90 (d, J = 2.7 Hz, 1 H), 7.01-7.07 (m, 3 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-22) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.88 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.32 (dd, J = 5.0, 3.9 Hz, 1 H), 8.03 (dd, J = 3.9, 1.3 Hz, 1 H), 8.10 (dd, J = 5.0, 1.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-5-페닐아세톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-23) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.09 (s, 3 H), 1.13 (s, 3 H), 1.99 (s, 3 H), 2.05 (s, 3 H), 3.72 (s, 3 H), 3.88 (s, 2 H), 4.58 (d, J = 11.9 Hz, 1 H), 5.06 (d, J = 11.9 Hz, 1 H), 5.39 (s, 1 H), 6.06 (s, 1 H), 6.39 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.5, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.90 (d, J = 2.0 Hz, 1 H), 7.01-7.05 (m, 3 H), 7.28-7.38 (m, 5 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-페닐프로피오닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-24) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.14 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 2.88-2.92 (m, 2 H), 2.96-3.00 (m, 2 H), 3.69 (s, 3 H), 4.60 (d, J = 12.1 Hz, 1 H), 5.06 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.64 (dd, J = 8.1, 2.2 Hz, 1 H), 6.73 (d, J = 2.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.16 (d, J = 8.1 Hz, 1 H), 7.20-7.24 (m, 1 H), 7.29-7.34 (m, 4 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-25) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.73 (s, 3 H), 4.62 (d, J = 12.2 Hz, 1 H), 5.08 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.2, 2.2 Hz, 1 H), 6.94 (dd, J = 1.7, 0.9 Hz, 1 H), 6.98 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.92 (t, J = 1.7 Hz, 1 H), 8.64 (dd, J = 1.7, 0.9 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-26) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.66 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.91 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.06 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.74 (ddd, J = 7.7, 4.7, 1.1 Hz, 1 H), 8.09 (td, J = 7.7, 1.7 Hz, 1 H), 8.25 (dt, J = 7.7, 1.1 Hz, 1 H), 8.82 (ddd, J = 4.7, 1.7, 1.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-27) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.13 (s, 3 H), 1.99 (s, 3 H), 2.06 (s, 3 H), 3.75 (s, 3 H), 4.61 (d, J = 12.4 Hz, 1 H), 5.09 (d, J = 12.4 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.44 (dd, J = 11.4, 2.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.84 (d, J = 8.3 Hz, 1 H), 6.96-7.01 (m, 1 H), 7.07 (d, J = 2.9 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.20 (dd, J = 8.9, 2.9 Hz, 1 H), 7.30 (dd, J = 5.0, 3.8 Hz, 1 H), 7.94 (dd, J = 3.8, 1.3 Hz, 1 H), 8.07 (dd, J = 5.0, 1.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[5-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로키노리(화합물 1-28) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.10 (s, 3 H), 1.13 (s, 3 H), 1.99 (s, 3 H), 2.06 (s, 3 H), 3.74 (s, 3 H), 4.63 (d, J = 12.4 Hz, 1 H), 5.08 (d, J = 12.4 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.42 (dd, J = 11.5, 2.5 Hz, 1 H), 6.53 (td, J = 8.5, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.83 (d, J = 8.2 Hz, 1 H), 6.87 (dd, J = 1.7, 0.9 Hz, 1 H), 6.98-7.01 (m, 1 H), 7.04 (d, J = 2.9 Hz, 1 H), 7.10 (d, J = 9.0 Hz, 1 H), 7.17 (dd, J = 9.0, 2.9 Hz, 1 H), 7.89 (t, J = 1.7 Hz, 1 H), 8.55 (dd, J = 1.7, 0.9 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-니트로벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-29) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.75 (s, 3 H), 4.64 (d, J = 12.2 Hz, 1 H), 5.09 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.4, 2.3 Hz, 1 H), 6.53 (td, J = 8.5, 2.3 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.3, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.28 (d, J = 8.3 Hz, 1 H), 7.92 (td, J = 7.7, 1.4 Hz, 1 H), 7.96 (td, J = 7.7, 1.4 Hz, 1 H), 8.13 (dd, J = 7.7, 1.4 Hz, 1 H), 8.19 (dd, J = 7.7, 1.4 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-니트로벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-30) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.75 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.11 (d, J = 12.1 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.39 (dd, J = 11.5, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.95 (dd, J = 8.3, 2.2 Hz, 1 H), 7.03-7.07 (m, 1 H), 7.13 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.3 Hz, 1 H), 7.93 (t, J = 7.9 Hz, 1 H), 8.54-8.56 (m, 1 H), 8.58-8.61 (m, 1 H), 8.81 (t, J = 2.0 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-니트로벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-31) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.4, 2.3 Hz, 1 H), 6.54 (td, J = 8.4, 2.3 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.95 (dd, J = 8.3, 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.12 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.3 Hz, 1 H), 8.38 (d, J = 9.0 Hz, 2 H), 8.43 (d, J = 9.0 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-메톡시아세톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-32) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.40 (s, 3 H), 3.72 (s, 3 H), 4.33 (s, 2 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.07 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.04 (s, 1 H), 6.35 (dd, J = 11.5, 2.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.63 (d, J = 8.4 Hz, 1 H), 6.77 (dd, J = 8.1, 2.1 Hz, 1 H), 6.78 (d, J = 8.4 Hz, 1 H), 6.91 (d, J = 2.1 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.19 (d, J = 8.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-33) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.3, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.93 (dd, J = 8.2, 2.4 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.11 (d, J = 2.4 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 8.02 (d, J = 6.0 Hz, 2 H), 8.89 (d, J = 6.0 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(피리딘-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-34) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.10 (s, 3 H), 1.13 (s, 3 H), 1.98 (s, 3 H), 2.06 (s, 3 H), 3.76 (s, 3 H), 4.67 (d, J = 12.0 Hz, 1 H), 5.09 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.08 (s, 1 H), 6.43 (dd, J = 11.6, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.85 (d, J = 8.3 Hz, 1 H), 6.95-6.99 (m, 1 H), 7.11 (d, J = 2.9 Hz, 1 H), 7.13 (d, J = 9.0 Hz, 1 H), 7.23 (dd, J = 9.0, 2.9 Hz, 1 H), 7.73 (ddd, J = 7.7, 4.8, 1.1 Hz, 1 H), 8.07 (td, J = 7.7, 1.7 Hz, 1 H), 8.15 (dt, J = 7.7, 1.1 Hz, 1 H), 8.80 (ddd, J = 4.8, 1.7, 1.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-35) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.12 (s, 3 H), 1.13 (s, 3 H), 1.98 (s, 3 H), 2.06 (s, 3 H), 3.76 (s, 3 H), 4.61 (d, J = 11.8 Hz, 1 H), 5.09 (d, J = 11.8 Hz, 1 H), 5.40 (s, 1 H), 6.09 (s, 1 H), 6.45 (dd, J = 11.4, 2.4 Hz, 1 H), 6.53 (td, J = 8.3, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.85 (d, J = 8.3 Hz, 1 H), 6.96-6.99 (m, 1 H), 7.13 (d, J = 2.9 Hz, 1 H), 7.13 (d, J = 9.0 Hz, 1 H), 7.26 (dd, J = 9.0, 2.9 Hz, 1 H), 7.92 (d, J = 6.1 Hz, 2 H), 8.88 (d, J = 6.1 Hz, 2 H) |
6-[4-(2-아세톡시벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-36) |
1 H-NMR (500 MHz, CDCl3) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.08 (s, 3 H), 2.17 (s, 3 H), 2.32 (s, 3 H), 3.76 (s, 3 H), 4.75 (d, J = 11.9 Hz, 1 H), 5.12 (d, J = 11.9 Hz, 1 H), 5.46 (s, 1 H), 6.21 (dd, J = 11.0, 2.4 Hz, 1 H), 6.43 (td, J = 8.4, 2.4 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.78 (d, J = 2.1 Hz, 1 H), 6.81 (dd, J = 8.1, 2.1 Hz, 1 H), 6.92 (d, J = 8.1 Hz, 1 H), 6.93-6.95 (m, 1 H), 7.19 (dd, J = 7.9, 1.4 Hz, 1 H), 7.29 (d, J = 8.1 Hz, 1 H), 7.40 (td, J = 7.9, 1.4 Hz, 1 H), 7.65 (td, J = 7.9, 1.4 Hz, 1 H), 8.24 (dd, J = 7.9, 1.4 Hz, 1 H) |
6-[4-(1-t-부톡시카르보닐피페리딘-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-37) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 1.53-1.62 (m, 2 H), 1.95-1.96 (m, 2 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 2.81-2.84 (m, 1 H), 2.91-2.93 (m, 2 H), 3.72 (s, 3 H), 3.89-3.92 (m, 2 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.1 Hz, 1 H), 6.73 (dd, J = 8.3, 2.2 Hz, 1 H), 6.78 (d, J = 8.1 Hz, 1 H), 6.86 (d, J = 2.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.18 (d, J = 8.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-38) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.47 (s, 3 H), 3.74 (s, 3 H), 4.66 (d, J = 12.2 Hz, 1 H), 5.11 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.87 (dd, J = 8.0, 2.4 Hz, 1 H), 7.02 (d, J = 2.4 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.24 (d, J = 8.0 Hz, 1 H), 7.31-7.35 (m, 1 H), 7.47 (d, J = 7.9 Hz, 1 H), 7.66-7.69 (m, 1 H), 8.19 (dd, J = 7.6, 1.5 Hz, 1 H) |
6-[4-(1-t-부톡시카르보닐이미다졸-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-39) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 1.61 (s, 9 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.73 (s, 3 H), 4.63 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.85 (dd, J = 8.3, 2.2 Hz, 1 H), 6.99 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.22 (d, J = 8.3 Hz, 1 H), 8.37 (d, J = 1.2 Hz, 1 H), 8.41 (d, J = 1.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-40) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.2, 2.5 Hz, 1 H), 6.53 (td, J = 8.4, 2.5 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.89 (dd, J = 8.3, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.04 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.3 Hz, 1 H), 8.88 (d, J = 1.9 Hz, 1 H), 9.28 (d, J = 1.9 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티아졸-5-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물1-41) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.74 (s, 3 H), 4.63 (d, J = 12.2 Hz, 1 H), 5.09 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.2, 2.5 Hz, 1 H), 6.53 (td, J = 8.5, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.91 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.08 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 8.76 (d, J = 0.7 Hz, 1 H), 9.49 (d, J = 0.7 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(옥사졸-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-42) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.73 (s, 3 H), 4.63 (d, J = 12.4 Hz, 1 H), 5.09 (d, J = 12.4 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.2, 2.3 Hz, 1 H), 7.01 (d, J = 2.3 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 8.67 (d, J = 1.0 Hz, 1 H), 9.14 (d, J = 1.0 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(5-메틸티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-43) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 2.57 (s, 3 H), 3.74 (s, 3 H), 4.63 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.4, 2.5 Hz, 1 H), 6.53 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.85 (dd, J = 8.3, 2.4 Hz, 1 H), 7.00 (d, J = 2.4 Hz, 1 H), 7.02-7.06 (m, 2 H), 7.22 (d, J = 8.3 Hz, 1 H), 7.85 (d, J = 3.4 Hz, 1 H) |
6-[4-(3-아세틸벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-44) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.68 (s, 3 H), 3.75 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.11 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.39 (dd, J = 11.3, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.1 Hz, 1 H), 6.82 (d, J = 8.1 Hz, 1 H), 6.93 (dd, J = 8.1, 2.1 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.09 (d, J = 2.1 Hz, 1 H), 7.25 (d, J = 8.1 Hz, 1 H), 7.79 (t, J = 7.9 Hz, 1 H), 8.32 (dt, J = 7.9, 1.5 Hz, 1 H), 8.38 (dt, J = 7.9, 1.5 Hz, 1 H), 8.68 (t, J = 1.5 Hz, 1 H) |
6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-45) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.4, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.90 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.06 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.41-7.47 (m, 2 H), 7.76-7.81 (m, 1 H), 8.12 (td, J = 7.8, 1.7 Hz, 1 H) |
6-[4-(3-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-46) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.4, 2.5 Hz, 1 H), 6.54 (td, J = 8.2, 2.5 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.91 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.08 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.63 (tdd, J = 8.5, 2.6, 1.2 Hz, 1 H), 7.66-7.71 (m, 1 H), 7.88-7.91 (m, 1 H), 8.00 (dt, J = 7.5, 1.4 Hz, 1 H) |
6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-47) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.3, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.1, 2.1 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.06 (d, J = 2.1 Hz, 1 H), 7.24 (d, J = 8.1 Hz, 1 H), 7.44-7.47 (m, 2 H), 8.20-8.23 (m, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(5-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-48) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 2.42 (s, 3 H), 3.73 (s, 3 H), 4.63 (d, J = 12.0 Hz, 1 H), 5.08 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.45 (d, J = 3.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.80 (d, J = 8.1 Hz, 1 H), 6.84 (dd, J = 8.3, 2.3 Hz, 1 H), 6.98 (d, J = 2.3 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.21 (d, J = 8.3 Hz, 1 H), 7.47 (d, J = 3.4 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-49) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.80 (s, 3 H), 3.75 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.11 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.2, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.1 Hz, 1 H), 6.81 (d, J = 8.1 Hz, 1 H), 6.92 (dd, J = 8.2, 2.3 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.09 (d, J = 2.3 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.47 (dd, J = 7.9, 4.7 Hz, 1 H), 8.45 (dd, J = 7.9, 1.7 Hz, 1 H), 8.72 (dd, J = 4.7, 1.7 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-3-일아세톡시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-50) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.14 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.71 (s, 3 H), 4.05 (s, 2 H), 4.60 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.04 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.5, 2.4 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.75 (dd, J = 8.2, 2.3 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.89 (d, J = 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.40 (dd, J = 7.8, 4.8 Hz, 1 H), 7.47 (dt, J = 7.8, 2.0 Hz, 1 H), 8.50 (dd, J = 4.8, 2.0 Hz, 1 H), 8.59 (d, J = 2.0 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메틸티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-51) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.56 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.37 (dd, J = 11.5, 2.5 Hz, 1 H), 6.53 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.85 (dd, J = 8.2, 2.2 Hz, 1 H), 7.00 (d, J = 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.17 (d, J = 5.1 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.93 (d, J = 5.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메틸티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-52) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.30 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.4 Hz, 1 H), 5.10 (d, J = 12.4 Hz, 1 H), 5.41 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.3, 2.5 Hz, 1 H), 6.54 (td, J = 8.5, 2.5 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.87 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.04-7.07 (m, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.69-7.70 (m, 1 H), 7.87 (d, J = 1.2 Hz, 1 H) |
6-[4-(4-아세틸벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-53) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.67 (s, 3 H), 3.74 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.92 (dd, J = 8.3, 2.2 Hz, 1 H), 7.03-7.07 (m, 1 H), 7.09 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.3 Hz, 1 H), 8.14-8.17 (m, 2 H), 8.25-8.28 (m, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-54) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 3.92 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.11 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.39 (dd, J = 11.5, 2.4 Hz, 1 H), 6.54 (td, J = 8.3, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.10 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.79 (t, J = 7.9 Hz, 1 H), 8.31 (dt, J = 7.9, 1.6 Hz, 1 H), 8.40 (dt, J = 7.9, 1.6 Hz, 1 H), 8.66 (t, J = 1.6 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-55) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 2.61 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.38 (dd, J = 11.4, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.91 (dd, J = 8.1, 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.08 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.1 Hz, 1 H), 7.51 (d, J = 8.1 Hz, 1 H), 8.35 (dd, J = 8.1, 2.2 Hz, 1 H), 9.14 (d, J = 2.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-56) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.16 (s, 3 H), 2.04 (s, 3 H), 2.09 (s, 3 H), 2.64 (s, 3 H), 3.76 (s, 3 H), 4.66 (d, J = 12.2 Hz, 1 H), 5.11 (d, J = 12.2 Hz, 1 H), 5.41 (s, 1 H), 6.05 (s, 1 H), 6.39 (dd, J = 11.3, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.66 (d, J = 8.1 Hz, 1 H), 6.82 (d, J = 8.1 Hz, 1 H), 6.95 (dd, J = 8.0, 2.2 Hz, 1 H), 7.04-7.07 (m, 1 H), 7.12 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.0 Hz, 1 H), 7.48 (d, J = 5.1 Hz, 1 H), 8.69 (d, J = 5.1 Hz, 1 H), 9.19 (s, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-57) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 2.38 (s, 3 H), 3.73 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.4, 2.5 Hz, 1 H), 6.53 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.70 (d, J = 1.7 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.3, 2.2 Hz, 1 H), 7.01 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.22 (d, J = 8.3 Hz, 1 H), 7.96 (d, J = 1.7 Hz, 1 H) |
6-(4-t-부틸카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-58) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 1.31 (s, 9 H), 2.02 (s, 3 H), 2.06 (s, 3 H), 3.73 (s, 3 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.07 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.35 (dd, J = 11.3, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.69 (dd, J = 8.1, 2.3 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 2.3 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.18 (d, J = 8.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시카르보닐벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-59) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.75 (s, 3 H), 3.85 (s, 3 H), 4.64 (d, J = 12.2 Hz, 1 H), 5.09 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.3, 2.4 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 7.00 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.26 (d, J = 8.2 Hz, 1 H), 7.75-7.80 (m, 2 H), 7.85-7.87 (m, 1 H), 7.96-7.99 (m, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메톡시카르보닐벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-60) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 3.92 (s, 3 H), 4.65 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.54 (td, J = 8.3, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03-7.07 (m, 1 H), 7.09 (d, J = 2.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 8.17 (d, J = 8.6 Hz, 2 H), 8.28 (d, J = 8.6 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리미딘-5-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-61) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.39 (dd, J = 11.3, 2.5 Hz, 1 H), 6.54 (td, J = 8.3, 2.5 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.95 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03-7.06 (m, 1 H), 7.13 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.2 Hz, 1 H), 9.44 (s, 2 H), 9.51 (s, 1 H) |
6-[4-(3-클로로티오펜-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-62) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.3 Hz, 1 H), 5.10 (d, J = 12.3 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.4, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.04 (d, J = 2.3 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.36 (d, J = 5.1 Hz, 1 H), 8.15 (d, J = 5.1 Hz, 1 H) |
6-[4-(5-클로로티오펜-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-63) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.73 (s, 3 H), 4.62 (d, J = 12.1 Hz, 1 H), 5.08 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.1, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.04 (d, J = 2.2 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 1 H), 7.39 (d, J = 4.2 Hz, 1 H), 7.93 (d, J = 4.2 Hz, 1 H) |
6-[4-(5-브로모퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-64) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.73 (s, 3 H), 4.62 (d, J = 12.1 Hz, 1 H), 5.08 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.37 (dd, J = 11.4, 2.5 Hz, 1 H), 6.53 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.87 (dd, J = 8.3, 2.3 Hz, 1 H), 6.97 (d, J = 3.7 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.03 (d, J = 2.3 Hz, 1 H), 7.22 (d, J = 8.3 Hz, 1 H), 7.61 (d, J = 3.7 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(5-니트로퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-65) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.16 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.63 (d, J = 12.2 Hz, 1 H), 5.09 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.2, 2.5 Hz, 1 H), 6.54 (td, J = 8.4, 2.5 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.09 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.2 Hz, 1 H), 7.84 (d, J = 3.9 Hz, 1 H), 7.89 (d, J = 3.9 Hz, 1 H) |
6-[4-(2-클로로-6-메틸피리딘-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-66) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.17 (s, 3 H), 2.02 (s, 3 H), 2.08 (s, 3 H), 2.60 (s, 3 H), 3.73 (s, 3 H), 4.62 (d, J = 12.0 Hz, 1 H), 5.09 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.4, 2.3 Hz, 1 H), 6.54 (td, J = 8.4, 2.3 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.94 (dd, J = 8.3, 2.3 Hz, 1 H), 7.02-7.07 (m, 1 H), 7.11 (d, J = 2.3 Hz, 1 H), 7.26 (d, J = 8.3 Hz, 1 H), 7.88 (d, J = 1.0 Hz, 1 H), 7.93 (d, J = 1.0 Hz, 1 H) |
6-[4-(3-클로로피리딘-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-67) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.63 (d, J = 12.1 Hz, 1 H), 5.09 (d, J = 12.1 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.4, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.95 (dd, J = 8.3, 2.2 Hz, 1 H), 7.03-7.07 (m, 1 H), 7.13 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.3 Hz, 1 H), 8.03 (dd, J = 5.0, 1.8 Hz, 1 H), 8.10 (dd, J = 1.8, 0.7 Hz, 1 H), 8.72 (dd, J = 5.0, 0.7 Hz, 1 H) |
6-[4-(2-클로로피리딘-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-68) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.75 (s, 3 H), 4.64 (d, J = 12.0 Hz, 1 H), 5.10 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.5, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.95 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.11 (d, J = 2.2 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 1 H), 8.06 (d, J = 4.9 Hz, 1 H), 8.79 (d, J = 4.9 Hz, 1 H), 8.91 (s, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(3-플루오르피리딘-4-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-69) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.16 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 4.64 (d, J = 12.2 Hz, 1 H), 5.10 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.38 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.3, 2.4 Hz, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.94 (dd, J = 8.2, 2.3 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.11 (d, J = 2.3 Hz, 1 H), 7.26 (d, J = 8.2 Hz, 1 H), 8.03-8.05 (m, 1 H), 8.70 (d, J = 4.9 Hz, 1 H), 8.88 (d, J = 2.2 Hz, 1 H) |
6-(4-부틸릴옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-70) |
1 H-NMR (500 MHz, DMSO-D6) δ 0.90 (s, 3 H), 0.98 (t, J = 7.5 Hz, 3 H), 1.18 (s, 3 H), 1.63-1.69 (m, 2 H), 2.12 (s, 3 H), 2.18 (s, 3 H), 2.56 (t, J = 7.2 Hz, 2 H), 3.73 (s, 3 H), 4.77 (d, J = 12.5 Hz, 1 H), 5.30 (d, J = 12.5 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.75 (dd, J = 8.2, 2.1 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.85 (d, J = 2.1 Hz, 1 H), 7.14 (d, J = 2.1 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 1 H), 7.63 (dd, J = 8.1, 2.1 Hz, 1 H) |
6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-71) |
1 H-NMR (500 MHz, DMSO-D6) δ 0.90 (s, 3 H), 1.19 (s, 3 H), 2.13 (s, 3 H), 2.19 (s, 3 H), 3.76 (s, 3 H), 3.88 (s, 3 H), 4.81 (d, J = 12.7 Hz, 1 H), 5.34 (d, J = 12.7 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 7.11 (t, J = 7.5 Hz, 1 H), 7.17 (d, J = 2.0 Hz, 1 H), 7.24 (d, J = 8.6 Hz, 1 H), 7.32 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 7.9 Hz, 1 H), 7.63-7.66 (m, 2 H), 7.93 (dd, J = 7.9, 2.0 Hz, 1 H) |
6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-72) |
1 H-NMR (400 MHz, DMSO-D6) δ 0.91 (s, 3 H), 1.19 (s, 3 H), 2.14 (s, 3 H), 2.19 (s, 3 H), 3.76 (s, 3 H), 4.81 (d, J = 12.5 Hz, 1 H), 5.33 (d, J = 12.5 Hz, 1 H), 5.41 (s, 1 H), 6.07 (s, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.83 (d, J = 8.2 Hz, 1 H), 6.97 (dd, J = 8.3, 2.2 Hz, 1 H), 7.11 (d, J = 2.2 Hz, 1 H), 7.18 (d, J = 2.2 Hz, 1 H), 7.34 (d, J = 8.3 Hz, 1 H), 7.34 (d, J = 8.3 Hz, 1 H), 7.63-7.68 (m, 2 H), 8.48 (dt, J = 8.1, 2.0 Hz, 1 H), 8.91 (dd, J = 4.8, 2.0 Hz, 1 H), 9.28 (dd, J = 2.0, 0.7 Hz, 1 H) |
6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-73) |
1 H-NMR (500 MHz, DMSO-D6) δ 0.91 (s, 3 H), 1.19 (s, 3 H), 2.13 (s, 3 H), 2.19 (s, 3 H), 3.75 (s, 3 H), 4.80 (d, J = 12.7 Hz, 1 H), 5.32 (d, J = 12.7 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.63 (d, J = 8.6 Hz, 1 H), 6.81 (dd, J = 3.4, 1.8 Hz, 1 H), 6.82 (d, J = 8.6 Hz, 1 H), 6.90 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03 (d, J = 2.2 Hz, 1 H), 7.17 (d, J = 2.1 Hz, 1 H), 7.32 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 8.2 Hz, 1 H), 7.57 (dd, J = 3.4, 0.8 Hz, 1 H), 7.64 (dd, J = 8.2, 2.1 Hz, 1 H), 8.11 (dd, J = 1.8, 0.8 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-74) |
1 H-NMR (400 MHz, DMSO-d3) δ 1.04 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.72 (s, 3 H), 3.83 (s, 3 H), 4.69 (d, J = 12.0 Hz, 1 H), 5.28 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.2, 2.2 Hz, 1 H), 7.01 (d, J = 2.2 Hz, 1 H), 7.09 (d, J = 9.0 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 2.7 Hz, 1 H), 7.54-7.58 (m, 1 H), 7.67-7.69 (m, 2 H), 7.82 (dd, J = 9.0, 2.7 Hz, 1 H), 8.09 (ddd, J = 7.7, 1.2, 0.7 Hz, 1 H) |
5-(2-메톡시-5-니트로페녹시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-75) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.70 (s, 3 H), 3.83 (s, 3 H), 4.69 (d, J = 11.9 Hz, 1 H), 5.28 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.85 (dd, J = 8.3, 2.3 Hz, 1 H), 7.05 (d, J = 2.3 Hz, 1 H), 7.09 (d, J = 9.1 Hz, 1 H), 7.21 (d, J = 8.3 Hz, 1 H), 7.34 (d, J = 2.7 Hz, 1 H), 7.66 (ddd, J = 8.1, 4.9, 1.0 Hz, 1 H), 7.82 (dd, J = 9.1, 2.7 Hz, 1 H), 8.46 (dt, J = 8.1, 1.9 Hz, 1 H), 8.90 (dd, J = 4.9, 1.9 Hz, 1 H), 9.25 (dd, J = 1.9, 1.0 Hz, 1 H) |
5-(2-메톡시-5-니트로페녹시메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-76) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.70 (s, 3 H), 3.83 (s, 3 H), 4.68 (d, J = 11.9 Hz, 1 H), 5.27 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H), 6.85 (dd, J = 8.2, 2.4 Hz, 1 H), 7.05 (d, J = 2.4 Hz, 1 H), 7.09 (d, J = 9.1 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 2.7 Hz, 1 H), 7.82 (dd, J = 9.1, 2.7 Hz, 1 H), 8.00 (d, J = 6.0 Hz, 2 H), 8.89 (d, J = 6.0 Hz, 2 H) |
6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-77) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 2.78 (s, 3 H), 3.71 (s, 3 H), 3.83 (s, 3 H), 4.69 (d, J = 12.3 Hz, 1 H), 5.28 (d, J = 12.3 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.79 (d, J = 8.3 Hz, 1 H), 6.84 (dd, J = 8.3, 2.2 Hz, 1 H), 7.04 (d, J = 2.2 Hz, 1 H), 7.09 (d, J = 9.0 Hz, 1 H), 7.21 (d, J = 8.3 Hz, 1 H), 7.33 (d, J = 2.8 Hz, 1 H), 7.47 (dd, J = 8.1, 4.9 Hz, 1 H), 7.82 (dd, J = 9.0, 2.8 Hz, 1 H), 8.42 (dd, J = 8.1, 1.8 Hz, 1 H), 8.71 (dd, J = 4.9, 1.8 Hz, 1 H) |
6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-78) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.71 (s, 3 H), 3.83 (s, 3 H), 3.87 (s, 3 H), 4.69 (d, J = 12.2 Hz, 1 H), 5.28 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.77 (dd, J = 7.9, 2.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.93 (d, J = 2.2 Hz, 1 H), 7.09 (d, J = 9.1 Hz, 1 H), 7.10 (d, J = 8.1 Hz, 1 H), 7.19 (d, J = 7.9 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 1 H), 7.33 (d, J = 2.6 Hz, 1 H), 7.64 (ddd, J = 8.1, 7.3, 1.7 Hz, 1 H), 7.82 (dd, J = 9.1, 2.6 Hz, 1 H), 7.90 (dd, J = 7.3, 1.7 Hz, 1 H) |
6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-79) |
1 H-NMR (400 MHz, DMSO-d6) δ1.05 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.69 (s, 3 H), 3.82 (s, 3 H), 4.67 (d, J = 11.9 Hz, 1 H), 5.27 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.79 (dd, J = 8.2, 2.2 Hz, 1 H), 6.80 (dd, J = 3.5, 1.8 Hz, 1 H), 6.97 (d, J = 2.2 Hz, 1 H), 7.09 (d, J = 9.2 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 2.7 Hz, 1 H), 7.55 (dd, J = 3.5, 0.9 Hz, 1 H), 7.82 (dd, J = 9.2, 2.7 Hz, 1 H), 8.10 (dd, J = 1.8, 0.9 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-80) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.91 (s, 3 H), 1.19 (s, 3 H), 2.14 (s, 3 H), 2.19 (s, 3 H), 3.77 (s, 3 H), 4.81 (d, J = 12.9 Hz, 1 H), 5.34 (d, J = 12.9 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.83 (d, J = 8.3 Hz, 1 H), 6.95 (dd, J = 8.2, 2.2 Hz, 1 H), 7.08 (d, J = 2.2 Hz, 1 H), 7.18 (d, J = 2.2 Hz, 1 H), 7.34 (d, J = 8.2 Hz, 1 H), 7.35 (d, J = 8.2 Hz, 1 H), 7.55-7.59 (m, 1 H), 7.64 (dd, J = 8.2, 2.2 Hz, 1 H), 7.68-7.69 (m, 2 H), 8.11 (d, J = 7.6 Hz, 1 H) |
5-(2-메톡시-5-니트로페녹시메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-81) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.69 (s, 3 H), 3.83 (s, 3 H), 4.68 (d, J = 11.9 Hz, 1 H), 5.27 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 2 H), 6.96 (d, J = 2.1 Hz, 1 H), 7.09 (d, J = 9.1 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 2.7 Hz, 1 H), 7.60 (dd, J = 5.1, 1.2 Hz, 1 H), 7.75 (dd, J = 5.1, 3.1 Hz, 1 H), 7.82 (dd, J = 9.1, 2.7 Hz, 1 H), 8.58 (dd, J = 3.1, 1.2 Hz, 1 H) |
6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-82) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.71 (s, 3 H), 3.83 (s, 3 H), 4.69 (d, J = 11.9 Hz, 1 H), 5.28 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.82 (dd, J = 8.2, 2.3 Hz, 1 H), 7.01 (d, J = 2.3 Hz, 1 H), 7.09 (d, J = 9.0 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 2.7 Hz, 1 H), 7.40-7.46 (m, 2 H), 7.75-7.81 (m, 1 H), 7.82 (dd, J = 9.0, 2.7 Hz, 1 H), 8.09 (t, J = 7.7 Hz, 1 H) |
6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-83) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.70 (s, 3 H), 3.83 (s, 3 H), 4.69 (d, J = 11.9 Hz, 1 H), 5.28 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.81 (dd, J = 8.1, 2.3 Hz, 1 H), 7.00 (d, J = 2.3 Hz, 1 H), 7.09 (d, J = 9.1 Hz, 1 H), 7.20 (d, J = 8.1 Hz, 1 H), 7.33 (d, J = 2.7 Hz, 1 H), 7.45 (t, J = 9.1 Hz, 2 H), 7.82 (dd, J = 9.1, 2.7 Hz, 1 H), 8.19 (dd, J = 9.1, 5.5 Hz, 2 H) |
6-[2-메톡시-4-(2-니트로벤조일옥시)페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-84) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.19 (s, 3 H), 2.15 (s, 3 H), 3.71 (s, 3 H), 3.82 (s, 3 H), 4.69 (d, J = 12.1 Hz, 1 H), 5.27 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.81 (dd, J = 8.2, 2.2 Hz, 1 H), 6.97 (d, J = 2.2 Hz, 1 H), 7.08 (d, J = 9.0 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 2.7 Hz, 1 H), 7.81 (dd, J = 9.0, 2.7 Hz, 1 H), 7.91 (td, J = 7.7, 1.6 Hz, 1 H), 7.96 (td, J = 7.7, 1.3 Hz, 1 H), 8.10 (dd, J = 7.7, 1.6 Hz, 1 H), 8.19 (dd, J = 7.7, 1.3 Hz, 1 H) |
6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-85) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.91 (s, 3 H), 1.19 (s, 3 H), 2.13 (s, 3 H), 2.19 (s, 3 H), 3.75 (s, 3 H), 4.80 (d, J = 12.7 Hz, 1 H), 5.33 (d, J = 12.7 Hz, 1 H), 5.41 (s, 1 H), 6.05 (s, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.3, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.17 (d, J = 2.1 Hz, 1 H), 7.32 (d, J = 8.3 Hz, 1 H), 7.34 (d, J = 8.1 Hz, 1 H), 7.62 (dd, J = 5.1, 1.3 Hz, 1 H), 7.64 (dd, J = 8.1, 2.1 Hz, 1 H), 7.75 (dd, J = 5.1, 2.9 Hz, 1 H), 8.61 (dd, J = 2.9, 1.3 Hz, 1 H) |
6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-86) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.91 (s, 3 H), 1.18 (s, 3 H), 2.13 (s, 3 H), 2.19 (s, 3 H), 3.74 (s, 3 H), 4.79 (d, J = 12.2 Hz, 1 H), 5.32 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 1 H), 6.87 (dd, J = 8.1, 2.4 Hz, 1 H), 6.94 (dd, J = 1.7, 0.7 Hz, 1 H), 6.99 (d, J = 2.4 Hz, 1 H), 7.17 (d, J = 2.3 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.64 (dd, J = 8.2, 2.3 Hz, 1 H), 7.92 (t, J = 1.7 Hz, 1 H), 8.64 (dd, J = 1.7, 0.7 Hz, 1 H) |
6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-87) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.91 (s, 3 H), 1.19 (s, 3 H), 2.14 (s, 3 H), 2.19 (s, 3 H), 2.80 (s, 3 H), 3.76 (s, 3 H), 4.81 (d, J = 12.7 Hz, 1 H), 5.34 (d, J = 12.7 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.64 (d, J = 8.3 Hz, 1 H), 6.83 (d, J = 8.3 Hz, 1 H), 6.95 (dd, J = 8.1, 2.3 Hz, 1 H), 7.10 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 2.1 Hz, 1 H), 7.34 (d, J = 8.1 Hz, 2 H), 7.47 (dd, J = 8.0, 4.9 Hz, 1 H), 7.64 (dd, J = 8.1, 2.1 Hz, 1 H), 8.45 (dd, J = 8.0, 1.7 Hz, 1 H), 8.72 (dd, J = 4.9, 1.7 Hz, 1 H) |
6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-88) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.90 (s, 3 H), 1.19 (s, 3 H), 2.13 (s, 3 H), 2.19 (s, 3 H), 2.38 (s, 3 H), 3.75 (s, 3 H), 4.81 (d, J = 12.5 Hz, 1 H), 5.33 (d, J = 12.5 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.63 (d, J = 8.1 Hz, 1 H), 6.70 (d, J = 1.7 Hz, 1 H), 6.81 (d, J = 8.1 Hz, 1 H), 6.89 (dd, J = 8.2, 2.4 Hz, 1 H), 7.01 (d, J = 2.4 Hz, 1 H), 7.17 (d, J = 2.3 Hz, 1 H), 7.31 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.64 (dd, J = 8.2, 2.3 Hz, 1 H), 7.95 (d, J = 1.7 Hz, 1 H) |
6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-89) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.91 (s, 3 H), 1.19 (s, 3 H), 2.13 (s, 3 H), 2.19 (s, 3 H), 3.75 (s, 3 H), 4.81 (d, J = 12.7 Hz, 1 H), 5.33 (d, J = 12.7 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.83 (d, J = 8.2 Hz, 1 H), 6.97 (dd, J = 8.2, 2.1 Hz, 1 H), 7.11 (d, J = 2.1 Hz, 1 H), 7.18 (d, J = 2.2 Hz, 1 H), 7.34 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 8.2 Hz, 1 H), 7.65 (dd, J = 8.2, 2.2 Hz, 1 H), 8.02 (d, J = 6.1 Hz, 2 H), 8.90 (d, J = 6.1 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-90) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.03 (s, 3 H), 2.08 (s, 3 H), 3.74 (s, 3 H), 3.98 (s, 3 H), 4.64 (d, J = 12.1 Hz, 1 H), 5.10 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 6.86 (dd, J = 8.1, 2.3 Hz, 1 H), 7.01 (d, J = 2.3 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.20 (dd, J = 7.6, 4.9 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 1 H), 8.41 (dd, J = 7.6, 2.0 Hz, 1 H), 8.48 (dd, J = 4.9, 2.0 Hz, 1 H) |
6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-91) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 2.78 (s, 3 H), 3.68 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.4, 3.3 Hz, 1 H), 4.07 (dd, J = 12.4, 6.9 Hz, 1 H), 4.26 (dd, J = 6.9, 3.3 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.38 (dd, J = 7.8, 1.2 Hz, 1 H), 6.52 (td, J = 7.8, 1.2 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.8, 1.2 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.75 (dd, J = 7.8, 1.2 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 7.00 (d, J = 2.3 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H), 7.45 (dd, J = 7.9, 4.8 Hz, 1 H), 8.43 (dd, J = 7.9, 1.8 Hz, 1 H), 8.70 (dd, J = 4.8, 1.8 Hz, 1 H) |
6-(4-벤조일옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-92) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.4, 3.4 Hz, 1 H), 4.07 (dd, J = 12.4, 6.4 Hz, 1 H), 4.26 (dd, J = 6.4, 3.4 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.3 Hz, 1 H), 6.75 (dd, J = 7.8, 1.3 Hz, 1 H), 6.85 (dd, J = 8.1, 2.2 Hz, 1 H), 6.97 (d, J = 2.2 Hz, 1 H), 7.16 (d, J = 8.1 Hz, 1 H), 7.61 (t, J = 7.5 Hz, 2 H), 7.75 (t, J = 7.5 Hz, 1 H), 8.13 (d, J = 7.5 Hz, 2 H) |
6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-93) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.06 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.85-3.88 (m, 1 H), 3.86 (s, 3 H), 4.05-4.09 (m, 1 H), 4.24-4.26 (m, 1 H), 5.40 (s, 1 H), 6.01 (s, 1 H), 6.38 (dd, J = 7.7, 1.2 Hz, 1 H), 6.52 (td, J = 7.7, 1.2 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.7, 1.2 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.73-6.75 (m, 1 H), 6.80 (dd, J = 8.0, 2.3 Hz, 1 H), 6.89 (d, J = 2.3 Hz, 1 H), 7.07-7.10 (m, 1 H), 7.15 (d, J = 8.0 Hz, 1 H), 7.22 (d, J = 7.9 Hz, 1 H), 7.63 (td, J = 7.9, 1.7 Hz, 1 H), 7.90 (dd, J = 7.9, 1.7 Hz, 1 H) |
6-[2-메톡시-4-(2-메틸벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-94) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.03 (s, 3 H), 1.22 (s, 3 H), 2.06 (s, 3 H), 2.59 (s, 3 H), 3.68 (s, 3 H), 3.72 (s, 3 H), 3.85-3.88 (m, 1 H), 4.05-4.07 (m, 1 H), 4.25-4.26 (m, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.39 (d, J = 7.8 Hz, 1 H), 6.52 (t, J = 7.8 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.70 (t, J = 7.8 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 7.8 Hz, 1 H), 6.85 (dd, J = 8.2, 2.2 Hz, 1 H), 6.96 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.37-7.42 (m, 2 H), 7.56 (t, J = 7.7 Hz, 1 H), 8.07 (d, J = 7.7 Hz, 1 H) |
6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-95) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.66 (s, 3 H), 3.72 (s, 3 H), 3.81-3.84 (m, 1 H), 4.02-4.05 (m, 1 H), 4.24-4.26 (m, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.36 (d, J = 7.7 Hz, 1 H), 6.52 (t, J = 7.7 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.69 (t, J = 7.7 Hz, 1 H), 6.73 (d, J = 8.3 Hz, 1 H), 6.73-6.75 (m, 1 H), 6.80 (dd, J = 8.2, 2.3 Hz, 1 H), 6.89 (d, J = 2.3 Hz, 1 H), 6.93 (dd, J = 1.7, 0.8 Hz, 1 H), 7.14 (d, J = 8.2 Hz, 1 H), 7.90 (t, J = 1.7 Hz, 1 H), 8.62 (dd, J = 1.7, 0.8 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-96) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.66 (s, 3 H), 3.72 (s, 3 H), 3.83-3.86 (m, 1 H), 4.05-4.08 (m, 1 H), 4.24-4.26 (m, 1 H), 5.40 (s, 1 H), 6.01 (s, 1 H), 6.36 (dd, J = 7.7, 1.3 Hz, 1 H), 6.52 (td, J = 7.7, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.7, 1.3 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.7, 1.3 Hz, 1 H), 6.82 (dd, J = 8.3, 2.1 Hz, 1 H), 6.92 (d, J = 2.1 Hz, 1 H), 7.15 (d, J = 8.3 Hz, 1 H), 7.14 (dd, J = 5.1, 1.4 Hz, 1 H), 7.74 (dd, J = 5.1, 2.9 Hz, 1 H), 8.59 (dd, J = 2.9, 1.4 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-97) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.2, 3.3 Hz, 1 H), 4.06-4.09 (m, 1 H), 4.25 (dd, J = 6.8, 3.3 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.38 (dd, J = 7.7, 1.4 Hz, 1 H), 6.52 (td, J = 7.7, 1.4 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.7, 1.4 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.74-6.76 (m, 1 H), 6.90 (dd, J = 8.3, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.17 (d, J = 8.3 Hz, 1 H), 7.65 (ddd, J = 7.9, 4.9, 0.9 Hz, 1 H), 8.46 (dt, J = 7.9, 2.0 Hz, 1 H), 8.90 (dd, J = 4.9, 2.0 Hz, 1 H), 9.26 (dd, J = 2.0, 0.9 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-98) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.91 (s, 3 H), 2.05 (s, 3 H), 3.74 (s, 3 H), 3.95 (dd, J = 13.1, 5.2 Hz, 1 H), 4.10 (dd, J = 13.1, 4.2 Hz, 1 H), 4.25 (br s, 1 H), 5.41 (s, 1 H), 6.04 (s, 1 H), 6.07 (dd, J = 12.1, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.90 (dd, J = 8.1, 2.4 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 7.27 (d, J = 8.1 Hz, 1 H), 7.54-7.58 (m, 1 H), 7.67-7.69 (m, 2 H), 8.10 (d, J = 7.3 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-99) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.68 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.1, 2.8 Hz, 1 H), 4.03-4.09 (m, 1 H), 4.24-4.26 (m, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.38 (d, J = 7.5 Hz, 1 H), 6.52 (t, J = 7.5 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.69 (t, J = 7.5 Hz, 1 H), 6.74 (d, J = 8.3 Hz, 1 H), 6.74 (d, J = 7.5 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 6.98 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.53-7.57 (m, 1 H), 7.66-7.68 (m, 2 H), 8.09 (d, J = 7.6 Hz, 1 H) |
6-(4-부틸릴옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-100) |
1 H-NMR (400 MHz, CDCl3) δ 1.04 (t, J = 7.3 Hz, 3 H), 1.25 (s, 3 H), 1.29 (s, 3 H), 1.79 (sept, J = 7.3 Hz, 2 H), 2.17 (s, 3 H), 2.53 (t, J = 7.3 Hz, 2 H), 3.66 (s, 3 H), 3.75 (s, 3 H), 3.87 (br s, 1 H), 4.01 (d, J = 12.3 Hz, 1 H), 4.14 (d, J = 12.3 Hz, 1 H), 4.34 (br s, 1 H), 5.46 (s, 1 H), 6.38 (dd, J = 7.8, 1.5 Hz, 1 H), 6.55-6.59 (m, 1 H), 6.56 (d, J = 8.1 Hz, 1 H), 6.59 (d, J = 2.2 Hz, 1 H), 6.67 (dd, J = 8.1, 2.2 Hz, 1 H), 6.69 (dd, J = 7.8, 1.5 Hz, 1 H), 6.77 (td, J = 7.8, 1.5 Hz, 1 H), 6.85 (d, J = 8.1 Hz, 1 H), 7.14 (d, J = 8.1 Hz, 1 H) |
6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-101) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.7, 3.3 Hz, 1 H), 4.07 (dd, J = 12.7, 6.5 Hz, 1 H), 4.25 (dd, J = 6.5, 3.3 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.38 (dd, J = 7.6, 1.2 Hz, 1 H), 6.52 (td, J = 7.6, 1.2 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.6, 1.2 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.6, 1.2 Hz, 1 H), 6.86 (dd, J = 8.1, 2.3 Hz, 1 H), 6.97 (d, J = 2.3 Hz, 1 H), 7.16 (d, J = 8.1 Hz, 1 H), 7.39-7.46 (m, 2 H), 7.75-7.80 (m, 1 H), 8.10 (td, J = 7.7, 1.8 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-102) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.85 (dd, J = 12.3, 3.5 Hz, 1 H), 4.07 (dd, J = 12.3, 7.0 Hz, 1 H), 4.25 (dd, J = 7.0, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.90 (dd, J = 8.1, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.18 (d, J = 8.1 Hz, 1 H), 8.00 (d, J = 6.1 Hz, 2 H), 8.88 (d, J = 6.1 Hz, 2 H) |
6-(4-이소프로필카르보닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-103) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.22 (d, J = 6.8 Hz, 6 H), 2.06 (s, 3 H), 2.78 (hept, J = 6.8 Hz, 1 H), 3.65 (s, 3 H), 3.71 (s, 3 H), 3.82 (dd, J = 12.4, 3.2 Hz, 1 H), 4.04 (dd, J = 12.4, 6.7 Hz, 1 H), 4.23 (dd, J = 6.7, 3.2 Hz, 1 H), 5.39 (s, 1 H), 6.01 (s, 1 H), 6.35 (dd, J = 7.8, 1.6 Hz, 1 H), 6.51 (td, J = 7.8, 1.6 Hz, 1 H), 6.60 (d, J = 8.3 Hz, 1 H), 6.67 (dd, J = 8.1, 2.1 Hz, 1 H), 6.68-6.72 (m, 1 H), 6.71 (d, J = 8.3 Hz, 1 H), 6.74 (dd, J = 7.8, 1.6 Hz, 1 H), 6.75 (d, J = 2.1 Hz, 1 H), 7.10 (d, J = 8.1 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-104) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.85 (dd, J = 12.2, 3.5 Hz, 1 H), 4.04-4.08 (m, 1 H), 4.24 (dd, J = 6.6, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.37 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.84 (dd, J = 8.1, 2.3 Hz, 1 H), 6.94 (d, J = 2.3 Hz, 1 H), 7.15 (d, J = 8.1 Hz, 1 H), 7.31 (dd, J = 5.0, 3.7 Hz, 1 H), 8.01 (dd, J = 3.7, 1.3 Hz, 1 H), 8.09 (dd, J = 5.0, 1.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-105) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.12 (s, 3 H), 1.20 (s, 3 H), 1.92 (s, 3 H), 2.05 (s, 3 H), 3.72 (s, 3 H), 3.95 (dd, J = 13.1, 4.6 Hz, 1 H), 4.10 (dd, J = 13.1, 4.6 Hz, 1 H), 4.24 (t, J = 4.6 Hz, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.08 (dd, J = 12.4, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.87-6.90 (m, 1 H), 6.92 (dd, J = 8.1, 2.3 Hz, 1 H), 7.08 (d, J = 2.3 Hz, 1 H), 7.27 (d, J = 8.1 Hz, 1 H), 7.66 (ddd, J = 8.0, 4.9, 0.9 Hz, 1 H), 8.47 (dt, J = 8.0, 2.0 Hz, 1 H), 8.90 (dd, J = 4.9, 2.0 Hz, 1 H), 9.27 (dd, J = 2.0, 0.9 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-106) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.90 (s, 3 H), 2.05 (s, 3 H), 3.71 (s, 3 H), 3.93 (dd, J = 13.1, 4.2 Hz, 1 H), 4.09 (dd, J = 13.1, 4.2 Hz, 1 H), 4.24 (t, J = 4.2 Hz, 1 H), 5.41 (s, 1 H), 6.04 (s, 1 H), 6.06 (dd, J = 12.7, 2.6 Hz, 1 H), 6.21 (td, J = 8.5, 2.6 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.80 (dd, J = 3.6, 1.7 Hz, 1 H), 6.84-6.90 (m, 2 H), 6.99 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.3 Hz, 1 H), 7.57 (dd, J = 3.6, 0.8 Hz, 1 H), 8.11 (dd, J = 1.7, 0.8 Hz, 1 H) |
6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-107) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.87 (dd, J = 12.4, 3.3 Hz, 1 H), 3.91 (s, 3 H), 4.07 (dd, J = 12.4, 6.6 Hz, 1 H), 4.26 (dd, J = 6.6, 3.3 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.70 (td, J = 7.8, 1.3 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.75 (dd, J = 7.8, 1.3 Hz, 1 H), 6.89 (dd, J = 8.1, 2.3 Hz, 1 H), 7.01 (d, J = 2.3 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H), 7.78 (t, J = 7.8 Hz, 1 H), 8.30 (dt, J = 7.8, 1.5 Hz, 1 H), 8.38 (dt, J = 7.8, 1.5 Hz, 1 H), 8.64 (t, J = 1.5 Hz, 1 H) |
6-[2-메톡시-4-(4-메틸벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-108) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 2.42 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.2, 3.5 Hz, 1 H), 4.07 (dd, J = 12.2, 6.3 Hz, 1 H), 4.25 (dd, J = 6.3, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.01 (s, 1 H), 6.38 (dd, J = 7.7, 1.3 Hz, 1 H), 6.52 (td, J = 7.7, 1.3 Hz, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.69 (td, J = 7.7, 1.3 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 6.74 (dd, J = 7.7, 1.3 Hz, 1 H), 6.84 (dd, J = 8.2, 2.2 Hz, 1 H), 6.94 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.41 (d, J = 8.4 Hz, 2 H), 8.02 (d, J = 8.4 Hz, 2 H) |
6-[2-메톡시-4-(4-메톡시벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-109) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.66 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.5, 3.5 Hz, 1 H), 3.87 (s, 3 H), 4.07 (dd, J = 12.5, 6.5 Hz, 1 H), 4.25 (dd, J = 6.5, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.01 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.82 (dd, J = 8.2, 2.4 Hz, 1 H), 6.92 (d, J = 2.4 Hz, 1 H), 7.12 (d, J = 9.0 Hz, 2 H), 7.14 (d, J = 8.2 Hz, 1 H), 8.08 (d, J = 9.0 Hz, 2 H) |
6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-110) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.2, 3.1 Hz, 1 H), 4.07 (dd, J = 12.2, 6.6 Hz, 1 H), 4.25 (dd, J = 6.6, 3.1 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.85 (dd, J = 8.0, 2.4 Hz, 1 H), 6.97 (d, J = 2.4 Hz, 1 H), 7.16 (d, J = 8.0 Hz, 1 H), 7.41-7.47 (m, 2 H), 8.18-8.23 (m, 2 H) |
6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-111) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 2.46 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 13.0, 3.4 Hz, 1 H), 4.07 (dd, J = 13.0, 6.9 Hz, 1 H), 4.25 (dd, J = 6.9, 3.4 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.83 (dd, J = 8.2, 2.2 Hz, 1 H), 6.94 (d, J = 2.2 Hz, 1 H), 7.16 (d, J = 8.2 Hz, 1 H), 7.31 (td, J = 7.8, 1.5 Hz, 1 H), 7.46 (dd, J = 7.8, 1.5 Hz, 1 H), 7.66 (td, J = 7.8, 1.5 Hz, 1 H), 8.17 (dd, J = 7.8, 1.5 Hz, 1 H) |
6-[4-(3-아세틸벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-112) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 2.67 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.3, 3.1 Hz, 1 H), 4.08 (dd, J = 12.3, 6.7 Hz, 1 H), 4.26 (dd, J = 6.7, 3.1 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.70 (td, J = 7.8, 1.3 Hz, 1 H), 6.75 (d, J = 8.1 Hz, 2 H), 6.89 (dd, J = 8.2, 2.3 Hz, 1 H), 7.00 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.77 (t, J = 7.8 Hz, 1 H), 8.31 (dt, J = 7.8, 1.5 Hz, 1 H), 8.36 (dt, J = 7.8, 1.5 Hz, 1 H), 8.61 (t, J = 1.5 Hz, 1 H) |
6-[4-(3-클로로티오펜-2-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-113) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 12.2, 3.4 Hz, 1 H), 4.06 (dd, J = 12.2, 6.6 Hz, 1 H), 4.24 (dd, J = 6.6, 3.4 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.37 (dd, J = 7.8, 1.4 Hz, 1 H), 6.52 (td, J = 7.8, 1.4 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.69 (td, J = 7.8, 1.4 Hz, 1 H), 6.73 (d, J = 8.3 Hz, 1 H), 6.75 (dd, J = 7.8, 1.4 Hz, 1 H), 6.84 (dd, J = 8.3, 2.2 Hz, 1 H), 6.96 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.3 Hz, 1 H), 7.35 (d, J = 5.2 Hz, 1 H), 8.14 (d, J = 5.2 Hz, 1 H) |
6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-114) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.07 (s, 3 H), 2.36 (s, 3 H), 3.66 (s, 3 H), 3.72 (s, 3 H), 3.87 (dd, J = 12.4, 3.5 Hz, 1 H), 4.06 (dd, J = 12.4, 6.9 Hz, 1 H), 4.24 (dd, J = 6.9, 3.5 Hz, 1 H), 5.39 (s, 1 H), 6.01 (s, 1 H), 6.37 (dd, J = 7.7, 1.4 Hz, 1 H), 6.51 (td, J = 7.7, 1.4 Hz, 1 H), 6.61 (d, J = 7.9 Hz, 1 H), 6.69 (d, J = 1.4 Hz, 1 H), 6.69 (td, J = 7.7, 1.4 Hz, 1 H), 6.73 (d, J = 7.9 Hz, 1 H), 6.74 (dd, J = 7.7, 1.4 Hz, 1 H), 6.81 (dd, J = 8.0, 2.2 Hz, 1 H), 6.92 (d, J = 2.2 Hz, 1 H), 7.14 (d, J = 8.0 Hz, 1 H), 7.94 (d, J = 1.4 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-115) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.86 (dd, J = 11.8, 3.5 Hz, 1 H), 4.07 (dd, J = 11.8, 6.8 Hz, 1 H), 4.24 (dd, J = 6.8, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.37 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 2 H), 6.85 (dd, J = 8.2, 2.2 Hz, 1 H), 6.95 (d, J = 2.2 Hz, 1 H), 7.16 (d, J = 8.2 Hz, 1 H), 8.86 (d, J = 2.0 Hz, 1 H), 9.27 (d, J = 2.0 Hz, 1 H) |
6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-116) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 2.60 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.85 (dd, J = 12.1, 3.4 Hz, 1 H), 4.07 (dd, J = 12.1, 6.4 Hz, 1 H), 4.25 (dd, J = 6.4, 3.4 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.37 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.69 (td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.87 (dd, J = 8.1, 2.3 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 7.16 (d, J = 8.1 Hz, 1 H), 7.50 (d, J = 8.2 Hz, 1 H), 8.33 (dd, J = 8.2, 2.4 Hz, 1 H), 9.12 (d, J = 2.4 Hz, 1 H) |
6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-117) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.22 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.72 (s, 3 H), 3.85 (dd, J = 12.7, 3.1 Hz, 1 H), 3.97 (s, 3 H), 4.07 (dd, J = 12.7, 6.8 Hz, 1 H), 4.25 (dd, J = 6.8, 3.1 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.37 (dd, J = 7.7, 1.3 Hz, 1 H), 6.52 (td, J = 7.7, 1.3 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (td, J = 7.7, 1.3 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.7, 1.3 Hz, 1 H), 6.82 (dd, J = 8.1, 2.2 Hz, 1 H), 6.93 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.1 Hz, 1 H), 7.19 (dd, J = 7.5, 4.9 Hz, 1 H), 8.39 (dd, J = 7.5, 2.1 Hz, 1 H), 8.47 (dd, J = 4.9, 2.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-118) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.90 (s, 3 H), 2.05 (s, 3 H), 3.71 (s, 3 H), 3.93 (dd, J = 13.2, 4.6 Hz, 1 H), 4.08 (dd, J = 13.2, 4.6 Hz, 1 H), 4.20-4.25 (m, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.06 (dd, J = 12.2, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.83 (dd, J = 8.1, 2.2 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.94 (dd, J = 1.7, 0.9 Hz, 1 H), 6.96 (d, J = 2.2 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 1 H), 7.91 (t, J = 1.7 Hz, 1 H), 8.63 (dd, J = 1.7, 0.9 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-119) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.12 (s, 3 H), 1.20 (s, 3 H), 1.91 (s, 3 H), 2.05 (s, 3 H), 3.72 (s, 3 H), 3.94 (dd, J = 13.1, 4.9 Hz, 1 H), 4.10 (dd, J = 13.1, 4.2 Hz, 1 H), 4.23-4.26 (m, 1 H), 5.41 (s, 1 H), 6.04 (s, 1 H), 6.07 (dd, J = 12.2, 2.4 Hz, 1 H), 6.21 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.92 (dd, J = 8.3, 2.2 Hz, 1 H), 7.08 (d, J = 2.2 Hz, 1 H), 7.27 (d, J = 8.3 Hz, 1 H), 8.01 (d, J = 6.1 Hz, 2 H), 8.89 (d, J = 6.1 Hz, 2 H) |
6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-120) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.91 (s, 3 H), 2.05 (s, 3 H), 3.73 (s, 3 H), 3.95 (dd, J = 13.4, 4.8 Hz, 1 H), 4.10 (dd, J = 13.4, 4.2 Hz, 1 H), 4.22-4.27 (m, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.07 (dd, J = 12.2, 2.6 Hz, 1 H), 6.21 (td, J = 8.5, 2.6 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.76 (d, J = 8.3 Hz, 1 H), 6.85-6.91 (m, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 7.03 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 8.2 Hz, 1 H), 7.40-7.47 (m, 2 H), 7.75-7.81 (m, 1 H), 8.11 (td, J = 7.8, 1.6 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-121) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.91 (s, 3 H), 2.05 (s, 3 H), 3.72 (s, 3 H), 3.94 (dd, J = 13.0, 5.0 Hz, 1 H), 4.09 (dd, J = 13.0, 4.2 Hz, 1 H), 4.22-4.26 (m, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.07 (dd, J = 12.2, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.87 (dd, J = 8.2, 2.3 Hz, 1 H), 7.00 (d, J = 2.3 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.31 (dd, J = 5.0, 3.7 Hz, 1 H), 8.02 (dd, J = 3.7, 1.3 Hz, 1 H), 8.10 (dd, J = 5.0, 1.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-122) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.92 (s, 3 H), 2.05 (s, 3 H), 2.80 (s, 3 H), 3.73 (s, 3 H), 3.95 (dd, J = 13.0, 5.0 Hz, 1 H), 4.10 (dd, J = 13.0, 4.4 Hz, 1 H), 4.24-4.26 (m, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.07 (dd, J = 11.9, 2.5 Hz, 1 H), 6.21 (td, J = 8.5, 2.5 Hz, 1 H), 6.63 (d, J = 8.1 Hz, 1 H), 6.76 (d, J = 8.1 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.91 (dd, J = 8.1, 2.3 Hz, 1 H), 7.06 (d, J = 2.3 Hz, 1 H), 7.26 (d, J = 8.1 Hz, 1 H), 7.46 (dd, J = 7.9, 5.0 Hz, 1 H), 8.44 (dd, J = 7.9, 1.8 Hz, 1 H), 8.71 (dd, J = 5.0, 1.8 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[4-(2-메틸티오벤조일옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-123) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.91 (s, 3 H), 2.05 (s, 3 H), 2.47 (s, 3 H), 3.72 (s, 3 H), 3.95 (dd, J = 13.3, 4.5 Hz, 1 H), 4.10 (dd, J = 13.3, 4.3 Hz, 1 H), 4.23-4.26 (m, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.08 (dd, J = 12.1, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.1, 2.1 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.99 (d, J = 2.1 Hz, 1 H), 7.25 (d, J = 8.1 Hz, 1 H), 7.32 (t, J = 8.0 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1 H), 7.67 (td, J = 8.0, 1.6 Hz, 1 H), 8.18 (dd, J = 8.0, 1.6 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[4-(3-메톡시카르보닐벤조일옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-124) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.92 (s, 3 H), 2.05 (s, 3 H), 3.73 (s, 3 H), 3.92 (s, 3 H), 3.95 (dd, J = 13.1, 4.9 Hz, 1 H), 4.10 (dd, J = 13.1, 4.3 Hz, 1 H), 4.23-4.25 (m, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.08 (dd, J = 12.1, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H), 6.63 (d, J = 8.1 Hz, 1 H), 6.77 (d, J = 8.1 Hz, 1 H), 6.87-6.90 (m, 1 H), 6.91 (dd, J = 8.2, 2.1 Hz, 1 H), 7.07 (d, J = 2.1 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 1 H), 7.79 (t, J = 7.8 Hz, 1 H), 8.31 (dt, J = 7.8, 1.5 Hz, 1 H), 8.39 (dt, J = 7.8, 1.5 Hz, 1 H), 8.65 (t, J = 1.5 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-125) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.20 (s, 3 H), 1.91 (s, 3 H), 2.05 (s, 3 H), 3.72 (s, 3 H), 3.95 (dd, J = 13.2, 4.3 Hz, 1 H), 3.97 (s, 3 H), 4.09 (dd, J = 13.2, 4.3 Hz, 1 H), 4.23 (t, J = 4.3 Hz, 1 H), 5.41 (s, 1 H), 6.02 (s, 1 H), 6.07 (dd, J = 12.2, 2.4 Hz, 1 H), 6.21 (td, J = 8.4, 2.4 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.85 (dd, J = 8.0, 2.2 Hz, 1 H), 6.87-6.90 (m, 1 H), 6.98 (d, J = 2.2 Hz, 1 H), 7.19 (dd, J = 7.6, 4.9 Hz, 1 H), 7.25 (d, J = 8.0 Hz, 1 H), 8.40 (dd, J = 7.6, 2.0 Hz, 1 H), 8.47 (dd, J = 4.9, 2.0 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-126) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.19 (s, 3 H), 1.91 (s, 3 H), 2.04 (s, 3 H), 2.38 (s, 3 H), 3.72 (s, 3 H), 3.94 (dd, J = 12.9, 4.3 Hz, 1 H), 4.10 (dd, J = 12.9, 4.3 Hz, 1 H), 4.24 (t, J = 4.3 Hz, 1 H), 5.41 (s, 1 H), 6.03 (s, 1 H), 6.06 (dd, J = 12.2, 2.5 Hz, 1 H), 6.20 (td, J = 8.5, 2.5 Hz, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.69 (d, J = 1.7 Hz, 1 H), 6.75 (d, J = 8.3 Hz, 1 H), 6.84 (dd, J = 8.2, 2.3 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.98 (d, J = 2.3 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.95 (d, J = 1.7 Hz, 1 H) |
6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-127) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.67 (s, 3 H), 4.99 (d, J = 12.7 Hz, 1 H), 5.22 (d, J = 12.7 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.3, 2.2 Hz, 1 H), 7.00 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.28 (d, J = 8.3 Hz, 2 H), 7.32 (dd, J = 4.9, 3.9 Hz, 1 H), 7.73 (d, J = 8.3 Hz, 2 H), 8.03 (dd, J = 3.9, 1.3 Hz, 1 H), 8.10 (dd, J = 4.9, 1.3 Hz, 1 H) |
6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-128) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 2.61 (s, 3 H), 3.68 (s, 3 H), 4.92 (d, J = 12.6 Hz, 1 H), 5.19 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.88 (dd, J = 8.3, 2.2 Hz, 1 H), 6.89 (d, J = 3.6 Hz, 1 H), 7.05 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.49 (d, J = 3.6 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 8.36 (dd, J = 8.0, 2.6 Hz, 1 H), 9.15 (d, J = 2.6 Hz, 1 H) |
6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-129) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.66 (s, 3 H), 4.98 (d, J = 12.7 Hz, 1 H), 5.21 (d, J = 12.7 Hz, 1 H), 5.46 (s, 1 H), 6.11 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.80 (dd, J = 8.3, 2.4 Hz, 1 H), 6.95 (dd, J = 1.8, 0.7 Hz, 1 H), 6.95 (d, J = 2.4 Hz, 1 H), 7.19 (d, J = 8.3 Hz, 1 H), 7.28 (d, J = 8.1 Hz, 2 H), 7.72 (d, J = 8.1 Hz, 2 H), 7.92 (t, J = 1.8 Hz, 1 H), 8.64 (dd, J = 1.8, 0.7 Hz, 1 H) |
6-(4-이소부틸릴옥시-2-메톡시페닐)-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-130) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.23 (s, 3 H), 1.24 (d, J = 7.0 Hz, 6 H), 2.08 (s, 3 H), 2.35 (s, 3 H), 2.81 (septet, J = 7.0 Hz, 1 H), 3.65 (s, 3 H), 4.96 (d, J = 12.8 Hz, 1 H), 5.20 (d, J = 12.8 Hz, 1 H), 5.45 (s, 1 H), 6.09 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.67 (dd, J = 8.2, 2.2 Hz, 1 H), 6.77 (d, J = 8.1 Hz, 1 H), 6.80 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 2 H), 7.71 (d, J = 8.2 Hz, 2 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-131) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.69 (s, 3 H), 5.00 (d, J = 12.7 Hz, 1 H), 5.23 (d, J = 12.7 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 7.03 (d, J = 2.3 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.28 (d, J = 7.9 Hz, 2 H), 7.55-7.59 (m, 1 H), 7.68-7.69 (m, 2 H), 7.73 (d, J = 7.9 Hz, 2 H), 8.11 (d, J = 7.3 Hz, 1 H) |
6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-132) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.68 (s, 3 H), 3.88 (s, 3 H), 5.00 (d, J = 12.8 Hz, 1 H), 5.23 (d, J = 12.8 Hz, 1 H), 5.46 (s, 1 H), 6.11 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.1 Hz, 1 H), 6.94 (d, J = 2.2 Hz, 1 H), 7.08-7.12 (m, 1 H), 7.20 (d, J = 8.1 Hz, 1 H), 7.24 (d, J = 7.8 Hz, 1 H), 7.28 (d, J = 7.9 Hz, 2 H), 7.62-7.67 (m, 1 H), 7.73 (d, J = 7.9 Hz, 2 H), 7.92 (dd, J = 7.8, 1.7 Hz, 1 H) |
5-(4-메틸벤조일옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-133) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.67 (s, 3 H), 5.00 (d, J = 12.8 Hz, 1 H), 5.23 (d, J = 12.8 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.69 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.1, 2.3 Hz, 1 H), 7.07 (d, J = 2.3 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 1 H), 7.28 (d, J = 8.1 Hz, 2 H), 7.67 (ddd, J = 7.9, 4.9, 0.8 Hz, 1 H), 7.73 (d, J = 8.1 Hz, 2 H), 8.47-8.49 (m, 1 H), 8.91 (dd, J = 4.9, 1.8 Hz, 1 H), 9.28 (dd, J = 2.3, 0.8 Hz, 1 H) |
6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-134) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.66 (s, 3 H), 4.99 (d, J = 12.8 Hz, 1 H), 5.22 (d, J = 12.8 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 7.8 Hz, 1 H), 6.80 (d, J = 7.8 Hz, 1 H), 6.81 (dd, J = 3.5, 1.7 Hz, 1 H), 6.83 (dd, J = 8.2, 2.4 Hz, 1 H), 6.99 (d, J = 2.4 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.28 (d, J = 7.9 Hz, 2 H), 7.57 (dd, J = 3.5, 0.8 Hz, 1 H), 7.72 (d, J = 7.9 Hz, 2 H), 8.11 (dd, J = 1.7, 0.8 Hz, 1 H) |
6-(4-부틸릴옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-135) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.98 (t, J = 7.3 Hz, 3 H), 1.14 (s, 3 H), 1.21 (s, 3 H), 1.67 (sextet, J = 7.3 Hz, 2 H), 2.08 (s, 3 H), 2.46 (s, 3 H), 2.56 (t, J = 7.3 Hz, 2 H), 3.65 (s, 3 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.16 (d, J = 12.7 Hz, 1 H), 5.44 (s, 1 H), 6.09 (s, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.68 (dd, J = 8.2, 2.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 2.2 Hz, 1 H), 6.88 (dd, J = 3.7, 1.1 Hz, 1 H), 7.13 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H) |
6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-136) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 3.89 (s, 3 H), 4.93 (d, J = 12.6 Hz, 1 H), 5.19 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.10 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H), 6.81 (dd, J = 8.0, 2.1 Hz, 1 H), 6.89 (dd, J = 3.7, 1.0 Hz, 1 H), 6.95 (d, J = 2.1 Hz, 1 H), 7.09-7.12 (m, 1 H), 7.18 (d, J = 8.0 Hz, 1 H), 7.24 (d, J = 8.1 Hz, 1 H), 7.48 (d, J = 3.7 Hz, 1 H), 7.62-7.67 (m, 1 H), 7.93 (dd, J = 7.7, 1.8 Hz, 1 H) |
6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-137) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 3.7, 0.9 Hz, 1 H), 6.90 (dd, J = 8.1, 2.1 Hz, 1 H), 7.08 (d, J = 2.1 Hz, 1 H), 7.21 (d, J = 8.1 Hz, 1 H), 7.49 (d, J = 3.7 Hz, 1 H), 7.67 (ddd, J = 8.0, 4.9, 0.9 Hz, 1 H), 8.49 (dt, J = 8.0, 2.0 Hz, 1 H), 8.91 (dd, J = 4.9, 2.0 Hz, 1 H), 9.28 (dd, J = 2.0, 0.9 Hz, 1 H) |
6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-138) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.92 (d, J = 12.8 Hz, 1 H), 5.18 (d, J = 12.8 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 3.7 Hz, 1 H), 6.84 (dd, J = 8.2, 2.3 Hz, 1 H), 6.88 (dd, J = 3.7, 1.4 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.48 (d, J = 3.7 Hz, 1 H), 7.58 (dd, J = 3.7, 0.8 Hz, 1 H), 8.12 (dd, J = 1.4, 0.8 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-139) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.69 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 7.04 (d, J = 2.3 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.48 (d, J = 3.6 Hz, 1 H), 7.55-7.59 (m, 1 H), 7.68-7.69 (m, 2 H), 8.10-8.13 (m, 1 H) |
6-[4-(3-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-140) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.5 Hz, 1 H), 5.19 (d, J = 12.5 Hz, 1 H), 5.45 (s, 1 H), 6.10 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 4.0 Hz, 1 H), 7.06 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 4.0 Hz, 1 H), 7.67 (t, J = 7.8 Hz, 1 H), 7.85 (ddd, J = 7.8, 1.9, 1.1 Hz, 1 H), 8.10 (ddd, J = 7.8, 1.9, 1.1 Hz, 1 H), 8.13 (t, J = 1.9 Hz, 1 H) |
6-[4-(4-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-141) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.92 (d, J = 12.8 Hz, 1 H), 5.19 (d, J = 12.8 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.79 (d, J = 8.3 Hz, 1 H), 6.87 (dd, J = 8.1, 2.2 Hz, 1 H), 6.88 (d, J = 3.7 Hz, 1 H), 7.03 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.1 Hz, 1 H), 7.48 (d, J = 3.7 Hz, 1 H), 7.70 (d, J = 8.8 Hz, 2 H), 8.15 (d, J = 8.8 Hz, 2 H) |
6-(4-벤조일옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-142) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.93 (d, J = 12.6 Hz, 1 H), 5.20 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.86 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.8 Hz, 1 H), 7.63 (dd, J = 8.2, 7.5 Hz, 2 H), 7.76 (tt, J = 7.5, 1.4 Hz, 1 H), 8.15 (dd, J = 8.2, 1.4 Hz, 2 H) |
6-[2-메톡시-4-(2-메틸벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-143) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 2.61 (s, 3 H), 3.68 (s, 3 H), 4.94 (d, J = 12.7 Hz, 1 H), 5.20 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.68 (d, J = 8.1 Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H), 6.86 (dd, J = 8.1, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.1 Hz, 1 H), 7.40-7.43 (m, 1 H), 7.42 (d, J = 7.7 Hz, 1 H), 7.49 (d, J = 3.8 Hz, 1 H), 7.58 (td, J = 7.7, 1.2 Hz, 1 H), 8.10 (dd, J = 7.7, 1.2 Hz, 1 H) |
6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-144) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.20 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.87 (dd, J = 8.2, 2.3 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.03 (d, J = 2.3 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.41-7.46 (m, 2 H), 7.49 (d, J = 3.8 Hz, 1 H), 7.77-7.82 (m, 1 H), 8.12 (td, J = 7.7, 1.7 Hz, 1 H) |
6-[2-메톡시-4-(4-메톡시벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-145) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 3.88 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.10 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.83 (dd, J = 8.1, 2.2 Hz, 1 H), 6.89 (dd, J = 3.7, 1.2 Hz, 1 H), 6.98 (d, J = 2.2 Hz, 1 H), 7.14 (d, J = 8.9 Hz, 2 H), 7.18 (d, J = 8.1 Hz, 1 H), 7.49 (d, J = 3.7 Hz, 1 H), 8.10 (d, J = 8.9 Hz, 2 H) |
6-[2-메톡시-4-(피리미딘-5-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-146) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.92 (d, J = 12.6 Hz, 1 H), 5.19 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.89 (d, J = 3.6 Hz, 1 H), 6.93 (dd, J = 8.2, 2.3 Hz, 1 H), 7.10 (d, J = 2.3 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.6 Hz, 1 H), 9.44 (s, 2 H), 9.51 (s, 1 H) |
6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-147) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.92 (d, J = 13.2 Hz, 1 H), 5.19 (d, J = 13.2 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.83 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 6.99 (d, J = 2.2 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.8 Hz, 1 H), 7.63 (dd, J = 5.1, 1.3 Hz, 1 H), 7.76 (dd, J = 5.1, 2.9 Hz, 1 H), 8.62 (dd, J = 2.9, 1.3 Hz, 1 H) |
6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-148) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.91 (d, J = 12.5 Hz, 1 H), 5.18 (d, J = 12.5 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H), 6.81 (dd, J = 8.2, 2.3 Hz, 1 H), 6.89 (d, J = 3.7 Hz, 1 H), 6.95 (dd, J = 1.7, 0.7 Hz, 1 H), 6.96 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.48 (d, J = 3.7 Hz, 1 H), 7.93 (t, J = 1.7 Hz, 1 H), 8.65 (dd, J = 1.7, 0.7 Hz, 1 H) |
6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-149) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 3.93 (s, 3 H), 4.93 (d, J = 12.6 Hz, 1 H), 5.20 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.89 (dd, J = 8.2, 2.3 Hz, 1 H), 6.89 (d, J = 3.6 Hz, 1 H), 7.07 (d, J = 2.3 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.6 Hz, 1 H), 7.80 (td, J = 7.8, 0.5 Hz, 1 H), 8.31 (ddd, J = 7.8, 1.7, 1.2 Hz, 1 H), 8.40 (ddd, J = 7.8, 1.7, 1.2 Hz, 1 H), 8.66 (td, J = 1.7, 0.5 Hz, 1 H) |
6-[4-(3-아세틸벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-150) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 2.69 (s, 3 H), 3.68 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.20 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.06 (d, J = 2.2 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.8 Hz, 1 H), 7.79 (t, J = 7.8 Hz, 1 H), 8.33 (dt, J = 7.8, 1.5 Hz, 1 H), 8.39 (dt, J = 7.8, 1.5 Hz, 1 H), 8.63 (t, J = 1.5 Hz, 1 H) |
6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-151) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.46 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.94 (d, J = 12.6 Hz, 1 H), 5.20 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.3, 2.3 Hz, 1 H), 6.89 (d, J = 3.5 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.49 (d, J = 3.5 Hz, 1 H), 7.68 (ddd, J = 8.4, 7.6, 1.5 Hz, 1 H), 8.20 (dd, J = 7.6, 1.5 Hz, 1 H) |
6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-152) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.92 (d, J = 12.8 Hz, 1 H), 5.19 (d, J = 12.8 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.7 Hz, 1 H), 7.00 (d, J = 2.2 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.32 (dd, J = 4.9, 3.8 Hz, 1 H), 7.48 (d, J = 3.7 Hz, 1 H), 8.04 (dd, J = 3.8, 1.3 Hz, 1 H), 8.10 (dd, J = 4.9, 1.3 Hz, 1 H) |
6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-153) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 2.81 (s, 3 H), 3.69 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.20 (d, J = 12.7 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.07 (d, J = 2.2 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.47-7.49 (m, 2 H), 8.46 (dd, J = 7.9, 1.8 Hz, 1 H), 8.72 (dd, J = 4.9, 1.8 Hz, 1 H) |
6-[4-(3-클로로티오펜-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-154) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.92 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.79 (d, J = 8.3 Hz, 1 H), 6.85 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.6 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.37 (d, J = 5.4 Hz, 1 H), 7.49 (d, J = 3.6 Hz, 1 H), 8.16 (d, J = 5.4 Hz, 1 H) |
6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-155) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.5 Hz, 1 H), 5.19 (d, J = 12.5 Hz, 1 H), 5.45 (s, 1 H), 6.10 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.01 (d, J = 2.2 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.48 (d, J = 3.8 Hz, 1 H), 8.88 (d, J = 2.0 Hz, 1 H), 9.28 (d, J = 2.0 Hz, 1 H) |
6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-156) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 4.92 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.80 (d, J = 8.1 Hz, 1 H), 6.89 (d, J = 3.6 Hz, 1 H), 6.90 (dd, J = 8.2, 2.2 Hz, 1 H), 7.08 (d, J = 2.2 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.6 Hz, 1 H), 8.03 (d, J = 5.9 Hz, 2 H), 8.90 (d, J = 5.9 Hz, 2 H) |
5-(4-메톡시벤조일옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-157) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.16 (s, 3 H), 1.24 (s, 3 H), 2.10 (s, 3 H), 3.67 (s, 3 H), 3.81 (s, 3 H), 4.98 (d, J = 12.9 Hz, 1 H), 5.21 (d, J = 12.9 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.2, 2.2 Hz, 1 H), 7.00 (dt, J = 8.9, 2.2 Hz, 2 H), 7.07 (d, J = 2.2 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.67 (ddd, J = 8.0, 4.9, 0.8 Hz, 1 H), 7.79 (dt, J = 8.9, 2.2 Hz, 2 H), 8.48 (dt, J = 8.0, 2.0 Hz, 1 H), 8.91 (dd, J = 4.9, 2.0 Hz, 1 H), 9.28 (dd, J = 2.0, 0.8 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(4-메톡시벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-158) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.24 (s, 3 H), 2.10 (s, 3 H), 3.69 (s, 3 H), 3.81 (s, 3 H), 4.98 (d, J = 12.9 Hz, 1 H), 5.21 (d, J = 12.9 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.88 (dd, J = 8.3, 2.2 Hz, 1 H), 6.99 (dt, J = 8.9, 2.1 Hz, 2 H), 7.03 (d, J = 2.2 Hz, 1 H), 7.23 (d, J = 8.3 Hz, 1 H), 7.55-7.59 (m, 1 H), 7.68-7.69 (m, 2 H), 7.78 (dt, J = 8.9, 2.1 Hz, 2 H), 8.10-8.12 (m, 1 H) |
6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(4-메톡시벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-159) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.23 (s, 3 H), 2.09 (s, 3 H), 3.66 (s, 3 H), 3.81 (s, 3 H), 4.97 (d, J = 12.9 Hz, 1 H), 5.20 (d, J = 12.9 Hz, 1 H), 5.46 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.81 (dd, J = 3.6, 1.7 Hz, 1 H), 6.83 (dd, J = 8.1, 2.3 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 6.99 (dt, J = 9.1, 2.1 Hz, 2 H), 7.20 (d, J = 8.1 Hz, 1 H), 7.57 (dd, J = 3.6, 0.9 Hz, 1 H), 7.78 (dt, J = 9.1, 2.1 Hz, 2 H), 8.12 (dd, J = 1.7, 0.9 Hz, 1 H) |
5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-160) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.14 (s.3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 3.68 (s, 3 H), 4.99 (d, J = 12.8 Hz, 1 H), 5.23 (d, J = 12.8 Hz, 1 H), 5.47 (s, 1 H), 6.13 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.91 (dd, J = 8.2, 2.3 Hz, 1 H), 7.08 (d, J = 2.3 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 4.1 Hz, 1 H), 7.50 (d, J = 4.1 Hz, 1 H), 7.67 (dd, J = 7.9, 4.7 Hz, 1 H), 8.49 (dt, J = 7.9, 2.0 Hz, 1 H), 8.91 (dd, J = 4.7, 2.0 Hz, 1 H), 9.28 (d, J = 2.0 Hz, 1 H) |
5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-161) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.10 (s, 3 H), 3.69 (s, 3 H), 4.99 (d, J = 12.7 Hz, 1 H), 5.23 (d, J = 12.9 Hz, 1 H), 5.47 (s, 1 H), 6.14 (s, 1 H), 6.68 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 7.04 (d, J = 2.2 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H), 7.34 (d, J = 4.2 Hz, 1 H), 7.50 (d, J = 4.2 Hz, 1 H), 7.55-7.59 (m, 1 H), 7.68-7.70 (m, 2 H), 8.11-13 (m, 1 H) |
5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-162) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.13 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 3.67 (s, 3 H), 4.98 (d, J = 12.6 Hz, 1 H), 5.22 (d, J = 12.6 Hz, 1 H), 5.46 (s, 1 H), 6.13 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.79 (d, J = 8.3 Hz, 1 H), 6.82 (dd, J = 3.5, 1.7 Hz, 1 H), 6.85 (dd, J = 8.3, 2.2 Hz, 1 H), 7.00 (d, J = 2.2 Hz, 1 H), 7.19 (d, J = 8.3 Hz, 1 H), 7.33 (d, J = 4.0 Hz, 1 H), 7.50 (d, J = 4.0 Hz, 1 H), 7.58 (dd, J = 3.5, 0.8 Hz, 1 H), 8.12 (dd, J = 1.7, 0.8 Hz, 1 H) |
6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(3-플루오르벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-163) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.24 (s, 3 H), 2.11 (s, 3 H), 3.69 (s, 3 H), 5.08 (d, J = 12.9 Hz, 1 H), 5.29 (d, J = 12.9 Hz, 1 H), 5.49 (s, 1 H), 6.15 (s, 1 H), 6.69 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.2, 2.4 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.48-7.59 (m, 4 H), 7.65-7.70 (m, 3 H), 8.10-8.13 (m, 1 H) |
6-(4-이소프로필카르보닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-164) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 1.25 (d, J = 6.9 Hz, 6 H), 2.08 (s, 3 H), 2.47 (s, 3 H), 2.81 (heptet, J = 6.9 Hz, 1 H), 3.66 (s, 3 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.17 (d, J = 12.7 Hz, 1 H), 5.44 (s, 1 H), 6.10 (s, 1 H), 6.66 (d, J = 8.3 Hz, 1 H), 6.68 (dd, J = 8.2, 2.2 Hz, 1 H), 6.76 (d, J = 8.3 Hz, 1 H), 6.81 (d, J = 2.2 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 7.14 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 3.6 Hz, 1 H) |
6-[4-(2-아세톡시벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-165) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.27 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.79 (dd, J = 8.2, 1.8 Hz, 1 H), 6.88 (d, J = 3.7 Hz, 1 H), 6.95 (d, J = 1.8 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.34 (dd, J = 7.8, 1.3 Hz, 1 H), 7.48 (d, J = 3.7 Hz, 1 H), 7.51 (td, J = 7.8, 1.3 Hz, 1 H), 7.79 (td, J = 7.8, 1.3 Hz, 1 H), 8.18 (dd, J = 7.8, 1.3 Hz, 1 H) |
6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-166) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.68 (s, 3 H), 3.99 (s, 3 H), 4.92 (d, J = 12.6 Hz, 1 H), 5.19 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.83 (dd, J = 8.3, 2.2 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 6.98 (d, J = 2.2 Hz, 1 H), 7.19 (d, J = 8.3 Hz, 1 H), 7.21 (dd, J = 7.6, 4.9 Hz, 1 H), 7.49 (d, J = 3.8 Hz, 1 H), 8.41 (dd, J = 7.6, 2.0 Hz, 1 H), 8.48 (dd, J = 4.9, 2.0 Hz, 1 H) |
6-[2-메톡시-4-(3-메틸벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-167) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.43 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.10 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.80 (d, J = 8.1 Hz, 1 H), 6.85 (dd, J = 8.2, 2.1 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.01 (d, J = 2.1 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.49 (d, J = 3.8 Hz, 1 H), 7.51 (t, J = 7.6 Hz, 1 H), 7.57 (d, J = 7.6 Hz, 1 H), 7.95 (d, J = 7.6 Hz, 1 H), 7.97 (s, 1 H) |
6-[2-메톡시-4-(4-메틸벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-168) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.43 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.5 Hz, 1 H), 5.19 (d, J = 12.5 Hz, 1 H), 5.45 (s, 1 H), 6.10 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.2, 2.4 Hz, 1 H), 6.89 (d, J = 3.7 Hz, 1 H), 7.00 (d, J = 2.4 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.43 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 3.7 Hz, 1 H), 8.04 (d, J = 8.1 Hz, 2 H) |
6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-169) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H), 6.86 (dd, J = 8.2, 2.3 Hz, 1 H), 6.89 (d, J = 3.8 Hz, 1 H), 7.03 (d, J = 2.3 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.44-7.49 (m, 2 H), 7.49 (d, J = 3.8 Hz, 1 H), 8.20-8.24 (m, 2 H) |
6-[2-메톡시-4-(2-니트로벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-170) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.22 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.69 (s, 3 H), 4.92 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.2, 2.2 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 6.99 (d, J = 2.2 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.48 (d, J = 3.6 Hz, 1 H), 7.92 (td, J = 7.6, 1.4 Hz, 1 H), 7.97 (td, J = 7.6, 1.4 Hz, 1 H), 8.13 (dd, J = 7.6, 1.4 Hz, 1 H), 8.20 (dd, J = 7.6, 1.4 Hz, 1 H) |
6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-171) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.39 (s, 3 H), 2.47 (s, 3 H), 3.67 (s, 3 H), 4.93 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.70 (d, J = 1.7 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.82 (dd, J = 8.3, 2.3 Hz, 1 H), 6.88 (d, J = 3.8 Hz, 1 H), 6.98 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 8.3 Hz, 1 H), 7.48 (d, J = 3.8 Hz, 1 H), 7.96 (d, J = 1.7 Hz, 1 H) |
6-(4-벤조일옥시-2-메톡시페닐)-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-172) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.24 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.67 (s, 3 H), 5.00 (d, J = 12.8 Hz, 1 H), 5.23 (d, J = 12.8 Hz, 1 H), 5.46 (s, 1 H), 6.11 (s, 1 H), 6.69 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.86 (dd, J = 8.2, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.28 (d, J = 8.1 Hz, 2 H), 7.62 (t, J = 7.8 Hz, 2 H), 7.73 (d, J = 8.1 Hz, 2 H), 7.75-7.78 (m, 1 H), 8.14-8.16 (m, 2 H) |
6-[2-메톡시-4-(2-메틸벤조일옥시)페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-173) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.24 (s, 3 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 2.61 (s, 3 H), 3.68 (s, 3 H), 5.01 (d, J = 12.9 Hz, 1 H), 5.24 (d, J = 12.9 Hz, 1 H), 5.46 (s, 1 H), 6.12 (s, 1 H), 6.69 (d, J = 8.1 Hz, 1 H), 6.81 (d, J = 8.1 Hz, 1 H), 6.86 (dd, J = 8.1, 2.2 Hz, 1 H), 7.02 (d, J = 2.2 Hz, 1 H), 7.21 (d, J = 8.1 Hz, 1 H), 7.28 (d, J = 8.2 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 1 H), 7.42 (d, J = 7.4 Hz, 1 H), 7.56-7.60 (m, 1 H), 7.73 (d, J = 8.2 Hz, 2 H), 8.09 (d, J = 7.4 Hz, 1 H) |
6-(4-시클로헥실카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-174) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 1.17-1.72 (m, 10 H), 1.99-2.01 (m, 1 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.71 (s, 3 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.03 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.70 (dd, J = 8.3, 2.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.82 (d, J = 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.17 (d, J = 8.3 Hz, 1 H) |
6-(4-아크릴로일옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-175) |
1 H-NMR (500 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.75 (s, 3 H), 4.75 (d, J = 11.9 Hz, 1 H), 5.11 (d, J = 11.9 Hz, 1 H), 5.45 (s, 1 H), 6.03 (d, J = 10.4 Hz, 1 H), 6.19 (dd, J = 11.0, 2.4 Hz, 1 H), 6.34 (dd, J = 17.7, 10.4 Hz, 1 H), 6.42 (td, J = 8.3, 2.4 Hz, 1 H), 6.58 (d, J = 8.4 Hz, 1 H), 6.62 (d, J = 17.7 Hz, 1 H), 6.75 (d, J = 2.1 Hz, 1 H), 6.78 (dd, J = 8.2, 2.1 Hz, 1 H), 6.91 (d, J = 8.4 Hz, 1 H), 6.92-6.95 (m, 1 H), 7.26 (d, J = 8.2 Hz, 1 H) |
(실시예 2)
6-(5-아세톡시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 2)
5-(5-플루오르-2-메틸페녹시메틸)-6-(5-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-2, 62.5 mg, 0.14 mmol), 트리에틸아민(154 ㎕, 1.11 mmol)를 무수 디클로로메탄(1 mL)에 용해하고, 무수 초산(52 ㎕, 0.55 mmol)를 가하여, 실온에서 1.5시간 교반했다. 반응액에 클로로포름(10 mL)을 가하여, 물 (10 mL) 및 포화 식염수(300 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (56.6 mg)를 무색 아몰퍼스로서 얻었다. (수율 83%)
1 H-NMR (400 MHz, CDCl3) δ 1.15 (s, 3 H), 1.22 (s, 3 H), 2.07 (s, 3 H), 2.15 (s, 3 H), 2.25 (s, 3 H), 3.74 (s, 3 H), 4.01 (br s, 1 H), 4.75 (d, J = 12.0 Hz, 1 H), 5.10 (d, J = 12.0 Hz, 1 H), 5.46 (s, 1 H), 6.22 (dd, J = 11.2, 2.4 Hz, 1 H), 6.43 (td, J = 8.3, 2.4 Hz, 1 H), 6.58 (d, J = 8.1 Hz, 1 H), 6.90-6.96 (m, 3 H), 6.99 (d, J = 2.9 Hz, 1 H), 7.03 (dd, J = 8.8, 2.9 Hz, 1 H) |
(실시예 3)
6-(4-아미노아세톡시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린·1 염산염(화합물 3-1)
6-(4-t-부톡시카르보닐아미노아세톡시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 1-2, 20.1 mg, 0.034 mmol)를 1, 4-디옥산(0.5 mL)에 용해하고, 4N 염화수소/1, 4-디옥산 용액(34 ㎕)을 가하여, 실온에서 밤새 교반했다. 반응액을 감압하 농축함으로써 표기 화합물 (17.5 mg)를 무색 고체로서 얻었다. (수율 98%)
1 H-NMR (400 MHz, DMSO-d6) δ 1.09 (s, 3 H), 1.18 (s, 3 H), 2.01 (s, 3 H), 2.09 (s, 3 H), 3.73 (s, 3 H), 4.09-4.10 (m, 2 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.08 (d, J = 12.1 Hz, 1 H), 5.47 (s, 1 H), 6.35 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.75-6.87 (m, 1 H), 6.80 (dd, J = 8.3, 2.2 Hz, 1 H), 6.86 (d, J = 8.1 Hz, 1 H), 6.91 (d, J = 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.25 (d, J = 8.3 Hz, 1 H), 8.49 (br s, 3 H) |
이하, 화합물 1-37을 사용하고, 화합물 3-1의 제조 방법에 준하여, 화합물 3-2를 얻었다.
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피페리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린ㆍ1염산염(화합물 3-2) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 1.87-1.95 (m, 2 H), 2.01 (s, 3 H), 2.10 (s, 3 H), 2.10-2.17 (m, 2 H), 2.96-3.01 (m, 3 H), 3.29-3.32 (m, 2 H), 3.74 (s, 3 H), 4.66 (d, J = 12.4 Hz, 1 H), 5.11 (d, J = 12.4 Hz, 1 H), 5.57 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.54 (td, J = 8.4, 2.4 Hz, 1 H), 6.79 (dd, J = 8.2, 2.2 Hz, 1 H), 6.92 (d, J = 2.2 Hz, 1 H), 6.93-7.00 (m, 2 H), 6.96 (br s, 1 H), 7.03-7.06 (m, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 8.88 (br s, 1 H), 9.08 (br s, 1 H) |
(실시예 4)
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-메틸설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-1)
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1, 61.0 mg, 0.141 mmol)를 염화메틸렌(2 mL)에 용해하고, 염화 메탄술포닐(26 ㎕, 0.34 mmol), 트리에틸아민(92 ㎕, 0.66 mmol)를 가하여, 실온에서 밤새 교반하였다. 반응액을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (58.0 mg)를 담복숭아색 고체로서 얻었다. (수율 82%)
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.15 (s, 3 H), 2.00 (s, 3 H), 2.07 (s, 3 H), 3.37 (s, 3 H), 3.75 (s, 3 H), 4.60 (d, J = 12.2 Hz, 1 H), 5.06 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.36 (dd, J = 11.3, 2.5 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.93 (dd, J = 8.2, 2.3 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.03 (d, J = 2.3 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H) |
이하, 참고 화합물 5-1, 5-3∼5-6 및 5-10∼5-11로부터 선택되는 화합물을 사용하고, 화합물 4-1의 제조 방법에 준하여, 화합물 4-2∼4-36을 얻었다.
6-(4-벤질술포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-2) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.70 (s, 3 H), 4.58 (d, J = 12.1 Hz, 1 H), 4.97 (s, 2 H), 5.05 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.37 (dd, J = 11.3, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 2.3 Hz, 1 H), 6.83 (dd, J = 8.2, 2.3 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.41-7.44 (m, 3 H), 7.47-7.49 (m, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-3) |
1 H-NMR (400 MHz, DMSO- d6) δ 1.01 (t, J = 7.5 Hz, 3 H), 1.07 (s, 3 H), 1.15 (s, 3 H), 1.83 (sextet, J = 7.5 Hz, 2 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 3.48 (t, J = 7.5 Hz, 2 H), 3.75 (s, 3 H), 4.58 (d, J = 12.0 Hz, 1 H), 5.05 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.36 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.77 (d, J = 8.1 Hz, 1 H), 6.91 (dd, J = 8.3, 2.4 Hz, 1 H), 6.98 (d, J = 2.4 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.23 (d, J = 8.3 Hz, 1 H) |
6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-4) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.15 (s, 3 H), 1.35 (t, J = 7.3 Hz, 3 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 3.50 (q, J = 7.3 Hz, 2 H), 3.75 (s, 3 H), 4.58 (d, J = 12.0 Hz, 1 H), 5.05 (d, J = 12.0 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.36 (dd, J = 11.5, 2.5 Hz, 1 H), 6.53 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.91 (dd, J = 8.3, 2.4 Hz, 1 H), 6.98 (d, J = 2.4 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.23 (d, J = 8.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소프로필설포닐옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-5) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.15 (s, 3 H), 1.42 (d, J = 6.7 Hz, 6 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.70 (septet, J = 6.7 Hz, 1 H), 3.75 (s, 3 H), 4.58 (d, J = 12.2 Hz, 1 H), 5.05 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.37 (dd, J = 11.3, 2.5 Hz, 1 H), 6.53 (td, J = 8.5, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.2, 2.4 Hz, 1 H), 6.95 (d, J = 2.4 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.23 (d, J = 8.2 Hz, 1 H) |
6-(4-부틸설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-6) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.89 (t, J = 7.6 Hz, 3 H), 1.07 (s, 3 H), 1.15 (s, 3 H), 1.42 (sextet, J = 7.6 Hz, 2 H), 1.78 (quintet, J = 7.6 Hz, 2 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 3.49 (t, J = 7.6 Hz, 2 H), 3.75 (s, 3 H), 4.58 (d, J = 12.1 Hz, 1 H), 5.05 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.36 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.92 (dd, J = 8.3, 2.3 Hz, 1 H), 6.98 (d, J = 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.23 (d, J = 8.3 Hz, 1 H) |
5-(2-메톡시-5-니트로페녹시메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-7) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.99 (t, J = 7.3 Hz, 3 H), 1.06 (s, 3 H), 1.18 (s, 3 H), 1.81 (tq, J = 7.6, 7.3 Hz, 2 H), 2.14 (s, 3 H), 3.44 (t, J = 7.6 Hz, 2 H), 3.71 (s, 3 H), 3.82 (s, 3 H), 4.63 (d, J = 11.9 Hz, 1 H), 5.23 (d, J = 11.9 Hz, 1 H), 5.41 (s, 1 H), 6.05 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.83 (dd, J = 8.2, 2.4 Hz, 1 H), 6.92 (d, J = 2.4 Hz, 1 H), 7.08 (d, J = 9.1 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.32 (d, J = 2.7 Hz, 1 H), 7.81 (dd, J = 9.1, 2.7 Hz, 1 H) |
6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-8) |
1 H-NMR (400 MHz, CDCl3) δ 1.04 (s, 3 H), 1.08-1.12 (m, 2 H), 1.23-1.26 (m, 2 H), 1.27 (s, 3 H), 2.27 (s, 3 H), 2.55-2.61 (m, 1 H), 3.77 (s, 3 H), 3.84 (s, 3 H), 4.77 (d, J = 12.4 Hz, 1 H), 5.35 (d, J = 12.4 Hz, 1 H), 5.47 (s, 1 H), 6.07 (s, 1 H), 6.56 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 9.0 Hz, 1 H), 6.85 (d, J = 8.2 Hz, 1 H), 6.86 (d, J = 2.2 Hz, 1 H), 6.90 (dd, J = 8.3, 2.2 Hz, 1 H), 7.27 (d, J = 2.7 Hz, 1 H), 7.30 (d, J = 8.3 Hz, 1 H), 7.78 (dd, J = 9.0, 2.7 Hz, 1 H) |
6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-9) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.18 (s, 3 H), 1.39 (d, J = 6.7 Hz, 6 H), 2.14 (s, 3 H), 3.62-3.67 (m, 1 H), 3.71 (s, 3 H), 3.82 (s, 3 H), 4.61 (d, J = 11.9 Hz, 1 H), 5.23 (d, J = 11.9 Hz, 1 H), 5.41 (s, 1 H), 6.05 (s, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 6.82 (dd, J = 8.2, 2.4 Hz, 1 H), 6.89 (d, J = 2.4 Hz, 1 H), 7.08 (d, J = 9.1 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.32 (d, J = 2.7 Hz, 1 H), 7.81 (dd, J = 9.1, 2.7 Hz, 1 H) |
5-(2-메톡시-5-니트로페녹시메틸)-6-[2-메톡시-4-(3,3,3-트리플루오르프로필설포닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-10) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.18 (s, 3 H), 2.14 (s, 3 H), 2.92-2.95 (m, 2 H), 3.71 (s, 3 H), 3.78-3.82 (m, 2 H), 3.82 (s, 3 H), 4.62 (d, J = 11.9 Hz, 1 H), 5.23 (d, J = 11.9 Hz, 1 H), 5.41 (s, 1 H), 6.06 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.89 (dd, J = 8.3, 2.4 Hz, 1 H), 7.01 (d, J = 2.4 Hz, 1 H), 7.07 (d, J = 9.1 Hz, 1 H), 7.21 (d, J = 8.3 Hz, 1 H), 7.32 (d, J = 2.6 Hz, 1 H), 7.81 (dd, J = 9.1, 2.6 Hz, 1 H) |
6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-11) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.93 (s, 3 H), 1.18 (s, 3 H), 1.35 (t, J = 7.3 Hz, 3 H), 2.13 (s, 3 H), 2.17 (s, 3 H), 3.51 (q, J = 7.3 Hz, 2 H), 3.76 (s, 3 H), 4.76 (d, J = 12.6 Hz, 1 H), 5.29 (d, J = 12.6 Hz, 1 H), 5.41 (s, 1 H), 6.07 (s, 1 H), 6.62 (d, J = 8.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.95 (dd, J = 8.2, 2.3 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 7.15 (d, J = 2.1 Hz, 1 H), 7.31 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.64 (dd, J = 8.2, 2.1 Hz, 1 H) |
6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-12) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.93 (s, 3 H), 1.01 (t, J = 7.5 Hz, 3 H), 1.18 (s, 3 H), 1.80-1.87 (m, 2 H), 2.13 (s, 3 H), 2.17 (s, 3 H), 3.49 (t, J = 7.6 Hz, 2 H), 3.76 (s, 3 H), 4.76 (d, J = 12.5 Hz, 1 H), 5.29 (d, J = 12.5 Hz, 1 H), 5.41 (s, 1 H), 6.07 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.94 (dd, J = 8.2, 2.4 Hz, 1 H), 6.98 (d, J = 2.4 Hz, 1 H), 7.15 (d, J = 2.2 Hz, 1 H), 7.31 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 1 H), 7.64 (dd, J = 8.0, 2.2 Hz, 1 H) |
6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-13) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.93 (s, 3 H), 1.18 (s, 3 H), 1.42 (d, J = 6.7 Hz, 6 H), 2.13 (s, 3 H), 2.17 (s, 3 H), 3.68-3.74 (m, 1 H), 3.76 (s, 3 H), 4.75 (d, J = 12.5 Hz, 1 H), 5.28 (d, J = 12.5 Hz, 1 H), 5.41 (s, 1 H), 6.07 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.93 (dd, J = 8.2, 2.2 Hz, 1 H), 6.95 (d, J = 2.2 Hz, 1 H), 7.16 (d, J = 2.1 Hz, 1 H), 7.31 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.64 (dd, J = 8.2, 2.1 Hz, 1 H) |
6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-14) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.89-0.94 (m, 2 H), 1.04-1.08 (m, 2 H), 1.08 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.01 (tt, J = 7.9, 4.9 Hz, 1 H), 3.75 (s, 3 H), 4.56 (d, J = 12.1 Hz, 1 H), 5.04 (d, J = 12.1 Hz, 1 H), 5.41 (s, 1 H), 6.07 (s, 1 H), 6.38 (dd, J = 11.3, 2.4 Hz, 1 H), 6.53 (td, J = 8.6, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.93 (dd, J = 8.2, 2.4 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.03 (d, J = 2.4 Hz, 1 H), 7.22 (d, J = 8.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소부틸설포닐옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-15) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (d, J = 7.0 Hz, 6 H), 1.07 (s, 3 H), 1.15 (s, 3 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 2.21-2.26 (m, 1 H), 3.43 (d, J = 6.4 Hz, 2 H), 3.75 (s, 3 H), 4.59 (d, J = 12.1 Hz, 1 H), 5.05 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.36 (dd, J = 11.5, 2.6 Hz, 1 H), 6.53 (td, J = 8.5, 2.6 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.92 (dd, J = 8.3, 2.2 Hz, 1 H), 6.98 (d, J = 2.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.23 (d, J = 8.3 Hz, 1 H) |
6-(4-시클로펜틸술포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-16) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.15 (s, 3 H), 1.57-1.65 (m, 2 H), 1.68-1.75 (m, 2 H), 1.95-2.02 (m, 2 H), 2.01 (s, 3 H), 2.04-2.11 (m, 2 H), 2.06 (s, 3 H), 3.75 (s, 3 H), 3.94 (tt, J = 8.9, 6.7 Hz, 1 H), 4.57 (d, J = 11.9 Hz, 1 H), 5.05 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.37 (dd, J = 11.3, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.2, 2.1 Hz, 1 H), 6.95 (d, J = 2.1 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.23 (d, J = 8.2 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3,3,3-트리플루오르프로필설포닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-17) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.07 (s, 3 H), 1.15 (s, 3 H), 2.00 (s, 3 H), 2.06 (s, 3 H), 2.90-3.00 (m, 2 H), 3.75 (s, 3 H), 3.83-3.87 (m, 2 H), 4.59 (d, J = 12.1 Hz, 1 H), 5.05 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.07 (s, 1 H), 6.35 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.97 (dd, J = 8.2, 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.06 (d, J = 2.3 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-18) |
1 H-NMR (400 MHz, DMSO-d6) δ 0.99 (t, J = 7.5 Hz, 3 H), 1.15 (s, 3 H), 1.21 (s, 3 H), 1.76-1.85 (m, 2 H), 2.07 (s, 3 H), 3.42-3.46 (m, 2 H), 3.68 (s, 3 H), 3.71 (s, 3 H), 3.83 (dd, J = 12.3, 3.5 Hz, 1 H), 4.00 (dd, J = 12.3, 6.7 Hz, 1 H), 4.18 (dd, J = 6.7, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.33 (dd, J = 7.7, 1.3 Hz, 1 H), 6.50 (td, J = 7.7, 1.3 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.66 (td, J = 7.7, 1.3 Hz, 1 H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.7, 1.3 Hz, 1 H), 6.88 (dd, J = 8.1, 2.1 Hz, 1 H), 6.90 (d, J = 2.1 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H) |
6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-19) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.39 (d, J = 6.8 Hz, 6 H), 2.07 (s, 3 H), 3.60-3.67 (m, 1 H), 3.69 (s, 3 H), 3.71 (s, 3 H), 3.83 (dd, J = 12.6, 3.5 Hz, 1 H), 4.00 (dd, J = 12.6, 6.6 Hz, 1 H), 4.18 (dd, J = 6.6, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.33 (dd, J = 7.7, 1.3 Hz, 1 H), 6.51 (td, J = 7.7, 1.3 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.67 (td, J = 7.7, 1.3 Hz, 1 H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.7, 1.3 Hz, 1 H), 6.87 (d, J = 2.3 Hz, 1 H), 6.87 (dd, J = 8.8, 2.3 Hz, 1 H), 7.17 (d, J = 8.8 Hz, 1 H) |
6-(2-메톡시-4-메틸설포닐옥시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-20) |
1 H-NMR (500 MHz, CDCl3) δ 1.26 (s, 3 H), 1.30 (s, 3 H), 2.19 (s, 3 H), 3.01 (s, 3 H), 3.70 (s, 3 H), 3.75 (s, 3 H), 3.89 (brs, 1 H), 4.00 (d, J = 12.4 Hz, 1 H), 4.06 (d, J = 12.4 Hz, 1 H), 4.28 (s, 1 H), 5.47 (s, 1 H), 6.34 (dd, J = 7.8, 1.3 Hz, 1 H), 6.56 (td, J = 7.8, 1.3 Hz, 1 H), 6.56 (d, J = 7.9 Hz, 1 H), 6.68 (dd, J = 7.8, 1.3 Hz, 1 H), 6.75 (td, J = 7.8, 1.3 Hz, 1 H), 6.78 (d, J = 2.2 Hz, 1 H), 6.81 (d, J = 7.9 Hz, 1 H), 6.82 (dd, J = 8.1, 2.2 Hz, 1 H), 7.18 (d, J = 8.1 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-21) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.00 (t, J = 7.5 Hz, 3 H), 1.11 (s, 3 H), 1.19 (s, 3 H), 1.78-1.86 (m, 2 H), 1.88 (s, 3 H), 2.05 (s, 3 H), 3.43-3.48 (m, 2 H), 3.73 (s, 3 H), 3.89 (dd, J = 13.1, 4.9 Hz, 1 H), 4.07 (dd, J = 13.1, 4.3 Hz, 1 H), 4.20-4.23 (m, 1 H), 5.41 (s, 1 H), 6.03 (dd, J = 12.2, 2.5 Hz, 1 H), 6.04 (s, 1 H), 6.19 (td, J = 8.5, 2.5 Hz, 1 H), 6.61 (d, J = 8.1 Hz, 1 H), 6.72 (d, J = 8.1 Hz, 1 H), 6.84-6.88 (m, 1 H), 6.91 (dd, J = 8.2, 2.4 Hz, 1 H), 6.95 (d, J = 2.4 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H) |
6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-22) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.80-1.05 (m, 4 H), 1.15 (s, 3 H), 1.22 (s, 3 H), 2.09 (s, 3 H), 2.91 (tt, J = 7.9, 4.9 Hz, 1 H), 3.68 (s, 3 H), 3.71 (s, 3 H), 3.81 (dd, J = 12.4, 3.4 Hz, 1 H), 3.99 (dd, J = 12.4, 6.2 Hz, 1 H), 4.18 (dd, J = 6.2, 3.4 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.32 (dd, J = 7.8, 1.2 Hz, 1 H), 6.50 (td, J = 7.8, 1.2 Hz, 1 H), 6.61 (d, J = 8.4 Hz, 1 H), 6.66 (td, J = 7.8, 1.2 Hz, 1 H), 6.71 (d, J = 8.4 Hz, 1 H), 6.72 (dd, J = 7.8, 1.2 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1 H), 6.96 (d, J = 2.2 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H) |
6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-23) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.32 (t, J = 7.3 Hz, 3 H), 2.08 (s, 3 H), 3.44 (q, J = 7.3 Hz, 2 H), 3.69 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.4, 3.7 Hz, 1 H), 3.99 (dd, J = 12.4, 6.3 Hz, 1 H), 4.18 (dd, J = 6.3, 3.7 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.33 (dd, J = 7.8, 1.3 Hz, 1 H), 6.50 (td, J = 7.8, 1.3 Hz, 1 H), 6.60 (d, J = 8.1 Hz, 1 H), 6.66 (td, J = 7.8, 1.3 Hz, 1 H), 6.70 (d, J = 8.1 Hz, 1 H), 6.73 (dd, J = 7.8, 1.3 Hz, 1 H), 6.88 (dd, J = 8.2, 2.4 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H) |
6-(4-시클로펜틸술포닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-24) |
1 H-NMR (500 MHz, DMSO-d6) δ1.15 (s, 3 H), 1.21 (s, 3 H), 1.55-1.63 (m, 2 H), 1.65-1.73 (m, 2 H), 1.92-1.99 (m, 2 H), 2.00-2.07 (m, 2 H), 2.07 (s, 3 H), 3.69 (s, 3 H), 3.71 (s, 3 H), 3.83 (dd, J = 12.7, 3.9 Hz, 1 H), 3.85-3.91 (m, 1 H), 3.99 (dd, J = 12.7, 6.2 Hz, 1 H), 4.18 (dd, J = 6.2, 3.9 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.33 (dd, J = 7.8, 1.2 Hz, 1 H), 6.50 (td, J = 7.8, 1.2 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.66 (td, J = 7.8, 1.2 Hz, 1 H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.8, 1.2 Hz, 1 H), 6.87 (d, J = 2.3 Hz, 1 H), 6.87 (dd, J = 8.9, 2.3 Hz, 1 H), 7.17 (d, J = 8.9 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-(2-메톡시-4-메틸설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-25) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.11 (s, 3 H), 1.19 (s, 3 H), 1.88 (s, 3 H), 2.05 (s, 3 H), 3.34 (s, 3 H), 3.74 (s, 3 H), 3.90 (dd, J = 13.1, 4.4 Hz, 1 H), 4.08 (dd, J = 13.1, 4.4 Hz, 1 H), 4.23 (t, J = 4.4 Hz, 1 H), 5.41 (s, 1 H), 6.02 (dd, J = 12.2, 2.4 Hz, 1 H), 6.04 (s, 1 H), 6.19 (td, J = 8.5, 2.4 Hz, 1 H), 6.61 (d, J = 8.2 Hz, 1 H), 6.72 (d, J = 8.2 Hz, 1 H), 6.85-6.88 (m, 1 H), 6.92 (dd, J = 8.2, 2.3 Hz, 1 H), 7.00 (d, J = 2.3 Hz, 1 H), 7.26 (d, J = 8.2 Hz, 1 H) |
6-[2-메톡시-4-(3,3,3-트리플루오르프로필설포닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-26) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.10 (s, 3 H), 2.46 (s, 3 H), 2.94-3.01 (m, 2 H), 3.69 (s, 3 H), 3.88 (t, J = 7.9 Hz, 2 H), 4.90 (d, J = 12.6 Hz, 1 H), 5.16 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.14 (s, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.88 (d, J = 3.9 Hz, 1 H), 6.94 (dd, J = 8.3, 2.2 Hz, 1 H), 7.04 (d, J = 2.2 Hz, 1 H), 7.22 (d, J = 8.3 Hz, 1 H), 7.46 (d, J = 3.9 Hz, 1 H) |
6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-27) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.02 (t, J = 7.5 Hz, 3 H), 1.12 (s, 3 H), 1.19 (s, 3 H), 1.84 (sextet, J = 7.5 Hz, 2 H), 2.08 (s, 3 H), 2.44 (s, 3 H), 3.47 (t, J = 7.5 Hz, 2 H), 3.73 (s, 3 H), 4.88 (d, J = 12.6 Hz, 1 H), 5.14 (d, J = 12.6 Hz, 1 H), 5.45 (s, 1 H), 6.07 (s, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.74 (d, J = 8.3 Hz, 1 H), 6.87 (d, J = 3.7 Hz, 1 H), 6.87 (dd, J = 8.3, 2.3 Hz, 1 H), 6.92 (d, J = 2.3 Hz, 1 H), 7.18 (d, J = 8.3 Hz, 1 H), 7.44 (d, J = 3.7 Hz, 1 H) |
6-(4-이소부틸설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-28) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.08 (d, J = 6.7 Hz, 6 H), 1.14 (s, 3 H), 1.21 (s, 3 H), 2.10 (s, 3 H), 2.22-2.30 (m, 1 H), 2.47 (s, 3 H), 3.45 (d, J = 6.7 Hz, 2 H), 3.68 (s, 3 H), 4.89 (d, J = 12.5 Hz, 1 H), 5.15 (d, J = 12.5 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 6.89 (dd, J = 8.2, 2.4 Hz, 1 H), 6.95 (d, J = 2.4 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.46 (d, J = 3.6 Hz, 1 H) |
6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-29) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 1.44 (d, J = 6.8 Hz, 6 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.69 (s, 3 H), 3.73 (heptet, J = 6.6 Hz, 1 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.16 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.13 (s, 1 H), 6.66 (d, J = 8.3 Hz, 1 H), 6.75 (d, J = 8.3 Hz, 1 H), 6.88 (d, J = 3.7 Hz, 1 H), 6.89 (dd, J = 8.3, 2.3 Hz, 1 H), 6.93 (d, J = 2.3 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.46 (d, J = 3.7 Hz, 1 H) |
6-(4-시클로펜틸술포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-30) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 1.60-1.67 (m, 2 H), 1.70-1.77 (m, 2 H), 1.97-2.04 (m, 2 H), 2.05-2.14 (m, 2 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.69 (s, 3 H), 3.97 (tt, J = 8.9, 6.9 Hz, 1 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.15 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.88 (d, J = 3.8 Hz, 1 H), 6.88 (dd, J = 8.1, 2.6 Hz, 1 H), 6.92 (d, J = 2.6 Hz, 1 H), 7.19 (d, J = 8.1 Hz, 1 H), 7.46 (d, J = 3.8 Hz, 1 H) |
6-(2-메톡시-4-메틸설포닐옥시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-31) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.39 (s, 3 H), 3.68 (s, 3 H), 4.91 (d, J = 12.7 Hz, 1 H), 5.16 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.13 (s, 1 H), 6.66 (d, J = 8.3 Hz, 1 H), 6.76 (d, J = 8.3 Hz, 1 H), 6.88 (d, J = 3.8 Hz, 1 H), 6.91 (dd, J = 8.3, 2.3 Hz, 1 H), 7.01 (d, J = 2.3 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.46 (d, J = 3.8 Hz, 1 H) |
6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-32) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 1.38 (t, J = 7.3 Hz, 3 H), 2.09 (s, 3 H), 2.47 (s, 3 H), 3.58 (q, J = 7.3 Hz, 2 H), 3.69 (s, 3 H), 4.90 (d, J = 12.7 Hz, 1 H), 5.15 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.12 (s, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 6.89 (dd, J = 8.3, 2.3 Hz, 1 H), 6.96 (d, J = 2.3 Hz, 1 H), 7.20 (d, J = 8.3 Hz, 1 H), 7.46 (d, J = 3.6 Hz, 1 H) |
6-(4-부틸설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-33) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.91 (t, J = 7.3 Hz, 3 H), 1.14 (s, 3 H), 1.21 (s, 3 H), 1.40-1.49 (m, 2 H), 1.77-1.84 (m, 2 H), 2.10 (s, 3 H), 2.47 (s, 3 H), 3.50-3.57 (m, 2 H), 3.68 (s, 3 H), 4.90 (d, J = 12.7 Hz, 1 H), 5.15 (d, J = 12.7 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.88 (d, J = 3.8 Hz, 1 H), 6.89 (dd, J = 8.2, 2.1 Hz, 1 H), 6.96 (d, J = 2.1 Hz, 1 H), 7.20 (d, J = 8.2 Hz, 1 H), 7.46 (d, J = 3.8 Hz, 1 H) |
6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-34) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.98-1.04 (m, 2 H), 1.12-1.19 (m, 2 H), 1.15 (s, 3 H), 1.21 (s, 3 H), 2.10 (s, 3 H), 2.46 (s, 3 H), 3.02-3.12 (m, 1 H), 3.68 (s, 3 H), 4.90 (d, J = 12.5 Hz, 1 H), 5.14 (d, J = 12.5 Hz, 1 H), 5.45 (s, 1 H), 6.11 (s, 1 H), 6.66 (d, J = 8.1 Hz, 1 H), 6.76 (d, J = 8.1 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 6.91 (dd, J = 8.2, 2.1 Hz, 1 H), 7.00 (d, J = 2.1 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.46 (d, J = 3.6 Hz, 1 H) |
6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-35) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.03 (t, J = 7.3 Hz, 3 H), 1.14 (s, 3 H), 1.22 (s, 3 H), 1.81-1.88 (m, 2 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.48-3.51 (m, 2 H), 3.68 (s, 3 H), 4.96 (d, J = 12.7 Hz, 1 H), 5.19 (d, J = 12.7 Hz, 1 H), 5.46 (s, 1 H), 6.13 (s, 1 H), 6.67 (d, J = 8.1 Hz, 1 H), 6.76 (d, J = 8.1 Hz, 1 H), 6.88 (dd, J = 8.2, 2.3 Hz, 1 H), 6.94 (d, J = 2.3 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 2 H), 7.70 (d, J = 8.2 Hz, 2 H) |
6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 4-36) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.23 (s, 3 H), 1.43 (d, J = 6.8 Hz, 6 H), 2.09 (s, 3 H), 2.35 (s, 3 H), 3.68 (s, 3 H), 3.68-3.75 (m, 1 H), 4.96 (d, J = 12.8 Hz, 1 H), 5.19 (d, J = 12.8 Hz, 1 H), 5.46 (s, 1 H), 6.13 (s, 1 H), 6.67 (d, J = 8.3 Hz, 1 H), 6.77 (d, J = 8.3 Hz, 1 H), 6.87 (dd, J = 8.2, 2.3 Hz, 1 H), 6.92 (d, J = 2.3 Hz, 1 H), 7.21 (d, J = 8.2 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 2 H), 7.70 (d, J = 8.2 Hz, 2 H) |
(실시예 5)
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-메톡시카르보닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-1)
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1, 25.0 mg, 0.058 mmol)를 테트라하이드로퓨란(0.5 mL)에 용해하고, 트리에틸아민(23 ㎕, 0.17 mmol), 클로로 탄산메틸(6.8 ㎕, 0.088 mmol)를 가하여, 실온에서 20분간 교반하였다. 반응액을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (28.0 mg)를 무색 아몰퍼스로서 얻었다. (수율 99%)
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.72 (s, 3 H), 3.83 (s, 3 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.07 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.04 (s, 1 H), 6.35 (dd, J = 11.3, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.82 (dd, J = 8.2, 2.3 Hz, 1 H), 6.98 (d, J = 2.3 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.19 (d, J = 8.2 Hz, 1 H) |
이하, 참고 화합물 5-1, 5-4, 5-6 및 5-10으로부터 선택되는 화합물을 사용하고, 화합물 5-1의 제조 방법에 준하여, 화합물 5-2∼5-11을 얻었다.
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-페녹시카르보닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-2) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.75 (s, 3 H), 4.62 (d, J = 12.2 Hz, 1 H), 5.08 (d, J = 12.2 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.36 (dd, J = 11.3, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.97 (dd, J = 8.2, 2.4 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.14 (d, J = 2.4 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.39 (d, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.6 Hz, 2 H) |
6-[4-(2-클로로페녹시카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-3) |
1 H-NMR (400 MHz, DMSO-d6) δ1.06 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.76 (s, 3 H), 4.61 (d, J = 11.9 Hz, 1 H), 5.07 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.37 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.5 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.96 (dd, J = 8.3, 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.10 (d, J = 2.3 Hz, 1 H), 7.25 (d, J = 8.3 Hz, 1 H), 7.39 (td, J = 7.9, 1.6 Hz, 1 H), 7.48 (td, J = 7.9, 1.7 Hz, 1 H), 7.61 (dd, J = 7.9, 1.6 Hz, 1 H), 7.66 (dd, J = 7.9, 1.7 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시페녹시카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-4) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.76 (s, 3 H), 3.86 (s, 3 H), 4.62 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.36 (dd, J = 11.3, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.91 (dd, J = 8.2, 2.3 Hz, 1 H), 7.01 (td, J = 8.0, 1.4 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.05 (d, J = 2.3 Hz, 1 H), 7.20 (dd, J = 8.0, 1.4 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.31 (td, J = 8.0, 1.6 Hz, 1 H), 7.35 (dd, J = 8.0, 1.6 Hz, 1 H) |
6-(4-벤질옥시카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-5) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.72 (s, 3 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.27 (s, 2 H), 5.39 (s, 1 H), 6.04 (s, 1 H), 6.35 (dd, J = 11.3, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.84 (dd, J = 8.2, 2.3 Hz, 1 H), 7.00 (d, J = 2.3 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.37-7.47 (m, 5 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2,2,2-트리클로로에톡시카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-6) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.74 (s, 3 H), 4.61 (d, J = 11.1 Hz, 1 H), 5.06 (s, 2 H), 5.07 (d, J = 11.1 Hz, 1 H), 5.40 (s, 1 H), 6.06 (s, 1 H), 6.36 (dd, J = 11.5, 2.4 Hz, 1 H), 6.53 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.2 Hz, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.3, 2.2 Hz, 1 H), 7.02-7.06 (m, 1 H), 7.05 (d, J = 2.2 Hz, 1 H), 7.23 (d, J = 8.3 Hz, 1 H) |
6-[4-(4-클로로페녹시카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-7) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.05 (s, 3 H), 1.18 (s, 3 H), 2.14 (s, 3 H), 3.71 (s, 3 H), 3.81 (s, 3 H), 4.65 (d, J = 11.9 Hz, 1 H), 5.25 (d, J = 11.9 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.90 (dd, J = 8.2, 2.3 Hz, 1 H), 7.08 (d, J = 9.1 Hz, 1 H), 7.10 (d, J = 2.3 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.31 (d, J = 2.7 Hz, 1 H), 7.43 (d, J = 8.9 Hz, 2 H), 7.55 (d, J = 8.9 Hz, 2 H), 7.81 (dd, J = 9.1, 2.7 Hz, 1 H) |
6-(2-메톡시-4-메톡시카르보닐옥시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-8) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 3.65 (s, 3 H), 3.71 (s, 3 H), 3.82 (s, 3 H), 3.84 (dd, J = 12.8, 3.5 Hz, 1 H), 4.01-4.05 (m, 1 H), 4.21 (dd, J = 6.6, 3.5 Hz, 1 H), 5.39 (s, 1 H), 6.00 (s, 1 H), 6.34 (dd, J = 7.8, 1.3 Hz, 1 H), 6.51 (td, J = 7.8, 1.3 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.67 (td, J = 7.8, 1.3 Hz, 1 H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.8, 1.3 Hz, 1 H), 6.79 (dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 2.2 Hz, 1 H), 7.11 (d, J = 8.2 Hz, 1 H) |
6-(4-클로로페닐옥시카르보닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-9) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.07 (s, 3 H), 3.68 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.6, 3.4 Hz, 1 H), 4.04 (dd, J = 12.6, 6.5 Hz, 1 H), 4.22 (dd, J = 6.5, 3.4 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.35 (dd, J = 7.9, 1.3 Hz, 1 H), 6.50 (td, J = 7.9, 1.3 Hz, 1 H), 6.61 (d, J = 8.3 Hz, 1 H), 6.67 (td, J = 7.9, 1.3 Hz, 1 H), 6.71 (d, J = 8.3 Hz, 1 H), 6.73 (dd, J = 7.9, 1.3 Hz, 1 H), 6.93 (dd, J = 8.1, 2.4 Hz, 1 H), 7.06 (d, J = 2.4 Hz, 1 H), 7.16 (d, J = 8.1 Hz, 1 H), 7.43 (d, J = 9.0 Hz, 2 H), 7.54 (d, J = 9.0 Hz, 2 H) |
6-(2-메톡시-4-메톡시카르보닐옥시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-10) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.08 (s, 3 H), 2.47 (s, 3 H), 3.66 (s, 3 H), 3.84 (s, 3 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.16 (d, J = 12.7 Hz, 1 H), 5.44 (s, 1 H), 6.10 (s, 1 H), 6.66 (d, J = 8.3 Hz, 1 H), 6.76 (d, J = 8.3 Hz, 1 H), 6.80 (dd, J = 8.2, 2.2 Hz, 1 H), 6.88 (d, J = 3.7 Hz, 1 H), 6.95 (d, J = 2.2 Hz, 1 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H) |
6-[4-(4-클로로페녹시카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 5-11) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.06 (s, 3 H), 1.15 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.75 (s, 3 H), 4.61 (d, J = 12.1 Hz, 1 H), 5.07 (d, J = 12.1 Hz, 1 H), 5.40 (s, 1 H), 6.05 (s, 1 H), 6.36 (dd, J = 11.3, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H), 6.97 (dd, J = 8.2, 2.4 Hz, 1 H), 7.02-7.05 (m, 1 H), 7.15 (d, J = 2.4 Hz, 1 H), 7.23 (d, J = 8.2 Hz, 1 H), 7.45 (d, J = 9.1 Hz, 2 H), 7.55 (d, J = 9.1 Hz, 2 H) |
(실시예 6)
5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-페닐아미노카르보닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-1)
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1, 25.0 mg, 0.058 mmol)를 테트라하이드로퓨란(0.5 mL)에 용해하고, 트리에틸아민(19.3 ㎕, 0.138 mmol), 이소시안산페닐(9.5 ㎕, 0.087 mmol)를 가하여, 실온에서 2시간 교반하였다. 반응액을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (27.3 mg)를 무색 아몰퍼스로서 얻었다. (수율 86%)
1 H-NMR (400 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.88 (br s, 1 H), 4.76 (d, J = 12.0 Hz, 1 H), 5.12 (d, J = 12.0 Hz, 1 H), 5.46 (s, 1 H), 6.20 (dd, J = 11.2, 2.4 Hz, 1 H), 6.42 (td, J = 8.3, 2.4 Hz, 1 H), 6.59 (d, J = 8.3 Hz, 1 H), 6.82-6.84 (m, 2 H), 6.90-6.95 (m, 3 H), 7.11-7.14 (m, 1 H), 7.25-7.27 (m, 1 H), 7.36 (t, J = 8.0 Hz, 2 H), 7.47 (d, J = 8.0 Hz, 2 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-메틸아미노카르보닐옥시]-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-2)
6-(4-하이드록시-2-메톡시페닐)-5-[N-(2-메톡시페닐)-N-(9-플루오레닐메톡시카르보닐)아미노메틸]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 6, 25.0 mg, 0.0383 mmol), 1, 1'-카르보닐디이미다졸(62.0 mg, 0.382 mmol) 및 4-디메틸아미노 피리딘(0.5 mg, 0.004 mmol)의 혼합물을 무수 테트라하이드로퓨란(1 mL)에 용해하고, 실온에서 4.5시간 교반했다. N,N,N'-트리메틸 에틸렌 디아민(39.2 mg, 0.383 mmol)를 가하여, 60℃으로 2시간 교반했다. 반응액을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제하였다. 얻어진 무색 아몰퍼스를 N,N-디메틸포름아미드(1 mL)에 용해하고, 피페리딘(50 ㎕)을 가하였다. 반응액을 실온에서 15분간 교반한 후, 에틸아세테이트(20 mL)로 희석했다. 물 (15 mL) 및 포화 식염수(15 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(헥산-에틸아세테이트)로 정제함으로써 표기 화합물 (9.9 mg)를 무색 아몰퍼스로서 얻었다. (수율 47%)
1 H-NMR (500 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 2.17 (s, 3 H), 2.18 (s, 3 H), 2.38-2.47 (m, 2 H), 2.90, 3.02 (s, 3 H), 3.33-3.38 (m, 1 H), 3.43-3.48 (m, 1 H), 3.64 (s, 3 H), 3.71 (s, 3 H), 3.82-3.85 (m, 1 H), 4.05-4.06 (m, 1 H), 4.22-4.24 (m, 1 H), 5.39 (s, 1 H), 5.99 (s, 1 H), 6.35 (dd, J = 7.9, 1.2 Hz, 1 H), 6.51 (td, J = 7.9, 1.2 Hz, 1 H), 6.60 (d, J = 8.0 Hz, 1 H), 6.64-6.70 (m, 4 H), 6.73 (dd, J = 8.2, 1.1 Hz, 1 H), 7.06 (d, J = 8.2 Hz, 1 H) |
6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-3)
5-(5-플루오르-2-메틸페녹시메틸)-6-(4-하이드록시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(참고 화합물 5-1, 25 mg, 0.058 mmol)를 피리딘(1 mL)에 용해하고, 염화 N,N-디메틸카르바모일(6.9 ㎕, 0.075 mmol)를 가하여, 100℃에서 3시간 교반하였다. 반응액에 염화 N,N-디메틸카르바모일(3.0 ㎕, 0.033 mmol)를 가하여, 100℃에서 1시간 교반했다. 반응액을 에틸아세테이트(20 mL)로 희석했다. 0.2N 염산 수용액(75 mL), 물 (50 mL) 및 포화 식염수(50 mL)로 순차적으로 세정하고, 무수 황산 마그네슘으로 건조 후, 감압하 용매를 제거했다. 얻어진 잔류물을 실리카겔 컬럼 크로마토그래피(1회째:헥산-에틸아세테이트, 2회째:톨루엔-에틸아세테이트)로 정제함으로써 표기 화합물 (8.5 mg)를 무색 아몰퍼스로서 얻었다. (수율 29%)
1 H-NMR (400 MHz, CDCl3) δ 1.11 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.15 (s, 3 H), 3.03 (s, 3 H), 3.12 (s, 3 H), 3.75 (s, 3 H), 3.92 (br s, 1 H), 4.75 (d, J = 12.0 Hz, 1 H), 5.11 (d, J = 12.0 Hz, 1 H), 5.45 (s, 1 H), 6.19 (dd, J = 11.1, 2.5 Hz, 1 H), 6.41 (td, J = 8.3, 2.5 Hz, 1 H), 6.60 (br s, 1 H), 6.75 (br s, 2 H), 6.89-6.94 (m, 2 H), 7.23 (d, J = 8.1 Hz, 1 H) |
이하, 참고 화합물 5-1, 5-3∼5-6 및 5-10∼5-11로부터 선택되는 화합물을 사용하고, 화합물 6-1∼6-3 중 어느 하나의 제조 방법에 준하여, 화합물 6-4∼6-39를 얻었다.
6-[4-(2-클로로페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-4) |
1 H-NMR (400 MHz, CDCl3) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.08 (s, 3 H), 2.16 (s, 3 H), 3.77 (s, 3 H), 3.88 (br s, 1 H), 4.76 (d, J = 12.1 Hz, 1 H), 5.12 (d, J = 12.1 Hz, 1 H), 5.46 (s, 1 H), 6.20 (dd, J = 11.2, 2.5 Hz, 1 H), 6.43 (td, J = 8.4, 2.5 Hz, 1 H), 6.59 (d, J = 8.2 Hz, 1 H), 6.84 (d, J = 2.4 Hz, 1 H), 6.85 (dd, J = 8.2, 2.4 Hz, 1 H), 6.91 (d, J = 8.2 Hz, 1 H), 6.92-6.96 (m, 1 H), 7.03-7.08 (m, 1 H), 7.28 (d, J = 8.2 Hz, 1 H), 7.29-7.33 (m, 1 H), 7.40 (dd, J = 8.1, 1.5 Hz, 1 H), 7.50 (br s, 1 H), 8.21 (d, J = 7.1 Hz, 1 H) |
6-[4-(3-클로로페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-5) |
1 H-NMR (400 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.88 (br s, 1 H), 4.75 (d, J = 12.0 Hz, 1 H), 5.12 (d, J = 12.0 Hz, 1 H), 5.46 (s, 1 H), 6.20 (dd, J = 11.2, 2.4 Hz, 1 H), 6.42 (td, J = 8.3, 2.4 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.81-6.83 (m, 2 H), 6.91 (d, J = 8.1 Hz, 1 H), 6.92-6.95 (m, 1 H), 7.09-7.11 (m, 1 H), 7.25-7.32 (m, 4 H), 7.58 (br s, 1 H) |
6-[4-(4-클로로페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-6) |
1 H-NMR (500 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.87 (br s, 1 H), 4.75 (d, J = 12.2 Hz, 1 H), 5.11 (d, J = 12.2 Hz, 1 H), 5.46 (s, 1 H), 6.20 (dd, J = 11.3, 2.4 Hz, 1 H), 6.42 (td, J = 8.2, 2.4 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.81 (d, J = 1.9 Hz, 1 H), 6.82 (dd, J = 6.9, 1.9 Hz, 1 H), 6.90 (d, J = 8.1 Hz, 1 H), 6.92-6.95 (m, 1 H), 7.25-7.27 (m, 2 H), 7.32 (d, J = 8.7 Hz, 2 H), 7.42 (d, J = 8.7 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-3-일아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-7) |
1 H-NMR (500 MHz, CDCl3) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.91 (br s, 1 H), 4.75 (d, J = 12.1 Hz, 1 H), 5.12 (d, J = 12.1 Hz, 1 H), 5.46 (s, 1 H), 6.20 (dd, J = 11.0, 2.5 Hz, 1 H), 6.43 (td, J = 8.3, 2.5 Hz, 1 H), 6.59 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 2.3 Hz, 1 H), 6.83 (dd, J = 8.1, 2.3 Hz, 1 H), 6.90 (d, J = 8.2 Hz, 1 H), 6.92-6.95 (m, 1 H), 7.07 (br s, 1 H), 7.27 (d, J = 8.1 Hz, 1 H), 7.31 (dd, J = 7.5, 4.9 Hz, 1 H), 8.07 (d, J = 7.5 Hz, 1 H), 8.38 (dd, J = 4.9, 1.8 Hz, 1 H), 8.59 (d, J = 1.8 Hz, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시페닐아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-8) |
1 H-NMR (500 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.85 (br s, 1 H), 3.92 (s, 3 H), 4.76 (d, J = 12.2 Hz, 1 H), 5.12 (d, J = 12.2 Hz, 1 H), 5.45 (s, 1 H), 6.20 (dd, J = 11.3, 2.4 Hz, 1 H), 6.42 (td, J = 8.2, 2.4 Hz, 1 H), 6.59 (d, J = 7.9 Hz, 1 H), 6.83-6.85 (m, 2 H), 6.90-6.95 (m, 2 H), 6.91 (d, J = 7.9 Hz, 1 H), 6.99 (td, J = 7.8, 1.3 Hz, 1 H), 7.05 (td, J = 7.8, 1.6 Hz, 1 H), 7.25-7.27 (m, 1 H), 7.60 (br s, 1 H), 8.12 (br s, 1 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메톡시페닐아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-9) |
1 H-NMR (400 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.81 (s, 3 H), 3.86 (br s, 1 H), 4.75 (d, J = 12.0 Hz, 1 H), 5.12 (d, J = 12.0 Hz, 1 H), 5.45 (s, 1 H), 6.20 (dd, J = 11.1, 2.5 Hz, 1 H), 6.42 (td, J = 8.3, 2.5 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.68 (dd, J = 7.9, 2.1 Hz, 1 H), 6.81-6.84 (m, 2 H), 6.90 (d, J = 8.3 Hz, 1 H), 6.91-6.95 (m, 3 H), 7.22-7.28 (m, 3 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메톡시페닐아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-10) |
1 H-NMR (400 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.81 (s, 3 H), 3.86 (br s, 1 H), 4.75 (d, J = 12.0 Hz, 1 H), 5.12 (d, J = 12.0 Hz, 1 H), 5.45 (s, 1 H), 6.20 (dd, J = 11.2, 2.4 Hz, 1 H), 6.42 (td, J = 8.3, 2.4 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.81-6.83 (m, 3 H), 6.88-6.95 (m, 3 H), 6.91 (d, J = 8.1 Hz, 1 H), 7.24-7.27 (m, 1 H), 7.38 (d, J = 8.3 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메톡시카르보닐페닐아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-11) |
1 H-NMR (400 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.08 (s, 3 H), 2.16 (s, 3 H), 3.77 (s, 3 H), 3.87 (br s, 1 H), 3.91 (s, 3 H), 4.75 (d, J = 12.1 Hz, 1 H), 5.12 (d, J = 12.1 Hz, 1 H), 5.46 (s, 1 H), 6.20 (dd, J = 11.2, 2.4 Hz, 1 H), 6.43 (td, J = 8.3, 2.4 Hz, 1 H), 6.59 (d, J = 8.1 Hz, 1 H), 6.82 (d, J = 1.9 Hz, 1 H), 6.83 (dd, J = 7.1, 1.9 Hz, 1 H), 6.91 (d, J = 8.1 Hz, 1 H), 6.92-6.96 (m, 1 H), 7.12 (br s, 1 H), 7.28 (d, J = 7.1 Hz, 1 H), 7.54 (d, J = 8.8 Hz, 2 H), 8.05 (d, J = 8.8 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(4-메틸페닐아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-12) |
1 H-NMR (500 MHz, CDCl3) δ 1.12 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 2.33 (s, 3 H), 3.76 (s, 3 H), 3.89 (br s, 1 H), 4.76 (d, J = 12.1 Hz, 1 H), 5.12 (d, J = 12.1 Hz, 1 H), 5.45 (s, 1 H), 6.20 (dd, J = 11.0, 2.4 Hz, 1 H), 6.42 (td, J = 8.4, 2.4 Hz, 1 H), 6.59 (d, J = 7.9 Hz, 1 H), 6.82-6.83 (m, 2 H), 6.87 (br s, 1 H), 6.90-6.95 (m, 2 H), 7.15 (d, J = 7.9 Hz, 2 H), 7.25 (d, J = 7.0 Hz, 1 H), 7.35 (d, J = 7.9 Hz, 2 H) |
6-[4-(4-시아노페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-13) |
1 H-NMR (500 MHz, CDCl3) δ 1.13 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 3.76 (s, 3 H), 3.91 (br s, 1 H), 4.74 (d, J = 11.9 Hz, 1 H), 5.11 (d, J = 11.9 Hz, 1 H), 5.46 (s, 1 H), 6.19 (dd, J = 11.2, 2.5 Hz, 1 H), 6.43 (td, J = 8.2, 2.5 Hz, 1 H), 6.59 (d, J = 8.2 Hz, 1 H), 6.81-6.83 (m, 2 H), 6.90 (d, J = 8.2 Hz, 1 H), 6.92-6.95 (m, 1 H), 7.16 (br s, 1 H), 7.28 (d, J = 8.2 Hz, 1 H), 7.60 (d, J = 8.9 Hz, 2 H), 7.65 (d, J = 8.9 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피페리딘-1-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-14) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.14 (s, 3 H), 1.55 (br s, 6 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.41 (br s, 2 H), 3.55 (br s, 2 H), 3.71 (s, 3 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.08 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.34 (dd, J = 11.2, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.71 (dd, J = 8.2, 2.2 Hz, 1 H), 6.77 (d, J = 8.3 Hz, 1 H), 6.83 (d, J = 2.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.14 (d, J = 8.2 Hz, 1 H) |
6-(4-이소프로필아미노카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-15) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.03 (s, 3 H), 1.13 (d, J = 6.6 Hz, 6 H), 1.14 (s, 3 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 3.64-3.68 (m, 1 H), 3.71 (s, 3 H), 4.63 (d, J = 12.3 Hz, 1 H), 5.08 (d, J = 12.3 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.32 (dd, J = 11.6, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.69 (dd, J = 8.1, 2.2 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1 H), 6.80 (d, J = 2.2 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.13 (d, J = 8.1 Hz, 1 H), 7.67 (d, J = 7.8 Hz, 1 H) |
6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-16) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.03 (s, 3 H), 1.18 (s, 3 H), 2.14 (s, 3 H), 3.41-3.64 (m, 8 H), 3.68 (s, 3 H), 3.82 (s, 3 H), 4.66 (d, J = 11.9 Hz, 1 H), 5.25 (d, J = 11.9 Hz, 1 H), 5.39 (s, 1 H), 6.01 (s, 1 H), 6.61 (d, J = 8.2 Hz, 1 H), 6.66 (dd, J = 8.2, 2.3 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 6.81 (d, J = 2.3 Hz, 1 H), 7.08 (d, J = 9.0 Hz, 1 H), 7.12 (d, J = 8.2 Hz, 1 H), 7.30 (d, J = 2.7 Hz, 1 H), 7.81 (dd, J = 9.0, 2.7 Hz, 1 H) |
6-[4-[N-(2-디에틸아미노에틸)-N-메틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-17) |
1 H-NMR (400 MHz, CDCl3) δ 1.06 (t, J = 7.2 Hz, 6 H), 1.11 (s, 3 H), 1.22 (s, 3 H), 2.07 (s, 3 H), 2.15 (s, 3 H), 2.59 (q, J = 7.2 Hz, 4 H), 2.66-2.73 (m, 2 H), 3.05, 3.14 (s, 3 H), 3.42-3.52 (m, 2 H), 3.75 (s, 3 H), 4.76 (d, J = 11.5 Hz, 1 H), 5.11 (d, J = 11.5 Hz, 1 H), 5.44 (s, 1 H), 6.19 (dd, J = 11.2, 2.3 Hz, 1 H), 6.41 (td, J = 8.3, 2.3 Hz, 1 H), 6.57 (d, J = 8.1 Hz, 1 H), 6.73-6.77 (m, 2 H), 6.88-6.94 (m, 2 H), 7.22 (d, J = 8.3 Hz, 1 H) |
6-[4-[N-벤질-N-(2-디메틸아미노에틸)아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-18) |
1 H-NMR (400 MHz, CDCl3) δ 1.13 (s, 3 H), 1.25 (s, 3 H), 2.07 (s, 3 H), 2.16 (s, 3 H), 2.85 (s, 6 H), 3.13-3.23 (m, 2 H), 3.77 (s, 3 H), 3.81-3.96 (m, 2 H), 4.66-4.85 (m, 3 H), 5.11 (d, J = 12.2 Hz, 1 H), 5.47 (s, 1 H), 6.18 (dd, J = 11.1, 2.4 Hz, 1 H), 6.42 (td, J = 8.3, 2.4 Hz, 1 H), 6.65 (d, J = 7.8 Hz, 1 H), 6.79 (dd, J = 8.1, 1.7 Hz, 1 H), 6.88-6.96 (m, 3 H), 7.25 (d, J = 8.1 Hz, 1 H), 7.32-7.52 (m, 5 H) |
6-[4-[N-벤질-N-(2-디메틸아미노에틸)아미노카르보닐옥시]-2-메톡시페닐]-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-19) |
1 H-NMR (500 MHz, CDCl3) δ 0.99 (s, 3 H), 1.26 (s, 3 H), 2.24 (s, 3 H), 2.26 (s, 6 H), 2.50-2.51 (m, 2 H), 3.46 (t, J = 7.0 Hz, 2 H), 3.74, 3.77 (s, 3 H), 3.82, 3.83 (s, 3 H), 4.61, 4.70 (s, 2 H), 4.84-4.89 (m, 1 H), 5.36-5.41 (m, 1 H), 5.44 (s, 1 H), 6.55 (d, J = 7.6 Hz, 1 H), 6.67-6.88 (m, 4 H), 7.27-7.38 (m, 7 H), 7.76 (d, J = 8.9 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-에틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-20) |
1 H-NMR (500 MHz, CDCl3) δ 1.10 (s, 3 H), 1.22 (s, 3 H), 1.26 (t, J = 7.4 Hz, 3 H), 2.07 (s, 3 H), 2.15 (s, 3 H), 2.30 (s, 6 H), 2.52-2.59 (m, 2 H), 3.40-3.52 (m, 4 H), 3.75 (s, 3 H), 4.76 (d, J = 11.9 Hz, 1 H), 5.11 (d, J = 11.9 Hz, 1 H), 5.44 (s, 1 H), 6.19 (dd, J = 11.3, 2.4 Hz, 1 H), 6.41 (td, J = 8.4, 2.4 Hz, 1 H), 6.57 (d, J = 8.2 Hz, 1 H), 6.74-6.77 (m, 2 H), 6.87-6.94 (m, 2 H), 7.22 (d, J = 8.6 Hz, 1 H) |
5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일아미노카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-21) |
1 H-NMR (400 MHz, CDCl3) δ 1.26 (s, 3 H), 1.30 (s, 3 H), 2.17 (s, 3 H), 3.68 (s, 3 H), 3.75 (s, 3 H), 3.86 (brs, 1 H), 4.03 (d, J = 12.1 Hz, 1 H), 4.15 (d, J = 12.1 Hz, 1 H), 4.34 (s, 1 H), 5.46 (s, 1 H), 6.39 (dd, J = 7.7, 1.4 Hz, 1 H), 6.57 (d, J = 8.1 Hz, 1 H), 6.57 (td, J = 7.7, 1.4 Hz, 1 H), 6.70 (dd, J = 7.7, 1.4 Hz, 1 H), 6.71 (d, J = 2.3 Hz, 1 H), 6.77 (dd, J = 8.2, 2.3 Hz, 1 H), 6.78 (td, J = 7.7, 1.4 Hz, 1 H), 6.86 (d, J = 8.1 Hz, 1 H), 7.02 (s, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.30 (dd, J = 8.4, 4.8 Hz, 1 H), 8.02-8.07 (m, 1 H), 8.37 (dd, J = 4.8, 1.5 Hz, 1 H), 8.57 (d, J = 2.2 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-메틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-22) |
1 H-NMR (400 MHz, CDCl3) δ 1.24 (s, 3 H), 1.29 (s, 3 H), 1.93 (s, 3 H), 2.10 (s, 3 H), 2.30 (s, 6 H), 2.53-2.58 (m, 2 H), 3.04, 3.12 (s, 3 H), 3.47-3.55 (m, 2 H), 3.69 (s, 4 H), 4.09 (s, 3 H), 5.48 (s, 1 H), 6.08 (dd, J = 11.7, 2.4 Hz, 1 H), 6.23 (td, J = 8.4, 2.4 Hz, 1 H), 6.58 (d, J = 8.1 Hz, 1 H), 6.70-6.75 (m, 2 H), 6.85-6.88 (m, 2 H), 7.14 (d, J = 8.1 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-에틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-23) |
1 H-NMR (400 MHz, CDCl3) δ 1.21-1.27 (m, 3 H), 1.24 (s, 3 H), 1.29 (s, 3 H), 1.93 (s, 3 H), 2.10 (s, 3 H), 2.30 (s, 6 H), 2.53-2.58 (m, 2 H), 3.40-3.52 (m, 4 H), 3.70 (s, 4 H), 4.10 (s, 2 H), 5.48 (br s, 1 H), 6.08 (dd, J = 11.8, 2.4 Hz, 1 H), 6.23 (td, J = 8.4, 2.4 Hz, 1 H), 6.58 (d, J = 8.1 Hz, 1 H), 6.69-6.72 (m, 1 H), 6.74 (dd, J = 8.1, 2.2 Hz, 1 H), 6.84-6.89 (m, 2 H), 7.14 (d, J = 8.1 Hz, 1 H) |
6-[2-메톡시-4-(피리딘-3-일아미노카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-24) |
1 H-NMR (400 MHz, CDCl3) δ 1.26 (s, 3 H), 1.30 (s, 3 H), 2.19 (s, 3 H), 2.48 (s, 3 H), 3.71 (s, 3 H), 3.89 (s, 1 H), 5.02 (d, J = 12.7 Hz, 1 H), 5.33 (d, J = 12.7 Hz, 1 H), 5.51 (s, 1 H), 6.61 (d, J = 8.1 Hz, 1 H), 6.71 (d, J = 3.7 Hz, 1 H), 6.76 (s, 1 H), 6.77 (dd, J = 8.4, 2.2 Hz, 1 H), 6.90 (d, J = 8.1 Hz, 1 H), 7.06 (s, 1 H), 7.23 (d, J = 8.4 Hz, 1 H), 7.31 (dd, J = 8.3, 4.8 Hz, 1 H), 7.50 (d, J = 3.7 Hz, 1 H), 8.07 (d, J = 8.3 Hz, 1 H), 8.37 (d, J = 4.8 Hz, 1 H), 8.59 (d, J = 2.2 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-메틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-25) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.08 (s, 3 H), 2.18 (s, 3 H), 2.20 (s, 3 H), 2.39-2.48 (m, 2 H), 2.47 (s, 3 H), 2.92, 3.05 (s, 3 H), 3.34-3.39 (m, 1 H), 3.48-3.50 (m, 1 H), 3.65 (s, 3 H), 4.89 (d, J = 12.7 Hz, 1 H), 5.17 (d, J = 12.7 Hz, 1 H), 5.44 (s, 1 H), 6.08 (s, 1 H), 6.64-6.70 (m, 1 H), 6.65 (d, J = 8.3 Hz, 1 H), 6.75 (d, J = 8.3 Hz, 1 H), 6.77-6.80 (m, 1 H), 6.88 (d, J = 3.8 Hz, 1 H), 7.10 (d, J = 8.3 Hz, 1 H), 7.47 (d, J = 3.8 Hz, 1 H) |
6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-26) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.08 (s, 3 H), 2.47 (s, 3 H), 3.39-3.47 (m, 2 H), 3.56-3.62 (m, 2 H), 3.64-3.67 (m, 4 H), 3.65 (s, 3 H), 4.88 (d, J = 12.6 Hz, 1 H), 5.17 (d, J = 12.6 Hz, 1 H), 5.44 (s, 1 H), 6.09 (s, 1 H), 6.65 (d, J = 8.2 Hz, 1 H), 6.71 (dd, J = 8.2, 2.2 Hz, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.83 (d, J = 2.2 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 7.11 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 3.6 Hz, 1 H) |
6-[4-(4-클로로페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-27) |
1 H-NMR (500 MHz, CDCl3) δ 1.25 (s, 3 H), 1.30 (s, 3 H), 2.18 (s, 3 H), 2.48 (s, 3 H), 3.70 (s, 3 H), 3.89 (br s, 1 H), 5.02 (d, J = 12.5 Hz, 1 H), 5.32 (d, J = 12.5 Hz, 1 H), 5.50 (s, 1 H), 6.61 (d, J = 8.2 Hz, 1 H), 6.71 (d, J = 3.9 Hz, 1 H), 6.75 (d, J = 2.4 Hz, 1 H), 6.76 (dd, J = 8.8, 2.4 Hz, 1 H), 6.89 (d, J = 8.2 Hz, 1 H), 6.97 (br s, 1 H), 7.21 (d, J = 8.8 Hz, 1 H), 7.31 (d, J = 8.9 Hz, 2 H), 7.43 (d, J = 8.9 Hz, 2 H), 7.49 (d, J = 3.9 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-에틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-28) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.22 (s, 3 H), 1.23 (t, J = 6.6 Hz, 3 H), 2.08 (s, 3 H), 2.18 (s, 3 H), 2.20 (s, 3 H), 2.37-2.41 (m, 2 H), 2.47 (s, 3 H), 3.32-3.45 (m, 4 H), 3.66 (s, 3 H), 4.90 (d, J = 12.6 Hz, 1 H), 5.17 (d, J = 12.6 Hz, 1 H), 5.44 (s, 1 H), 6.08 (s, 1 H), 6.65-6.68 (m, 1 H), 6.66 (d, J = 8.1 Hz, 1 H), 6.76 (d, J = 8.1 Hz, 1 H), 6.79 (br s, 1 H), 6.88 (d, J = 3.7 Hz, 1 H), 7.11 (d, J = 8.3 Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H) |
6-[4-[N-벤질-N-(2-디메틸아미노에틸)아미노카르보닐옥시]-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-29) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.14 (s, 3 H), 1.21 (s, 3 H), 2.09 (s, 3 H), 2.15 (s, 6 H), 2.40-2.45 (m, 2 H), 2.47 (s, 3 H), 3.35-3.43 (m, 2 H), 3.63-3.68 (m, 3 H), 4.55 (s, 1 H), 4.67 (s, 1 H), 4.88-4.92 (m, 1 H), 5.13-5.19 (m, 1 H), 5.44 (s, 1 H), 6.08 (s, 1 H), 6.61-6.77 (m, 2 H), 6.87-6.88 (m, 1 H), 7.09-7.14 (m, 1 H), 7.19-7.32 (m, 3 H), 7.34-7.39 (m, 4 H), 7.46-7.48 (m, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-메틸아미노카르보닐옥시]-2-메톡시페닐]-5-(4-메틸벤조일옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-30) |
1 H-NMR (500 MHz, CDCl3) δ 1.25 (s, 3 H), 1.30 (s, 3 H), 2.16 (s, 3 H), 2.30 (s, 6 H), 2.38 (s, 3 H), 2.53-2.57 (m, 2 H), 3.03, 3.11 (s, 3 H), 3.47-3.54 (m, 2 H), 3.68 (s, 3 H), 5.06 (d, J = 12.5 Hz, 1 H), 5.36 (d, J = 12.5 Hz, 1 H), 5.49 (s, 1 H), 6.61 (d, J = 8.2 Hz, 1 H), 6.67-6.70 (m, 2 H), 6.88-6.91 (m, 1 H), 7.17 (d, J = 8.2 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 2 H), 7.84 (d, J = 8.2 Hz, 2 H) |
5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-31) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.14 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.42 (br s, 2 H), 3.58 (br s, 2 H), 3.65 (t, J = 4.8 Hz, 4 H), 3.71 (s, 3 H), 4.61 (d, J = 12.2 Hz, 1 H), 5.07 (d, J = 12.2 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.34 (dd, J = 11.5, 2.4 Hz, 1 H), 6.52 (td, J = 8.4, 2.4 Hz, 1 H), 6.63 (d, J = 8.3 Hz, 1 H), 6.74 (dd, J = 8.1, 2.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 6.86 (d, J = 2.3 Hz, 1 H), 7.01-7.05 (m, 1 H), 7.15 (d, J = 8.1 Hz, 1 H) |
6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-32) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.89 (s, 3 H), 1.18 (s, 3 H), 2.12 (s, 3 H), 2.18 (s, 3 H), 3.38-3.48 (m, 2 H), 3.51-3.63 (m, 2 H), 3.63-3.67 (m, 4 H), 3.73 (s, 3 H), 4.77 (d, J = 12.5 Hz, 1 H), 5.31 (d, J = 12.5 Hz, 1 H), 5.40 (s, 1 H), 6.02 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.77 (dd, J = 8.2, 2.0 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.87 (d, J = 2.0 Hz, 1 H), 7.14 (d, J = 2.1 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.63 (dd, J = 8.2, 2.1 Hz, 1 H) |
6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-33) |
1 H-NMR (500 MHz, DMSO-d6) δ 0.89 (s, 3 H), 1.18 (s, 3 H), 2.12 (s, 3 H), 2.18 (s, 3 H), 2.92 (s, 3 H), 3.05 (s, 3 H), 3.73 (s, 3 H), 4.78 (d, J = 12.5 Hz, 1 H), 5.31 (d, J = 12.5 Hz, 1 H), 5.39 (s, 1 H), 6.02 (s, 1 H), 6.62 (d, J = 8.2 Hz, 1 H), 6.74 (dd, J = 8.2, 2.3 Hz, 1 H), 6.79 (d, J = 8.2 Hz, 1 H), 6.84 (d, J = 2.3 Hz, 1 H), 7.14 (d, J = 2.1 Hz, 1 H), 7.24 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H), 7.63 (dd, J = 8.2, 2.1 Hz, 1 H) |
6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-34) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H), 2.90 (s, 3 H), 3.02 (s, 3 H), 3.64 (s, 3 H), 3.71 (s, 3 H), 3.82 (dd, J = 12.1, 3.3 Hz, 1 H), 4.04 (dd, J = 12.1, 6.8 Hz, 1 H), 4.23 (dd, J = 6.8, 3.3 Hz, 1 H), 5.39 (s, 1 H), 5.99 (s, 1 H), 6.35 (dd, J = 7.8, 1.3 Hz, 1 H), 6.51 (td, J = 7.8, 1.3 Hz, 1 H), 6.60 (d, J = 8.3 Hz, 1 H), 6.67 (dd, J = 7.8, 1.3 Hz, 1 H), 6.68 (td, J = 7.8, 1.3 Hz, 1 H), 6.70 (d, J = 8.3 Hz, 1 H), 6.74 (dd, J = 8.1, 1.8 Hz, 1 H), 6.75 (d, J = 1.8 Hz, 1 H), 7.06 (d, J = 8.1 Hz, 1 H) |
6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-35) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.07 (s, 3 H), 3.38-3.43 (m, 2 H), 3.54-3.59 (m, 2 H), 3.61-3.64 (m, 4 H), 3.64 (s, 3 H), 3.71 (s, 3 H), 3.82 (dd, J = 13.1, 3.7 Hz, 1 H), 4.04 (dd, J = 13.1, 6.6 Hz, 1 H), 4.23 (dd, J = 6.6, 3.7 Hz, 1 H), 5.39 (s, 1 H), 5.99 (s, 1 H), 6.35 (dd, J = 7.7, 1.3 Hz, 1 H), 6.51 (td, J = 7.7, 1.3 Hz, 1 H), 6.60 (d, J = 8.3 Hz, 1 H), 6.65-6.75 (m, 4 H), 6.78 (d, J = 2.2 Hz, 1 H), 7.07 (d, J = 8.3 Hz, 1 H) |
5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-36) |
1 H-NMR (400 MHz, DMSO-d6) δ 1.10 (s, 3 H), 1.19 (s, 3 H), 1.90 (s, 3 H), 2.04 (s, 3 H), 3.38-3.44 (m, 2 H), 3.54-3.60 (m, 2 H), 3.63-3.66 (m, 4 H), 3.70 (s, 3 H), 3.91 (dd, J = 13.2, 4.8 Hz, 1 H), 4.06 (dd, J = 13.2, 4.8 Hz, 1 H), 4.19-4.23 (m, 1 H), 5.40 (s, 1 H), 6.01 (s, 1 H), 6.04 (dd, J = 12.1, 2.5 Hz, 1 H), 6.20 (td, J = 8.4, 2.5 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 8.2, 2.1 Hz, 1 H), 6.84 (d, J = 2.1 Hz, 1 H), 6.85-6.90 (m, 1 H), 7.16 (d, J = 8.2 Hz, 1 H) |
6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-37) |
1 H-NMR (500 MHz, CDCl3) δ1.25 (s, 3 H), 1.29 (s, 3 H), 2.17 (s, 3 H), 2.48 (s, 3 H), 3.02 (s, 3 H), 3.10 (s, 3 H), 3.69 (s, 3 H), 3.95 (br s, 1 H), 5.00 (d, J = 12.5 Hz, 1 H), 5.32 (d, J = 12.5 Hz, 1 H), 5.49 (s, 1 H), 6.60 (d, J = 7.9 Hz, 1 H), 6.68-6.71 (m, 3 H), 6.90 (d, J = 8.2 Hz, 1 H), 7.18 (d, J = 8.6 Hz, 1 H), 7.50 (d, J = 3.7 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-메틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-38) |
1 H-NMR (500 MHz, DMSO-d6) δ 1.04 (s, 3 H), 1.14 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 2.18 (s, 3 H), 2.20 (m, 3 H), 2.41-2.54 (m, 2 H), 2.92-3.04 (m, 3 H), 3.30-3.37 (m, 2 H), 3.71 (s, 3 H), 4.62 (d, J = 12.1 Hz, 1 H), 5.08 (d, J = 12.1 Hz, 1 H), 5.39 (s, 1 H), 6.01 (s, 1 H), 6.34 (dd, J = 11.8, 2.2 Hz, 1 H), 6.52 (td, J = 8.2, 2.2 Hz, 1 H), 6.63 (d, J = 7.9 Hz, 1 H), 6.68-6.72 (m, 1 H), 6.77 (d, J = 7.9 Hz, 1 H), 6.81-6.83 (m, 1 H), 7.02-7.05 (m, 1 H), 7.15 (d, J = 8.2 Hz, 1 H) |
6-[4-[N-(2-디메틸아미노에틸)-N-(피리딘-3-일메틸)아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린(화합물 6-39) |
1 H-NMR (500 MHz, CDCl3) δ 1.11 (s, 3 H), 1.23 (s, 3 H), 2.07 (s, 3 H), 2.15 (s, 3 H), 2.28 (s, 3 H), 2.30-2.34 (m, 3 H), 2.54-2.62 (m, 2 H), 3.50-3.54 (m, 2 H), 3.73-3.77 (m, 3 H), 4.64 (s, 1 H), 4.72-4.77 (m, 2 H), 5.08-5.13 (m, 1 H), 5.44 (s, 1 H), 6.17-6.21 (m, 1 H), 6.41 (td, J = 8.2, 2.4 Hz, 1 H), 6.58 (d, J = 7.9 Hz, 1 H), 6.71-6.78 (m, 2 H), 6.86-6.95 (m, 2 H), 7.22-7.35 (m, 2 H), 7.72-7.76 (m, 1 H), 8.56-8.65 (m, 2 H) |
[제제예]
이하 본 화합물을 포함하는 일반적인 제제예를 나타낸다.
1) 정제(150 mg 중)
본 화합물 1 mg
유당 100 mg
옥수수 전분 40 mg
카르복시메틸 셀룰로오스 칼슘 4.5 mg
하이드록시프로필 셀룰로오스 4 mg
스테아르산 마그네슘 0.5 mg
상기 처방의 정제에 코팅제(예를 들면, 하이드록시프로필메틸 셀룰로오스, 마크로콜, 실리콘 수지 등의 통상의 코팅제) 3 mg를 사용하여 코팅을 행하여, 목적으로 하는 정제를 얻을 수 있다. 또한, 본 화합물 및 첨가물의 종류 및/또는 양을 적절하게 변경함으로써, 원하는 정제를 얻을 수 있다.
2) 캡슐제(150 mg 중)
본 화합물 5 mg
유당 135 mg
카르복시메틸 셀룰로오스 칼슘 4.5 mg
하이드록시프로필 셀룰로오스 4 mg
스테아르산 마그네슘 1.5 mg
본 화합물 및 첨가제의 종류 및/또는 양을 적절하게 변경함으로써, 원하는 캡슐제를 얻을 수 있다.
3) 점안제(100 ml 중)
본 화합물 100 mg
염화 나트륨 900 mg
폴리소르베이트 80 500 mg
수산화나트륨 적당량
염산 적당량
멸균 정제수 적당량
본 화합물 및 첨가물의 종류 및/또는 양을 적절하게 변경함으로써, 원하는 점안제를 얻을 수 있다.
[약리 시험]
1.GR 결합 활성 평가 시험
본 화합물의 GR에 대한 결합 활성을 평가하기 위해, 편광형광법에 의한 GR 수용체 경쟁 어세이를 실시하였다. 어세이는 GR 경쟁 어세이 키트(Invitrogen사 제, Cat No.P2816)를 사용하여, 본 키트에 첨부된 프로토콜에 준하여 수행하였다. 이하 그 구체적인 방법을 기재한다.
(시약의 조제)
GR 스크리닝 완충액:10 mM 인산 칼륨(pH 7.4), 20 mM 몰리브덴산 나트륨(Na2MoO4), 0.1 mM 에틸렌 디아민 테트라아세트산(이하, 「EDTA」라고 함), 5 mM 디티오트레이톨(DTT), 0.1 mM 안정화 펩티드 및 2% 디메틸술폭시드의 완충액으로 되도록 조제하였다.
4 x GS1 용액:형광 글루코코르티코이드 리간드인 FluormoneTM GS1를 GR 스크리닝 완충액으로 희석하여, 4 nM의 용액을 조제하였다.
4 x GR용액:재조합 인간 GR를 GR 스크리닝 완충액으로 희석하여, 16 nM의 용액을 조제하였다.
(시험 화합물 용액의 조제)
시험 화합물을 디메틸술폭시드에 용해 후, GR 스크리닝 완충액으로 희석하여, 20 μM의 시험 화합물 용액을 조제하였다.
(시험 방법 및 측정 방법)
1) 384-웰 플레이트에 시험 화합물 용액을 1웰당 10 ㎕씩 주입하고, 이어서, 4 x GS1 용액 및 4 x GR 용액을 1 웰당 5 ㎕씩 첨가하였다.
2) 암소에서 실온으로 2-4시간 인큐베이트 했다.
3) 멀티모드 플레이트 리더 AnalystTM HT(LJL Biosystems사 제)를 사용하고, 블랭크로서, 시험 화합물 용액 및 4 x GS1 용액 대신에 GR 스크리닝 완충액을 포함하는 웰을 사용하여 각 웰의 형광 편광을 측정하였다.
4) 시험 화합물 용액 대신에 GR 스크리닝 완충액을 사용하는 것 이외에는 상기 1∼3)과 같은 조작을 실시하고, 그 결과를 음성 대조군으로 하였다.
5) 시험 화합물 용액 대신에 2 mM 덱사메타손을 사용하는 것 이외에는 상기 1∼3)과 같은 조작을 실시하고, 그 결과를 양성 대조군으로 하였다.
(GR 결합율의 계산식)
GR 결합율(%)은 이하의 식에 의해 산출하였다.
GR 결합율(%) = 100 x [1-(시험 화합물 용액의 형광 편광-양성 대조 용액의 형광 편광)/(음성 대조 용액의 형광 편광-양성 대조 용액의 형광 편광)]
(시험 결과 및 고찰)
시험 결과의 일례로서, 화합물 1-3, 화합물 1-6, 화합물 1-7, 화합물 1-8, 화합물 1-9, 화합물 1-12, 화합물 1-13, 화합물 1-14, 화합물 1-15, 화합물 1-17, 화합물 1-18, 화합물 1-19, 화합물 1-25, 화합물 1-33, 화합물 1-36, 화합물 1-38, 화합물 1-40, 화합물 1-45, 화합물 1-48, 화합물 1-49, 화합물 1-54, 화합물 1-55, 화합물 1-57, 화합물 1-58, 화합물 1-68, 화합물 1-69, 화합물 1-72, 화합물 1-81, 화합물 1-91, 화합물 1-92, 화합물 1-95, 화합물 1-97, 화합물 1-98, 화합물 1-99, 화합물 1-101, 화합물 1-102, 화합물 1-104, 화합물 1-105, 화합물 1-106, 화합물 1-107, 화합물 1-110, 화합물 1-111, 화합물 1-114, 화합물 1-117, 화합물 1-119, 화합물 1-122, 화합물 1-125, 화합물 1-126, 화합물 1-128, 화합물 1-133, 화합물 1-136, 화합물 1-137, 화합물 1-138, 화합물 1-139, 화합물 1-141, 화합물 1-142, 화합물 1-143, 화합물 1-144, 화합물 1-147, 화합물 1-148, 화합물 1-151, 화합물 1-153, 화합물 1-155, 화합물 1-156, 화합물 1-157, 화합물 1-160, 화합물 1-162, 화합물 1-164, 화합물 1-165, 화합물 1-166, 화합물 1-169, 화합물 1-170, 화합물 1-171, 화합물 4-3, 화합물 4-4, 화합물 4-5, 화합물 4-6, 화합물 4-8, 화합물 4-11, 화합물 4-12, 화합물 4-14, 화합물 4-18, 화합물 4-20, 화합물 4-21, 화합물 4-26, 화합물 4-27, 화합물 4-29, 화합물 4-30, 화합물 4-32, 화합물 4-34, 화합물 6-3, 화합물 6-20, 화합물 6-26, 화합물 6-27, 화합물 6-31, 화합물 6-33, 화합물 6-35 또는 화합물 6-37을 시험 화합물로서 사용한 경우의 시험 결과를 이하에 나타낸다.
이들 화합물은 모두 64% 이상의 GR 결합율을 나타내었다.
2.GR 작용제 활성의 평가 시험
본 화합물의 GR 작용제로서의 활성을 평가하기 위해, LPS 자극 후의 사람 각막상피 세포주에 있어서의 IL-6 생성 억제 작용을 검토했다. 샘플 중의 IL-6 생성율의 측정에는 HTRF법(Boehringer-Ingelheim사 제, Cat No.62IL6PEB)를 사용하고, 첨부된 프로토콜에 준하여 실시하였다. 이하 그 구체적인 방법을 기재한다.
(시약의 조제)
LPS 조제액:LPS를 인산 완충 생리 식염액(이하, 「PBS(-)」라고 함)에 용해 후, 배양액으로 희석하여, 1 ㎍/mL LPS 용액을 조제하였다.
(시험 화합물 용액 및 덱사메타손(이하, 「DEX」라고 함) 용액의 조제)
시험 화합물을 디메틸술폭시드(이하, 「DMSO」라고 함)에 용해 후, 배양액으로 희석하여 100 μM의 시험 화합물 용액을 조제하였다. 또한, DEX를 마찬가지로 용해하여 100 μM DEX 용액을 조제하고, DEX의 IL-6 생성 억제율을 측정하여, 효능(%DEX)의 산출에 사용하였다.
(사용 세포 및 배양 방법)
사용 세포:사람 각막상피 세포주(HCE-T)(이화학 연구소)
배양 방법:
1) 서브컨플루언트(subconfluent) 상태까지 증식한 HCE-T를 PBS(-)로 세정하고, 트립신-EDTA 처리에 의해 세포를 박리하였다.
2) SHEM 배지(supplemented hormone epithelial medium: 15% FBS, 5 ㎍/mL 인슐린, 0.1 ㎍/mL 콜레라 독소(choleratoxin), 10 ng/mL 인간 EGF, 40 ㎍/mL 겐타마이신 함유 DMEM/Ham's F12)를 첨가하고, 트립신를 불활성화했다.
3) 상기 현탁액을 회수하고, 1000 rpm으로 5 분간 원심분리하여 세포 침전물을 얻었다.
4) 세포 침전물을 SHEM 배지로 현탁하고, 배양 플라스크에 파종 후, CO2 인큐베이터(온도:37℃, CO2 농도:5%) 내에서 배양했다. 본 발명에 의해, 계대 배양을 계속한 세포를 시험에 사용하였다.
(시험 방법 및 측정 방법)
1) 계대 배양한 HCE-T를 회수하고, 96-웰 배양 플레이트에 세포를 2.0 x 104 cells/0.1 mL/well씩 파종했다.
2) 밤새 배양한 후, 배지를 제거하고, 10% FBS-DMEM/Ham's F12 배지를 80 ㎕/well씩 첨가하였다.
3) 각 시험 화합물 용액을 10 ㎕/well씩 첨가하였다.
4) LPS 용액을 10 ㎕/well씩 첨가하였다.
5) 각 시험 화합물 용액 및 LPS 용액 대신 10% FBS-DMEM/Ham's F12 배지를 첨가한 것을 음성 대조군으로 하였다.
6) 각 시험 화합물 용액 대신 1% DMSO 함유 10% FBS-DMEM/Ham's F12 배지를 10 ㎕/well씩 첨가한 것을 양성 대조군으로 하였다.
7) 4시간의 배양 종료 후, 상청액을 회수하고, 상청액 중에 유리하고 있는 IL-6량을 HTRF 인간 IL-6 키트를 사용하여 측정하였다.
8) 이하의 계산식에 따라 IL-6 생성 억제율을 산출하였다.
(IL-6 생성 억제율의 계산식)
IL-6 생성 억제율(%)은 이하의 식에 의해 산출하였다.
IL-6 생성 억제율(%) = 100 X{1-(각 샘플의 IL-6 생성량-음성 대조군의 IL-6 생성량 평균값)/(양성 대조군의 IL-6 생성량 평균값-음성 대조군의 IL-6 생성량 평균값)} (%)
또한, DEX 처치군을 100으로 했을 때의 IL-6 생성 억제율(효능(%DEX))를 산출하였다.
효능(%DEX) = 100 X{(각 샘플의 IL-6 생성 억제율의 평균)/(DEX 처치군IL-6 생성 억제율의 평균값)}(%)
(시험 결과 및 고찰)
시험 결과의 일례로서, 화합물 1-3, 화합물 1-6, 화합물 1-7, 화합물 1-8, 화합물 1-9, 화합물 1-12, 화합물 1-13, 화합물 1-14, 화합물 1-15, 화합물 1-17, 화합물 1-18, 화합물 1-19, 화합물 1-25, 화합물 1-33, 화합물 1-36, 화합물 1-38, 화합물 1-40, 화합물 1-45, 화합물 1-48, 화합물 1-49, 화합물 1-54, 화합물 1-55, 화합물 1-57, 화합물 1-58, 화합물 1-68, 화합물 1-69, 화합물 1-72, 화합물 1-81, 화합물 1-91, 화합물 1-92, 화합물 1-95, 화합물 1-97, 화합물 1-98, 화합물 1-99, 화합물 1-101, 화합물 1-102, 화합물 1-104, 화합물 1-105, 화합물 1-106, 화합물 1-107, 화합물 1-110, 화합물 1-111, 화합물 1-114, 화합물 1-117, 화합물 1-119, 화합물 1-122, 화합물 1-125, 화합물 1-126, 화합물 1-128, 화합물 1-133, 화합물 1-136, 화합물 1-137, 화합물 1-138, 화합물 1-139, 화합물 1-141, 화합물 1-142, 화합물 1-143, 화합물 1-144, 화합물 1-147, 화합물 1-148, 화합물 1-151, 화합물 1-153, 화합물 1-155, 화합물 1-156, 화합물 1-157, 화합물 1-160, 화합물 1-162, 화합물 1-164, 화합물 1-165, 화합물 1-166, 화합물 1-169, 화합물 1-170, 화합물 1-171, 화합물 4-3, 화합물 4-4, 화합물 4-5, 화합물 4-6, 화합물 4-8, 화합물 4-11, 화합물 4-12, 화합물 4-14, 화합물 4-18, 화합물 4-20, 화합물 4-21, 화합물 4-26, 화합물 4-27, 화합물 4-29, 화합물 4-30, 화합물 4-32, 화합물 4-34, 화합물 6-3, 화합물 6-20, 화합물 6-26, 화합물 6-27, 화합물 6-31, 화합물 6-33, 화합물 6-35 또는 화합물 6-37을 시험 화합물로서 사용한 경우의 IL-6 생성 억제 작용(%DEX)을 표 32에 나타낸다.
화합물 | IL-6 생성 억제율 (%DEX) |
화합물 | IL-6 생성 억제율 (%DEX) |
화합물 1-3 | 76 | 화합물 1-133 | 74 |
화합물 1-6 | 93 | 화합물 1-136 | 89 |
화합물 1-7 | 78 | 화합물 1-137 | 83 |
화합물 1-8 | 94 | 화합물 1-138 | 79 |
화합물 1-9 | 79 | 화합물 1-139 | 104 |
화합물 1-12 | 85 | 화합물 1-141 | 78 |
화합물 1-13 | 94 | 화합물 1-142 | 97 |
화합물 1-14 | 79 | 화합물 1-143 | 96 |
화합물 1-15 | 77 | 화합물 1-144 | 94 |
화합물 1-17 | 84 | 화합물 1-147 | 80 |
화합물 1-18 | 77 | 화합물 1-148 | 86 |
화합물 1-19 | 78 | 화합물 1-151 | 90 |
화합물 1-25 | 83 | 화합물 1-153 | 89 |
화합물 1-33 | 82 | 화합물 1-155 | 83 |
화합물 1-36 | 75 | 화합물 1-156 | 90 |
화합물 1-38 | 75 | 화합물 1-157 | 76 |
화합물 1-40 | 75 | 화합물 1-160 | 88 |
화합물 1-45 | 77 | 화합물 1-162 | 81 |
화합물 1-48 | 73 | 화합물 1-164 | 85 |
화합물 1-49 | 96 | 화합물 1-165 | 93 |
화합물 1-54 | 75 | 화합물 1-166 | 91 |
화합물 1-55 | 76 | 화합물 1-169 | 78 |
화합물 1-57 | 86 | 화합물 1-170 | 77 |
화합물 1-58 | 76 | 화합물 1-171 | 87 |
화합물 1-68 | 72 | 화합물 4-3 | 81 |
화합물 1-69 | 72 | 화합물 4-4 | 89 |
화합물 1-72 | 82 | 화합물 4-5 | 90 |
화합물 1-81 | 76 | 화합물 4-6 | 82 |
화합물 1-91 | 92 | 화합물 4-8 | 78 |
화합물 1-92 | 79 | 화합물 4-11 | 75 |
화합물 1-95 | 87 | 화합물 4-12 | 77 |
화합물 1-97 | 81 | 화합물 4-14 | 80 |
화합물 1-98 | 78 | 화합물 4-18 | 89 |
화합물 1-99 | 89 | 화합물 4-20 | 75 |
화합물 1-101 | 81 | 화합물 4-21 | 82 |
화합물 1-102 | 99 | 화합물 4-26 | 77 |
화합물 1-104 | 84 | 화합물 4-27 | 101 |
화합물 1-105 | 97 | 화합물 4-29 | 92 |
화합물 1-106 | 82 | 화합물 4-30 | 93 |
화합물 1-107 | 85 | 화합물 4-32 | 77 |
화합물 1-110 | 83 | 화합물 4-34 | 86 |
화합물 1-111 | 81 | 화합물 6-3 | 83 |
화합물 1-114 | 87 | 화합물 6-20 | 79 |
화합물 1-117 | 95 | 화합물 6-26 | 84 |
화합물 1-119 | 75 | 화합물 6-27 | 94 |
화합물 1-122 | 89 | 화합물 6-31 | 86 |
화합물 1-125 | 81 | 화합물 6-33 | 78 |
화합물 1-126 | 81 | 화합물 6-35 | 87 |
화합물 1-128 | 79 | 화합물 6-37 | 85 |
표 32에 나타난 바와 같이, 본 화합물은 우수한 IL-6 생성 억제 작용을 나타내었다. 따라서, 본 화합물은 GR 작용제로서 사용할 수 있어, 염증성 질환, 특히 전안부 또는 후안부 염증성 질환 및 염증성 골·관절 질환의 예방 또는 치료제로서 유용하다.
3.알레르기성 결막염 모델에 있어서의 혈관 투과성 항진 억제 효과
본 화합물의 항알레르기-작용을 평가하기 위해, 마우스의 알레르기성 결막염 모델에 대한 본 화합물의 혈관 투과성 항진 억제 효과를 검토했다. 본 효과는 기제 투여군(대조군)의 색소 누출량과 시험 화합물 투여군의 색소 누출량으로부터 산출하였다.
(시험 화합물 현탁용액의 조제)
시험 화합물에 0.5% 폴리소르베이트 80/생리식염수를 가하여, 1%(W/V)의 시험 화합물 현탁액을 조제하였다.
(알레르기성 결막염 모델의 제작 및 평가 방법)
1) 수산화 알루미늄겔 흡착 오브알부민(20 ㎍/mL)을 생리식염수에 용해하고, 6주령의 웅성 BALB/c계 마우스의 복강 내에 500 ㎕씩 주사하고, 능동 감작을 실시하였다.
2) 감작 6일째에 재차 수산화 알루미늄겔 흡착 오브알부민(20 ㎍/mL)을 500 ㎕씩 주사하고 추가 감작을 실시하였다.
3) 첫 회 감작으로부터 11일째, 12일째, 13일째, 14일째 및 15일째에, 오브알부민 15%(W/V) 함유 50% 글리세롤 용액을 2 ㎕씩 마우스의 우안에 점안 투여하여, 알레르기성 결막염을 야기시켰다.
4) 감작 15일째 오브알부민을 점안 투여하기 3시간 전, 1시간 전 및 15분 전(합계 3회)에, 시험 화합물 현탁용액을, 상기 마우스의 우안에 각각 2 ㎕씩 점안 투여했다. 그리고, 기제 투여군(대조군)에는 시험 화합물 현탁용액 대신에 0.5% 폴리소르베이트 80/생리식염수를 사용하였다.
5) 감작 15일째 오브알부민을 점안하기 직전에 0.1% Evans Blue 용액을 마우스의 꼬리정맥으로 주사하고, 오브알부민을 점안한지 30분 후에 색소 누출 부위에서 있는 마우스의 우안 주변을 적출하고, 색소 추출액에서 색소를 추출했다. 그 다음에, 추출한 색소의 흡광도를 측정하고, 얻어진 흡광도로 색소 누출량을 산출하고, 계산식 1에 의해 알레르기성 결막염에 따른 혈관 투과성 항진에 대한 시험 화합물 투여군의 혈관 투과성 항진 억제율을 산출하였다.
(계산식 1)
시험 화합물 투여군의 혈관 투과성 항진 억제율(%) = (1-Ax/Ao) x 100
Ao: 기제 투여군(대조군)의 색소 누출량
Ax: 시험 화합물 투여군의 색소 누출량
(시험 결과 및 고찰)
시험 결과의 일례로서, 화합물 1-7, 화합물 1-12, 화합물 1-13, 화합물 1-18, 화합물 1-72, 화합물 1-97, 화합물 1-102, 화합물 1-105, 화합물 1-136, 화합물 1-137, 화합물 1-138, 화합물 1-139 또는 화합물 4-18을 시험 화합물로서 사용한 경우의 혈관 투과성 항진 억제율(%)을 표 33에 나타내었다.
화합물 | 혈관 투과성 항진 억제율(%) |
화합물 1-7 | 28 |
화합물 1-12 | 17 |
화합물 1-13 | 24 |
화합물 1-18 | 30 |
화합물 1-72 | 21 |
화합물 1-97 | 21 |
화합물 1-102 | 16 |
화합물 1-105 | 18 |
화합물 1-136 | 15 |
화합물 1-137 | 26 |
화합물 1-138 | 16 |
화합물 1-139 | 15 |
화합물 4-18 | 21 |
(상기 수치는 5-6 개체, 5-6개 눈의 평균값)
표 33에 나타난 바와 같이, 본 화합물은 혈관 투과성 항진 저해 효과를 가진다. 따라서, 본 화합물은 전안부 염증성 질환의 예방 또는 치료제로서 유용하다.
4.맥락막 혈관 신생 저해 효과의 평가 시험
약물의 맥락막 혈관 신생 저해 효과를 평가하는 일반적인 방법의 하나로서, 래트 맥락막 혈관 신생 모델을 사용한 신생 혈관 발현 시험이 알려져 있고, 그 시험 방법이 Graefe's Arch. Cli. Exp. Ophthalmol., 235,313-319(1997)에 보고되어 있다. 따라서 상기 문헌에 기재된 방법에 준하여, 본 화합물의 신생 혈관 발현 시험을 행하고, 기제 투여군(대조군)의 신생 혈관 발현율에 대한 본 화합물 투여군의 신생 혈관 발현율의 비율을 산출하고, 이것을 지표로 본 화합물의 맥락막 혈관 신생 저해 효과를 평가했다.
(시험 화합물 현탁용액의 조제)
점안 투여의 경우에는, 시험 화합물에 0.5% 폴리소르베이트 80/생리식염수를 가하여 현탁하고, 1 %(W/V)의 시험 화합물 현탁액을 조제하였다. 결막하 투여의 경우에는, 시험 화합물에 0.5% 경화 피마자유/생리식염수를 가하여 현탁하고, 20 mg/mL의 시험 화합물 현탁액을 조제하였다.
(레이저 유발 래트 맥락막 혈관 신생 모델의 제작)
1) 래트(Brown Norway 웅성 래트, 7-8주령, 체중 140-240 g)에 5% 염산 케타민 주사액과 2% 염산 자일라진 주사액의 7 : 1 혼합액(1 mL/kg)을 근육내 투여하고, 전신 마취했다.
2) 트로피카미드ㆍ염산 페닐에프린 점안액(상품명:Mydrin P)을 점안해 동공을 확장시킨 후, 크립톤 레이저 광 응고 장치를 사용하여, 래트의 브르크막(bruch's membrane)을 광 응고하였다.
레이저 조사는, 안저 뒤 국부의 굵은 망막혈관을 피해 그 초점을 망막심층에 맞추고, 한 눈당 8-9개소에 실시하였다. 광 응고의 조건은, 스폿 사이즈 100㎛, 출력 100 mM, 응고 시간 0.1초로 하였다.
3) 광 응고 후, 안저 촬영을 행하고, 광 응고(레이저 조사) 부위를 확인하였다.
(시험 방법 및 측정 방법)
1) 점안 투여의 경우에는, 레이저 조사일(1일째)로부터 8일째까지, 시험 화합물 현탁용액을 1일 4회, 연일 점안 투여했다. 결막하 투여의 경우에는, 레이저 조사 직후에 1회 50㎕를 주사했다.
2) 기제 투여군(대조군)으로서 시험 화합물 현탁용액 대신에, 0.5% 폴리소르베이트 80/생리 식염액 또는 0.5% 경화 피마자유/생리식염수를 사용하는 것을 제외하고는 1)과 같은 방법으로 시험을 행하고, 그 결과를 대조군으로 하였다.
(평가 방법)
1) 광 응고 7일째에 10% 플루오레세인 수용액 0.1 mL를 래트의 꼬리 정맥으로 주입하여, 형광 안저조영을 실시하였다.
2) 이어서, 형광 안저조영으로 형광의 누출이 검출되지 않은 스폿을 음성, 형광 누출이 검출된 스폿을 양성으로 하고, 약간의 형광 누출이 검출된 광 응고 부위가 2개소 존재하는 경우에는 양성으로 판단하였다.
3) 계산식 1에 따라 신생 혈관 발현율을 산출하였다. 각 투여군의 신생 혈관 발현율로부터 계산식 2에 따라 기제 투여군에 대한 시험 화합물 투여군의 신생 혈관 발현율의 비율을 산출하였다.
(계산식 1)
신생 혈관 발현율(%) = (양성 광 응고 부위 수/전체 광 응고 부위 수) x 100
(계산식 2)
시험 화합물 투여군의 신생 혈관 억제율(%) = (1-Ax/Ao) x 100
Ao: 기제 투여군(대조군)의 신생 혈관 발현율
Ax: 시험 화합물 투여군의 신생 혈관 발현율
(시험 결과 및 고찰)
시험 결과의 일례로서, 화합물 1-9, 화합물 1-12, 화합물 1―13, 화합물 1-14, 화합물 1-17, 화합물 1-19, 화합물 1-25, 화합물 1-33, 화합물 1―49, 화합물 1-72, 화합물 4-5, 화합물 4-8, 화합물 4-18, 화합물 6-3, 화합물 6―31 또는 화합물 6-35를 시험 화합물로서 사용한 경우의 신생 혈관 억제율(%)을 표 34에 나타낸다.
화합물 | 신생 혈관 억제율(%) |
화합물 1-9 | 31 |
화합물 1-12 | 37 |
화합물 1-13 | 38 |
화합물 1-14 | 46 |
화합물 1-17 | 35 |
화합물 1-19 | 30 |
화합물 1-25 | 50 |
화합물 1-33 | 29 |
화합물 1-49 | 23 |
화합물 1-72 | 28 |
화합물 4-5 | 38 |
화합물 4-8 | 26 |
화합물 4-18 | 35 |
화합물 6-3 | 38 |
화합물 6-31 | 45 |
화합물 6-35 | 26 |
(상기 수치는 4 개체, 7-8개 눈의 평균값)
표 34에 나타난 바와 같이, 본 화합물은 기제에 비해 신생 혈관을 억제하고, 맥락막 혈관 신생 저해 효과를 가진다. 따라서, 본 화합물은 후안부 염증성 질환의 예방 또는 치료제로서 유용하다.
5.각막 장해의 치유 효력 시험
약물의 건성안을 수반하는 각막 장해의 개선 효과를 검토하기 위해, 웅성 SD래트를 사용하고, Fujihara 등의 방법(Invest. Ophthalmol. Vis. Sci 42(1):96-100 (2001))에 따라 각막 장해 모델을 제작하였다. 각막 장해 모델 제작 후, 무라카미 등의 방법(Journal of the eye 21(1):87-90(2004))에 따라 각막 장해의 개선율을 판정하였다.
(시험 화합물 현탁용액의 조제)
시험 화합물에 폴리소르베이트 80이나 일반적인 첨가제를 포함하는 기제를 가하여, 0.03 %(W/V)의 시험 화합물 현탁액을 조제하였다.
(건성안에 따른 각막 장해 모델의 제작 및 평가 방법)
1) 웅성 SD래트를 사용하고, 솜노펜틸을 투여해 전신 마취를 행한 후, 안와외 눈물샘을 적출하여, 2개월에 걸쳐 각막 장해를 유발시켰다.
2) 시험 화합물 현탁액을 양 눈에 1일 6회, 14일간 점안했다. 그리고, 대조군에는 기제를 동일하게 점안했다.
3) 점안 개시 14일 후, 각막의 장해 부분을 플르오레세인으로 염색했다. 각막의 상부, 중간부 및 하부의 각각에 대한, 플르오레세인에 의한 염색의 정도를 하기 기준에 따라 스코어 판정하고, 이들 스코어의 합계의 평균값을 산출하였다. 그리고, 0, 1, 2, 3의 각 스코어 사이에 중간값으로서 0.5를 설정하였다.
《판정 기준》
0:염색되어 있지 않음.
1:염색이 드문드문하고, 각 점형의 염색 부분이 흩어져 있음.
2:염색이 중정도이며, 점형의 염색 부분의 일부가 인접하고 있음.
3:염색이 조밀하고, 각 점형의 염색 부분은 인접하고 있음.
(계산식)
시험 화합물 투여군의 개선율(%) = (Ao-Ax)/(Ao-An) x 100
Ao: 기제 투여군(대조군)의 각막 장해 스코어 평균값
Ax: 시험 화합물 투여군의 각막 장해 스코어 평균값
An: 정상 래트의 각막 장해 스코어 평균값
(시험 결과 및 고찰)
시험 결과의 일례로서, 화합물 1-12, 화합물 1―13, 화합물 1-72 또는 화합물 4-18을 시험 화합물로서 사용한 경우의 각막 장해 개선율(%)을 표 35에 나타내었다.
화합물 | 각막 장해 개선율(%) |
화합물 1-12 | 69 |
화합물 1-13 | 61 |
화합물 1-72 | 67 |
화합물 4-18 | 56 |
(상기 수치는 4 개체, 8개 눈의 평균값)
표 35에 나타난 바와 같이, 본 화합물은 기제에 비해 각막 장해 개선 효과를 가진다. 따라서, 본 화합물은 건성안 등을 수반하는 각막 장해의 예방 또는 치료제로서 유용하다.
6.아토피성 피부염 모델에 있어서의 혈관 투과성 항진 억제 작용
본 화합물의 아토피성 피부염에 대한 작용을 평가하기 위해, 마우스의 아토피성 피부염 모델로서 보고되어 있는 Nagai 등의 방법(J. Pharmacol. Exp. Ther., 283: 321-327 (1997))에 수정을 가한 방법으로 혈관 투과성 항진 억제 효과를 검토했다. 그리고, 본 효과는 기제 투여군(대조군)의 색소 누출량과 시험 화합물 투여군의 색소 누출량으로부터 산출하였다.
(시험 화합물 연고의 조제)
시험 화합물에 백색 바셀린을 가하여, 1 %(W/W)의 시험 화합물 연고를 조제하였다.
(아토피성 피부염 모델의 제작 및 평가 방법)
1) 주 1회, 4주간에 걸쳐 5회, 마우스의 양귓바퀴의 양면에 0.15% DNFB 용액 25 ㎕를 도포하여 피부염을 야기했다.
2) 시험 화합물 연고를 첫회 DNFB 도포의 전날부터 5회째 도포 전날까지, 주 5회, 총 21회, 마우스 귓바퀴의 한면당 25 ㎕씩 양귓바퀴의 양면에 도포함으로써 투여했다. 그리고, 기제 투여군(대조군)에는 백색 바셀린을 마찬가지로 도포함으로써 투여했다.
3) 5회째의 DNFB 용액 도포 직후, 마우스에 0.2% Evans Blue 용액을 꼬리 정맥으로 주사하고, 색소를 꼬리 정맥에 주사한지 2시간 후에, 색소 누출 부위가 있는 마우스의 귓바퀴를 적출하고, 색소 추출액에서 색소를 추출했다. 그 다음에, 추출한 색소의 흡광도를 측정하고, 얻어진 흡광도로부터 누출 색소량을 산출하고, 계산식 1에 의해 아토피성 피부염에 따른 혈관 투과성 항진에 대한 시험 화합물 투여군의 혈관 투과성 항진 억제율을 산출하였다.
(계산식 1)
시험 화합물 투여군의 혈관 투과성 항진 억제율(%) = (1-Ax/Ao) x 100
Ao: 기제 투여군(대조군)의 색소 누출량
Ax: 시험 화합물 투여군의 색소 누출량
(시험 결과 및 고찰)
시험 결과의 일례로서, 화합물 1-12, 화합물 1―13, 화합물 1-72 또는 화합물 4-18을 시험 화합물로서 사용한 경우의 혈관 투과성 항진 억제율(%)을 표 36에 나타낸다.
화합물 | 혈관 투과성 항진 억제율(%) |
화합물 1-12 | 22 |
화합물 1-13 | 13 |
화합물 1-72 | 15 |
화합물 4-18 | 30 |
(상기 수치는 6개체, 12개 귀의 평균값)
표 36에 나타난 바와 같이, 본 화합물은 기제에 비해 아토피 피부염에 수반되는 혈관 투과성 항진의 저해 효과를 가진다. 따라서, 본 화합물은 아토피성 피부염 등의 피부염의 예방 또는 치료제로서 유용하다.
본 발명은 글루코코르티코이드 수용체 작용제, 상기 글루코코르티코이드 수용체 작용제를 유효 성분으로서 함유하는 의약 조성물, 상기 글루코코르티코이드 수용체 작용제를 유효 성분으로서 함유하는 염증성 질환의 예방 또는 치료제 및 상기 글루코코르티코이드 수용체 작용제를 유효 성분으로서 함유하는 안염증성 질환 또는 피부염의 예방 또는 치료제로서 유용하고, 특히 각막염, 각결막염, 결막염, 안검염, 안구 건조 증후군(「건성안」이라고도 함), 알레르기성 결막염, 앞부분 포도막염, 전안부의 수술 후 염증, 눈 조직 이식 거부반응에 의한 염증 등의 전안부 염증성 질환 및/또는 연령관련 황반변성(초기 연령관련 황반변성, 위축형 연령관련 황반변성 및/또는 삼출형 연령관련 황반변성), 당뇨성 망막증, 당뇨성 황반부종, 혈관신생 황반증, 돌발성 황반상막, 증식성 유리체 망막증, 망막색소 변성증, 망막 중심 정맥 폐색증, 망막 중심 동맥 폐색증, 망막정맥 분지 폐색증, 망막동맥 분지 폐색증, 망막박리나 외상에 의한 염증이나 변성, 후안부의 수술 후 염증, 망막염, 포도막염, 공막염, 시신경염 등의 후안부 염증성 질환의 예방 또는 치료제로서 유용하다.
Claims (35)
- 하기 일반식 (1)로 표시되는 화합물 또는 그 염을 포함하는 글루코코르티코이드 수용체 작용제:
[상기 식에서, R1은 하기 일반식 (2a), (3a), (4a) 또는 (5a)를 나타내고;
R2는 -(CO)-R8, -(CO)O-R9, -(SO)-R10, -(SO2)-R11 또는 -(CO)NR12R13을 나타내고;
R2-O-는, 벤젠환 A의 4 또는 5번 위치에서 치환되고;
R3는 저급 알킬기를 나타내고;
R4, R5, R6 또는 R7은, 할로겐 원자, 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 알키닐기, 저급 알콕시기, 니트로기 또는 포르밀기를 나타내고;
m, n, p 또는 q는, 0, 1 또는 2를 나타내고;
m, n, p 또는 q가 2를 나타내는 경우, 각 R4, R5, R6 또는 R7은 동일 또는 상이해도 되고;
R8, R9, R10 또는 R11은, 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 시클로알킬기, 치환기를 가질 수 있는 아릴기 또는 치환기를 가질 수 있는 복소환기를 나타내고;
R12 및 R13은 동일 또는 상이해도 되며, 수소 원자, 치환기를 가질 수 있는 저급 알킬기, 치환기를 가질 수 있는 아릴기 또는 복소환기를 나타냄]. - 제1항에 있어서,
상기 일반식 (1)에서,
R1이 하기 일반식 (2a), (3a), (4a) 또는 (5a)를 나타내고;
R2가 -(CO)-R8, -(CO)O-R9, -(SO)-R10, -(SO2)-R11 또는 -(CO)NR12R13을 나타내고;
R2-O-가, 벤젠환 A의 4 또는 5번 위치에서 치환되고;
R3가 저급 알킬기를 나타내고;
R4가 할로겐 원자, 저급 알킬기, 저급 알콕시기 또는 니트로기를 나타내고;
R5가 할로겐 원자, 저급 알킬기 또는 저급 알콕시기를 나타내고;
R6가 할로겐 원자, 저급 알킬기 또는 저급 알콕시기를 나타내고;
R7가 할로겐 원자 또는 저급 알킬기를 나타내고;
m, n 또는 p가 1 또는 2를 나타내고;
m, n 또는 p가 2를 나타낸 경우, 각 R4, R5 또는 R6는 동일 또는 상이해도 되고;
q가 1을 나타내고;
R8이 치환기를 가질 수 있는 저급 알킬기, 저급 알케닐기, 저급 시클로알킬기, 치환기를 가질 수 있는 아릴기 또는 치환기를 가질 수 있는 복소환기를 나타내고;
R9이 치환기를 가질 수 있는 저급 알킬기 또는 치환기를 가질 수 있는 아릴기를 나타내고;
R10 또는 R11이, 치환기를 가질 수 있는 저급 알킬기 또는 저급 시클로알킬기를 나타내고;
R12 및 R13이 동일 또는 상이해도 되며, 수소 원자, 치환기를 가질 수 있는 저급 알킬기, 치환기를 가질 수 있는 아릴기 또는 복소환기를 나타내는 글루코코르티코이드 수용체 작용제. - 제1항 또는 제2항에 있어서,
상기 일반식 (1)에서,
R2가 -(CO)-R8, -(CO)O-R9, -(SO2)-R11 또는 -(CO)NR12R13을 나타내는 글루코코르티코이드 수용체 작용제. - 제5항에 있어서,
상기 일반식 (1)에서,
R2가 -(CO)-R8 또는 -(SO2)-R11를 나타내는 글루코코르티코이드 수용체 작용제. - 제6항에 있어서,
상기 일반식 (1)에서,
R2가 -(CO)-R8을 나타내는 글루코코르티코이드 수용체 작용제. - 제1항 또는 제2항에 있어서,
상기 일반식 (1)에서,
R3가 메틸기를 나타내는 글루코코르티코이드 수용체 작용제. - 제1항 또는 제2항에 있어서,
상기 일반식 (1)에서,
R2-O-가 벤젠환 A의 4번 위치에서 치환되는 글루코코르티코이드 수용체 작용제. - ·6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-부틸릴옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소부틸릴옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-페닐아세톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[5-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-5-프로피오닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-5-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-아세톡시벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(5-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-t-부틸카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로피리딘-4-일카르보닐옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[4-(3-플루오르피리딘-4-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시-5-니트로페녹시메틸)-6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-벤조일옥시-2-메톡시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-플루오르-2-메틸페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-[2-메톡시-4-(티오펜-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3-메톡시카르보닐벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(6-메틸피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(4-메틸벤조일옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메톡시벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-클로로벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-벤조일옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(티오펜-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(퓨란-3-일카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸티오벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메틸피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(티아졸-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(피리딘-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(4-메톡시벤조일옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[2-메톡시-4-(피리딘-3-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-브로모티오펜-2-일카르보닐옥시메틸)-6-[4-(퓨란-2-일카르보닐옥시)-2-메톡시페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-이소프로필카르보닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(2-아세톡시벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-메톡시피리딘-3-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-플루오르벤조일옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(2-니트로벤조일옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3-메틸퓨란-2-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-(4-이소프로필설포닐옥시-2-메톡시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-부틸설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(2-메톡시-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(2-메톡시페닐아미노메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(2-메톡시-4-메틸설포닐옥시페닐)-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페닐아미노메틸)-6-(2-메톡시-4-프로필설포닐옥시페닐)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(3,3,3-트리플루오르프로필설포닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(2-메톡시-4-프로필설포닐옥시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-이소프로필설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로펜틸술포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-에틸설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-시클로프로필설포닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-[N-(2-디메틸아미노에틸)-N-에틸아미노카르보닐옥시]-2-메톡시페닐]-5-(5-플루오르-2-메틸페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[4-(4-클로로페닐아미노카르보닐옥시)-2-메톡시페닐]-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·5-(5-플루오르-2-메틸페녹시메틸)-6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(2-메틸-5-니트로페녹시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린,
·6-[2-메톡시-4-(모르폴린-4-일카르보닐옥시)페닐]-5-(2-메톡시페닐아미노메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린, 및
·6-(4-디메틸아미노카르보닐옥시-2-메톡시페닐)-5-(5-메틸티오펜-2-일카르보닐옥시메틸)-2,2,4-트리메틸-1,2-디하이드로퀴놀린으로 이루어지는 군으로부터 선택되는 화합물 또는 그 염을 포함하는 글루코코르티코이드 수용체 작용제. - 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상을 유효 성분으로서 함유하는 의약 조성물.
- 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상을 유효 성분으로서 함유하는 염증성 질환 또는 면역 질환의 예방 또는 치료제.
- 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상을 유효 성분으로서 함유하는 안염증성 질환 또는 피부염의 예방 또는 치료제.
- 제13항에 있어서,
상기 안염증성 질환이 전안부 염증성 질환인 예방 또는 치료제. - 제14항에 있어서,
상기 전안부 염증성 질환이, 안구 건조 증후군 또는 알레르기성 결막염인 예방 또는 치료제. - 제13항에 있어서,
상기 안염증성 질환이 후안부 염증성 질환인 예방 또는 치료제. - 제16항에 있어서,
상기 후안부 염증성 질환이, 연령관련 황반변성, 당뇨성 망막증 또는 당뇨성 황반부종인 예방 또는 치료제. - 제13항에 있어서,
상기 피부염이 아토피성 피부염인 예방 또는 치료제. - 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상을 유효 성분으로서 함유하는 자가면역질환의 예방 또는 치료제.
- 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상의 약리학적 유효량을 환자에게 투여하는 것을 포함하는 염증성 질환 또는 면역 질환의 예방 또는 치료 방법.
- 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상의 약리학적 유효량을 환자에게 투여하는 것을 포함하는 안염증성 질환 또는 피부염의 예방 또는 치료 방법.
- 제21항에 있어서,
상기 안염증성 질환이 전안부 염증성 질환인 예방 또는 치료 방법. - 제22항에 있어서,
상기 전안부 염증성 질환이, 안구 건조 증후군 또는 알레르기성 결막염인 예방 또는 치료 방법. - 제21항에 있어서,
상기 안염증성 질환이 후안부 염증성 질환인 예방 또는 치료 방법. - 제24항에 있어서,
상기 후안부 염증성 질환이, 연령관련 황반변성, 당뇨성 망막증 또는 당뇨성 황반부종인 예방 또는 치료 방법. - 제21항에 있어서,
상기 피부염이 아토피성 피부염인 예방 또는 치료 방법. - 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상의 약리학적 유효량을 환자에게 투여하는 것을 포함하는 자가면역질환의 예방 또는 치료 방법.
- 염증성 질환 또는 면역 질환의 예방 또는 치료 방법에 사용하기 위한, 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상.
- 안염증성 질환 또는 피부염의 예방 또는 치료 방법에 사용하기 위한, 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상.
- 제29항에 있어서,
상기 안염증성 질환이 전안부 염증성 질환인 글루코코르티코이드 수용체 작용제 중 하나 이상. - 제30항에 있어서,
상기 전안부 염증성 질환이, 안구 건조 증후군 또는 알레르기성 결막염인 글루코코르티코이드 수용체 작용제 중 하나 이상. - 제29항에 있어서,
상기 안염증성 질환이 후안부 염증성 질환인 글루코코르티코이드 수용체 작용제 중 하나 이상. - 제32항에 있어서,
상기 후안부 염증성 질환이, 연령관련 황반변성, 당뇨성 망막증 또는 당뇨성 황반부종인 글루코코르티코이드 수용체 작용제 중 하나 이상. - 제29항에 있어서,
상기 피부염이 아토피성 피부염인 글루코코르티코이드 수용체 작용제 중 하나 이상. - 자가면역질환의 예방 또는 치료 방법에 사용하기 위한 제1항 내지 제10항 중 어느 한 항에 기재된 글루코코르티코이드 수용체 작용제 중 하나 이상.
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JP2008124714 | 2008-05-12 | ||
JPJP-P-2008-124714 | 2008-05-12 | ||
PCT/JP2009/058801 WO2009139361A1 (ja) | 2008-05-12 | 2009-05-12 | 置換オキシ基を有する2,2,4-トリメチル-6-フェニル-1,2-ジヒドロキノリン誘導体からなるグルココルチコイド受容体アゴニスト |
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KR1020107027931A KR20110010634A (ko) | 2008-05-12 | 2009-05-12 | 치환 옥시기를 가지는 2,2,4-트리메틸-6-페닐-1,2-디하이드로퀴놀린 유도체를 포함하는 글루코코르티코이드 수용체 작용제 |
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EP (1) | EP2319835B1 (ko) |
JP (1) | JP5635743B2 (ko) |
KR (1) | KR20110010634A (ko) |
CN (2) | CN102089283B (ko) |
AU (1) | AU2009247250B2 (ko) |
BR (1) | BRPI0912171B8 (ko) |
CA (1) | CA2724055C (ko) |
EA (1) | EA019091B1 (ko) |
ES (1) | ES2574987T3 (ko) |
GE (1) | GEP20146061B (ko) |
MX (1) | MX2010012303A (ko) |
MY (1) | MY158747A (ko) |
TW (1) | TWI510240B (ko) |
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WO (1) | WO2009139361A1 (ko) |
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KR20090086539A (ko) | 2006-11-14 | 2009-08-13 | 산텐 세이야꾸 가부시키가이샤 | (치환 페닐 또는 치환 복소환) 카르보닐옥시 저급 알킬기와 에스테르 구조를 도입한 페닐기를 치환기로서 갖는 신규 1,2-디히드로퀴놀린 유도체 |
WO2012108455A1 (ja) * | 2011-02-09 | 2012-08-16 | 参天製薬株式会社 | 3-ヒドロキシ-6H-ベンゾ[c]クロメン-6-オン誘導体およびその製造方法 |
WO2013108921A1 (ja) * | 2012-01-20 | 2013-07-25 | 参天製薬株式会社 | 1,2-ジヒドロキノリン誘導体またはその塩の工業的製造方法およびその製造中間体 |
WO2014156220A1 (ja) * | 2013-03-28 | 2014-10-02 | アイシン精機株式会社 | 周辺監視装置、及びプログラム |
CN107922356A (zh) | 2015-08-25 | 2018-04-17 | 参天制药株式会社 | [4‑(1,3,3‑三甲基‑2‑氧代‑3,4‑二氢‑1h‑喹喔啉‑7‑基)苯氧基]乙基氧基化合物或其盐 |
KR102619458B1 (ko) | 2017-06-16 | 2023-12-29 | 학교법인 도시샤 | mTOR 인히비터를 포함하는, 눈의 증상, 장해 또는 질환을 치료 또는 예방하기 위한 의약 및 그 응용 |
EP3639855A4 (en) | 2017-06-16 | 2021-03-17 | The Doshisha | COMPOUNDS HAVING CASPASE INHIBITORING ACTIVITY, PHARMACEUTICAL AGENT CONTAINING THEM FOR THE TREATMENT OR PREVENTION OF SYMPTOMS, DISORDERS OR DISEASES OF CORNEAL ENDOTHELIUM, AND APPLICATION OF SUCH PHARMACEUTICAL AGENT |
KR101933217B1 (ko) | 2017-12-28 | 2018-12-27 | (주) 에빅스젠 | 피부 염증 억제용 펩티드 및 이를 포함하는 피부 염증 예방 또는 치료용 조성물 |
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US5696133A (en) * | 1994-12-22 | 1997-12-09 | Ligand Pharmaceuticals Incorporated | Steroid receptor modulator compounds and methods |
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US6696459B1 (en) * | 1994-12-22 | 2004-02-24 | Ligand Pharmaceuticals Inc. | Steroid receptor modulator compounds and methods |
EP1201660B1 (en) | 2000-10-30 | 2005-08-31 | Pfizer Products Inc. | Glucocorticoid receptor modulators |
RU2315041C2 (ru) * | 2002-04-30 | 2008-01-20 | ЮСиБи, С.А. | Производные 2,6-хинолинила и 2,6-нафтила, фармацевтические композиции на их основе, их применение в качестве ингибиторов vla-4 и промежуточные соединения |
AU2003259747A1 (en) * | 2002-08-21 | 2004-03-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted hihydroquinolines as glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
BRPI0513119A (pt) * | 2004-07-14 | 2008-04-29 | Ligand Pharm Inc | compostos e métodos modulares de receptores intracelulares |
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KR20090086539A (ko) | 2006-11-14 | 2009-08-13 | 산텐 세이야꾸 가부시키가이샤 | (치환 페닐 또는 치환 복소환) 카르보닐옥시 저급 알킬기와 에스테르 구조를 도입한 페닐기를 치환기로서 갖는 신규 1,2-디히드로퀴놀린 유도체 |
WO2008111632A1 (ja) * | 2007-03-13 | 2008-09-18 | Santen Pharmaceutical Co., Ltd. | 2,2,4-トリメチル-6-フェニル-1,2-ジヒドロキノリン誘導体からなるグルココルチコイド受容体アゴニスト |
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TW200950781A (en) | 2009-12-16 |
CA2724055A1 (en) | 2009-11-19 |
CN102089283B (zh) | 2015-11-25 |
UA102101C2 (ru) | 2013-06-10 |
EA019091B1 (ru) | 2014-01-30 |
CN105395550A (zh) | 2016-03-16 |
EP2319835B1 (en) | 2016-04-13 |
AU2009247250B2 (en) | 2014-04-10 |
ES2574987T3 (es) | 2016-06-23 |
CA2724055C (en) | 2016-08-02 |
WO2009139361A1 (ja) | 2009-11-19 |
TWI510240B (zh) | 2015-12-01 |
EP2319835A4 (en) | 2011-12-28 |
MY158747A (en) | 2016-11-15 |
BRPI0912171B1 (pt) | 2020-11-03 |
MX2010012303A (es) | 2011-03-30 |
EP2319835A1 (en) | 2011-05-11 |
JP2009298775A (ja) | 2009-12-24 |
US8426406B2 (en) | 2013-04-23 |
US20110118260A1 (en) | 2011-05-19 |
EA201071296A1 (ru) | 2011-06-30 |
BRPI0912171A2 (pt) | 2017-10-31 |
CN102089283A (zh) | 2011-06-08 |
BRPI0912171A8 (pt) | 2017-12-12 |
AU2009247250A1 (en) | 2009-11-19 |
BRPI0912171B8 (pt) | 2021-05-25 |
GEP20146061B (en) | 2014-03-25 |
CN105395550B (zh) | 2018-07-17 |
JP5635743B2 (ja) | 2014-12-03 |
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