KR100357411B1 - 테트라시클릭유도체,제조방법및용도 - Google Patents
테트라시클릭유도체,제조방법및용도 Download PDFInfo
- Publication number
- KR100357411B1 KR100357411B1 KR1019960703922A KR19960703922A KR100357411B1 KR 100357411 B1 KR100357411 B1 KR 100357411B1 KR 1019960703922 A KR1019960703922 A KR 1019960703922A KR 19960703922 A KR19960703922 A KR 19960703922A KR 100357411 B1 KR100357411 B1 KR 100357411B1
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- indole
- pyrido
- pyrazino
- dione
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 269
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 79
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 17
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 15
- 239000012453 solvate Substances 0.000 claims abstract description 15
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 7
- 229930192474 thiophene Natural products 0.000 claims abstract description 7
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 239000011593 sulfur Substances 0.000 claims abstract description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 170
- 239000000203 mixture Substances 0.000 claims description 53
- -1 3,4-methylenedioxyphenyl Chemical group 0.000 claims description 44
- 230000002829 reductive effect Effects 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- FFCZQVKVWGGQFB-UHFFFAOYSA-N 9h-pyrido[3,4-b]indole-1,4-dione Chemical compound N1C2=CC=CC=C2C2=C1C(=O)N=CC2=O FFCZQVKVWGGQFB-UHFFFAOYSA-N 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 206010002383 Angina Pectoris Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
- 208000010412 Glaucoma Diseases 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 201000009961 allergic asthma Diseases 0.000 claims description 6
- 201000010105 allergic rhinitis Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 206010006451 bronchitis Diseases 0.000 claims description 6
- 208000023819 chronic asthma Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
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- 201000006370 kidney failure Diseases 0.000 claims description 6
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 6
- 208000019553 vascular disease Diseases 0.000 claims description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
- 150000001555 benzenes Chemical class 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 230000004899 motility Effects 0.000 claims description 5
- WOXKDUGGOYFFRN-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 WOXKDUGGOYFFRN-IIBYNOLFSA-N 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims description 4
- PWUCUSITNKSTMS-CJFMBICVSA-N (6r,12ar)-6-(1,3-benzodioxol-5-yl)-2-cyclopentyl-6,7,12,12a-tetrahydro-3h-pyrazino[1,2-b]$b-carboline-1,4-quinone Chemical compound N1([C@@H](C2=C(C3=CC=CC=C3N2)C[C@@H]1C1=O)C=2C=C3OCOC3=CC=2)C(=O)CN1C1CCCC1 PWUCUSITNKSTMS-CJFMBICVSA-N 0.000 claims description 3
- 210000004204 blood vessel Anatomy 0.000 claims description 3
- OSVFAYJLSJLPQI-ZJSXRUAMSA-N chembl141307 Chemical compound C1=CC(OC)=CC=C1[C@@H]1C(NC=2C3=CC=CC=2)=C3C[C@H]2N1C(=O)CN(CC1CC1)C2=O OSVFAYJLSJLPQI-ZJSXRUAMSA-N 0.000 claims description 3
- BIVDXKUVGNOBJF-WZONZLPQSA-N chembl434797 Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C(C)C)=C1 BIVDXKUVGNOBJF-WZONZLPQSA-N 0.000 claims description 3
- XHDLVMPUSXRZOS-FOIQADDNSA-N nortadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H]3C(=O)NCC(N23)=O)=C1 XHDLVMPUSXRZOS-FOIQADDNSA-N 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- TXELQQBHZDWVMC-DYESRHJHSA-N (6r,12ar)-6-(3-chloro-4-methoxy-phenyl)-2-methyl-6,7,12,12a-tetrahydro-3h-pyrazino[1,2-b]$b-carboline-1,4-quinone Chemical compound C1=C(Cl)C(OC)=CC=C1[C@@H]1C(NC=2C3=CC=CC=2)=C3C[C@H]2N1C(=O)CN(C)C2=O TXELQQBHZDWVMC-DYESRHJHSA-N 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000001624 naphthyl group Chemical class 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 208000034189 Sclerosis Diseases 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 210000004907 gland Anatomy 0.000 claims 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 abstract description 8
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 abstract description 6
- 230000005764 inhibitory process Effects 0.000 abstract description 4
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 261
- 239000000543 intermediate Substances 0.000 description 249
- 238000002844 melting Methods 0.000 description 189
- 230000008018 melting Effects 0.000 description 189
- 239000013078 crystal Substances 0.000 description 153
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- 239000007858 starting material Substances 0.000 description 149
- 238000001953 recrystallisation Methods 0.000 description 105
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 94
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 90
- 238000004458 analytical method Methods 0.000 description 90
- 239000000243 solution Substances 0.000 description 61
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 239000007787 solid Substances 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 36
- KCUNTYMNJVXYKZ-JTQLQIEISA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical class C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 KCUNTYMNJVXYKZ-JTQLQIEISA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- 238000003556 assay Methods 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
- 239000000460 chlorine Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 229910052938 sodium sulfate Inorganic materials 0.000 description 21
- 235000011152 sodium sulphate Nutrition 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000003480 eluent Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
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- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 12
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
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- DABYEOZXRSTEGL-NSHDSACASA-N ethyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical class C1=CC=C2C(C[C@H](N)C(=O)OCC)=CNC2=C1 DABYEOZXRSTEGL-NSHDSACASA-N 0.000 description 7
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- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
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- 125000006277 halobenzyl group Chemical group 0.000 description 1
- 125000004970 halomethyl group Chemical group 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical class OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XNFNGGQRDXFYMM-UHFFFAOYSA-N hydron;methyl 2-amino-3-(1h-indol-3-yl)propanoate;chloride Chemical compound [Cl-].C1=CC=C2C(CC([NH3+])C(=O)OC)=CNC2=C1 XNFNGGQRDXFYMM-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
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- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
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- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- GVBAWCKMWZAKIB-AJSJLVFWSA-N methyl (1r,3r)-1-(1,3-benzodioxol-5-yl)-2-[(2r)-2-phenylmethoxycarbonylpyrrolidine-2-carbonyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate Chemical compound N1([C@@H](C2=C(C3=CC=CC=C3N2)C[C@@H]1C(=O)OC)C=1C=C2OCOC2=CC=1)C(=O)[C@@]1(C(=O)OCC=2C=CC=CC=2)CCCN1 GVBAWCKMWZAKIB-AJSJLVFWSA-N 0.000 description 1
- XPDHGPCPXNTVIF-WOJBJXKFSA-N methyl (1r,3r)-1-(2,3-dihydro-1h-inden-5-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2CCCC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=C1 XPDHGPCPXNTVIF-WOJBJXKFSA-N 0.000 description 1
- YCXGMYSYRWHDRT-SJLPKXTDSA-N methyl (1r,3r)-1-(3-chloro-4-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C(OC)C(Cl)=C1 YCXGMYSYRWHDRT-SJLPKXTDSA-N 0.000 description 1
- XHFOUQLMHRDZHT-QZTJIDSGSA-N methyl (1r,3r)-1-(4-methoxycarbonylphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C(C(=O)OC)C=C1 XHFOUQLMHRDZHT-QZTJIDSGSA-N 0.000 description 1
- YCCPHMBIMIJBPW-QZTJIDSGSA-N methyl (1r,3r)-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C(OC)C=C1 YCCPHMBIMIJBPW-QZTJIDSGSA-N 0.000 description 1
- NQDBWALBJVPWQF-GRKNLSHJSA-N methyl (1r,3r)-1-[3,4-bis(phenylmethoxy)phenyl]-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C=1C=CC=CC=1COC1=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C1OCC1=CC=CC=C1 NQDBWALBJVPWQF-GRKNLSHJSA-N 0.000 description 1
- LIPVUDSNGRJSQE-MAUKXSAKSA-N methyl (1r,3s)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H](N2)C(=O)OC)=C1 LIPVUDSNGRJSQE-MAUKXSAKSA-N 0.000 description 1
- XPDHGPCPXNTVIF-UXHICEINSA-N methyl (1s,3r)-1-(2,3-dihydro-1h-inden-5-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2CCCC2=CC([C@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=C1 XPDHGPCPXNTVIF-UXHICEINSA-N 0.000 description 1
- YCXGMYSYRWHDRT-AEFFLSMTSA-N methyl (1s,3r)-1-(3-chloro-4-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C(OC)C(Cl)=C1 YCXGMYSYRWHDRT-AEFFLSMTSA-N 0.000 description 1
- XHFOUQLMHRDZHT-MSOLQXFVSA-N methyl (1s,3r)-1-(4-methoxycarbonylphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C(C(=O)OC)C=C1 XHFOUQLMHRDZHT-MSOLQXFVSA-N 0.000 description 1
- YCCPHMBIMIJBPW-MSOLQXFVSA-N methyl (1s,3r)-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1([C@H]2C3=C(C4=CC=CC=C4N3)C[C@@H](N2)C(=O)OC)=CC=C(OC)C=C1 YCCPHMBIMIJBPW-MSOLQXFVSA-N 0.000 description 1
- LIPVUDSNGRJSQE-YJBOKZPZSA-N methyl (1s,3s)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2OCOC2=CC([C@H]2C3=C(C4=CC=CC=C4N3)C[C@H](N2)C(=O)OC)=C1 LIPVUDSNGRJSQE-YJBOKZPZSA-N 0.000 description 1
- MNJWYOVJMKMIFA-NSHDSACASA-N methyl (2s)-2-amino-3-(5-methyl-1h-indol-3-yl)propanoate Chemical class C1=C(C)C=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 MNJWYOVJMKMIFA-NSHDSACASA-N 0.000 description 1
- ZLZCDKZCCDYRJF-UHFFFAOYSA-N methyl 1-(1,3-benzodioxol-5-yl)-6-fluoro-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2OCOC2=CC(C2C3=C(C4=CC(F)=CC=C4N3)CC(N2)C(=O)OC)=C1 ZLZCDKZCCDYRJF-UHFFFAOYSA-N 0.000 description 1
- CKIXVBQUTDPSKD-UHFFFAOYSA-N methyl 1-(1,3-benzodioxol-5-yl)-6-methyl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2OCOC2=CC(C2C3=C(C4=CC(C)=CC=C4N3)CC(N2)C(=O)OC)=C1 CKIXVBQUTDPSKD-UHFFFAOYSA-N 0.000 description 1
- PFHXTNFFMKIEPW-UHFFFAOYSA-N methyl 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound O1CCOC2=CC(C3C4=C(C5=CC=CC=C5N4)CC(N3)C(=O)OC)=CC=C21 PFHXTNFFMKIEPW-UHFFFAOYSA-N 0.000 description 1
- CEKZLEXKVZHVSL-UHFFFAOYSA-N methyl 1-(2,3-dihydro-1-benzofuran-5-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=C2OCCC2=CC(C2C3=C(C4=CC=CC=C4N3)CC(N2)C(=O)OC)=C1 CEKZLEXKVZHVSL-UHFFFAOYSA-N 0.000 description 1
- YKRANILUQAWNOP-UHFFFAOYSA-N methyl 1-(2-chlorophenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=CC=C1Cl YKRANILUQAWNOP-UHFFFAOYSA-N 0.000 description 1
- CWEDPVSIJOZZDP-UHFFFAOYSA-N methyl 1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(Cl)C(Cl)=C1 CWEDPVSIJOZZDP-UHFFFAOYSA-N 0.000 description 1
- XXQPNGWFNGRDEE-UHFFFAOYSA-N methyl 1-(3-hydroxy-4-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(OC)C(O)=C1 XXQPNGWFNGRDEE-UHFFFAOYSA-N 0.000 description 1
- AFAUJFNORYVHAJ-UHFFFAOYSA-N methyl 1-(3-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=CC(OC)=C1 AFAUJFNORYVHAJ-UHFFFAOYSA-N 0.000 description 1
- TVICYPJVNPJQDC-UHFFFAOYSA-N methyl 1-(3-methylphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=CC(C)=C1 TVICYPJVNPJQDC-UHFFFAOYSA-N 0.000 description 1
- YTIAFXJMADYHLR-UHFFFAOYSA-N methyl 1-(4-bromothiophen-2-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC(Br)=CS1 YTIAFXJMADYHLR-UHFFFAOYSA-N 0.000 description 1
- XGVZWMNWLZHJDM-UHFFFAOYSA-N methyl 1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(Cl)C=C1 XGVZWMNWLZHJDM-UHFFFAOYSA-N 0.000 description 1
- WEFKVLCBDGWVOY-UHFFFAOYSA-N methyl 1-(4-ethoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC(OCC)=CC=C1C1C(NC=2C3=CC=CC=2)=C3CC(C(=O)OC)N1 WEFKVLCBDGWVOY-UHFFFAOYSA-N 0.000 description 1
- JBCUNMDPNMFOHP-UHFFFAOYSA-N methyl 1-(4-ethylphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC(CC)=CC=C1C1C(NC=2C3=CC=CC=2)=C3CC(C(=O)OC)N1 JBCUNMDPNMFOHP-UHFFFAOYSA-N 0.000 description 1
- BGCTZYDFAWJFDE-UHFFFAOYSA-N methyl 1-(4-hydroxy-3-methoxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(O)C(OC)=C1 BGCTZYDFAWJFDE-UHFFFAOYSA-N 0.000 description 1
- IRELGTNBKRWOMX-UHFFFAOYSA-N methyl 1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(O)C=C1 IRELGTNBKRWOMX-UHFFFAOYSA-N 0.000 description 1
- PYFUFWIRRAVVMB-UHFFFAOYSA-N methyl 1-(4-propan-2-ylphenyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(C(C)C)C=C1 PYFUFWIRRAVVMB-UHFFFAOYSA-N 0.000 description 1
- REUSWCPFIQPKBO-UHFFFAOYSA-N methyl 1-(5-bromothiophen-2-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(Br)S1 REUSWCPFIQPKBO-UHFFFAOYSA-N 0.000 description 1
- XCMDENFSIZNEEQ-UHFFFAOYSA-N methyl 1-(5-methylthiophen-2-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(C)S1 XCMDENFSIZNEEQ-UHFFFAOYSA-N 0.000 description 1
- GXDCHRVHRZKFMX-UHFFFAOYSA-N methyl 1-(furan-3-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C=1C=COC=1 GXDCHRVHRZKFMX-UHFFFAOYSA-N 0.000 description 1
- GPKLVGREGDFVRR-UHFFFAOYSA-N methyl 1-[4-(trifluoromethyl)phenyl]-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=C(C(F)(F)F)C=C1 GPKLVGREGDFVRR-UHFFFAOYSA-N 0.000 description 1
- RICWOOUOBOCYNQ-UHFFFAOYSA-N methyl 1-naphthalen-2-yl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound C1=CC=CC2=CC(C3C4=C(C5=CC=CC=C5N4)CC(N3)C(=O)OC)=CC=C21 RICWOOUOBOCYNQ-UHFFFAOYSA-N 0.000 description 1
- KYUMJWNDZQTKTB-UHFFFAOYSA-N methyl 1-thiophen-2-yl-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole-3-carboxylate Chemical compound N1C(C(=O)OC)CC(C2=CC=CC=C2N2)=C2C1C1=CC=CS1 KYUMJWNDZQTKTB-UHFFFAOYSA-N 0.000 description 1
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| GB9401090.7 | 1994-01-21 | ||
| GB9401090A GB9401090D0 (en) | 1994-01-21 | 1994-01-21 | Chemical compounds |
Publications (1)
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| KR100357411B1 true KR100357411B1 (ko) | 2003-02-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| KR1019960703922A Expired - Lifetime KR100357411B1 (ko) | 1994-01-21 | 1995-01-19 | 테트라시클릭유도체,제조방법및용도 |
Country Status (48)
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013129889A2 (ko) | 2012-02-28 | 2013-09-06 | 주식회사 서울제약 | 실데나필을 유효성분으로 함유하며 고미가 은폐된 고함량 속용필름 |
| KR20140077658A (ko) | 2012-12-14 | 2014-06-24 | 한미약품 주식회사 | 포스포다이에스터라제-5 억제제를 포함하는 츄정 |
| KR20160051468A (ko) | 2014-11-03 | 2016-05-11 | (주)퓨젠바이오농업회사법인 | 세리포리아 락세라타에 의해 생산되는 세포외다당체를 유효성분으로 함유하는 성기능개선용 조성물 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2013129889A2 (ko) | 2012-02-28 | 2013-09-06 | 주식회사 서울제약 | 실데나필을 유효성분으로 함유하며 고미가 은폐된 고함량 속용필름 |
| US10092651B2 (en) | 2012-02-28 | 2018-10-09 | Seoul Pharma Co., Ltd. | High-content fast dissolving film with masking of bitter taste comprising sildenafil as active ingredient |
| KR20140077658A (ko) | 2012-12-14 | 2014-06-24 | 한미약품 주식회사 | 포스포다이에스터라제-5 억제제를 포함하는 츄정 |
| KR20160051468A (ko) | 2014-11-03 | 2016-05-11 | (주)퓨젠바이오농업회사법인 | 세리포리아 락세라타에 의해 생산되는 세포외다당체를 유효성분으로 함유하는 성기능개선용 조성물 |
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