JP2001503055A5

JP2001503055A5 -

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Publication number: JP2001503055A5
Authority: JP; Japan
Prior art keywords: compound; alkyl; give; benzyl; acid
Prior art date: 1997-10-23
Legal status : Pending

Application number

JP1998520585A

Other languages

English (en)

Japanese (ja)

Other versions

JP2001503055A (ja

Filing date

1997-10-23

Publication date

2009-09-17

1997-10-23 Application filed filed Critical

1997-10-23 Priority claimed from PCT/US1997/019183 external-priority patent/WO1998018464A1/en

2001-03-06 Publication of JP2001503055A publication Critical patent/JP2001503055A/ja

2009-09-17 Publication of JP2001503055A5 publication Critical patent/JP2001503055A5/ja

Status Pending legal-status Critical Current

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-1 9-benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbazol-6-yl Chemical group 0.000 description 307
150000001875 compounds Chemical class 0.000 description 203
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 160
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 110
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
230000002829 reductive effect Effects 0.000 description 104
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 90
239000000243 solution Substances 0.000 description 88
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
238000002360 preparation method Methods 0.000 description 70
239000000203 mixture Substances 0.000 description 63
239000000047 product Substances 0.000 description 63
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 60
229910052938 sodium sulfate Inorganic materials 0.000 description 60
235000011152 sodium sulphate Nutrition 0.000 description 60
239000012267 brine Substances 0.000 description 59
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
238000006243 chemical reaction Methods 0.000 description 55
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
239000002253 acid Substances 0.000 description 54
238000000921 elemental analysis Methods 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 46
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
239000000741 silica gel Substances 0.000 description 43
229910002027 silica gel Inorganic materials 0.000 description 43
239000012074 organic phase Substances 0.000 description 40
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
238000000034 method Methods 0.000 description 36
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 35
229910052739 hydrogen Inorganic materials 0.000 description 33
239000001257 hydrogen Substances 0.000 description 33
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
125000005843 halogen group Chemical group 0.000 description 32
239000002585 base Substances 0.000 description 31
238000002844 melting Methods 0.000 description 29
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 28
230000008018 melting Effects 0.000 description 28
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 26
239000012312 sodium hydride Substances 0.000 description 26
229910000104 sodium hydride Inorganic materials 0.000 description 26
125000000217 alkyl group Chemical group 0.000 description 24
238000011282 treatment Methods 0.000 description 24
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
230000002452 interceptive effect Effects 0.000 description 21
125000005647 linker group Chemical group 0.000 description 21
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 21
239000002904 solvent Substances 0.000 description 21
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
229910002092 carbon dioxide Inorganic materials 0.000 description 20
229910052757 nitrogen Inorganic materials 0.000 description 20
150000003839 salts Chemical class 0.000 description 20
239000000126 substance Substances 0.000 description 20
239000012442 inert solvent Substances 0.000 description 19
239000004480 active ingredient Substances 0.000 description 18
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
UJOBWOGCFQCDNV-UHFFFAOYSA-N Carbazole Natural products C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 17
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
239000000543 intermediate Substances 0.000 description 16
125000001424 substituent group Chemical group 0.000 description 16
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 15
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 14
239000003153 chemical reaction reagent Substances 0.000 description 14
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
239000002480 mineral oil Substances 0.000 description 13
235000010446 mineral oil Nutrition 0.000 description 13
238000010992 reflux Methods 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
239000003826 tablet Substances 0.000 description 12
239000011592 zinc chloride Substances 0.000 description 12
229920002472 Starch Polymers 0.000 description 11
125000004093 cyano group Chemical group *C#N 0.000 description 11
125000000753 cycloalkyl group Chemical group 0.000 description 11
238000009472 formulation Methods 0.000 description 11
125000000623 heterocyclic group Chemical group 0.000 description 11
229910052760 oxygen Inorganic materials 0.000 description 11
239000001301 oxygen Substances 0.000 description 11
229910052763 palladium Inorganic materials 0.000 description 11
230000004044 response Effects 0.000 description 11
239000008107 starch Substances 0.000 description 11
235000019698 starch Nutrition 0.000 description 11
229910052717 sulfur Inorganic materials 0.000 description 11
239000000725 suspension Substances 0.000 description 11
230000002378 acidificating effect Effects 0.000 description 10
238000005804 alkylation reaction Methods 0.000 description 10
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 10
229910052799 carbon Inorganic materials 0.000 description 10
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 10
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 10
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
230000003287 optical effect Effects 0.000 description 10
239000000651 prodrug Substances 0.000 description 10
229940002612 prodrug Drugs 0.000 description 10
229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
235000005074 zinc chloride Nutrition 0.000 description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
230000029936 alkylation Effects 0.000 description 9
229940114079 arachidonic acid Drugs 0.000 description 9
235000021342 arachidonic acid Nutrition 0.000 description 9
125000004429 atom Chemical group 0.000 description 9
235000014113 dietary fatty acids Nutrition 0.000 description 9
229930195729 fatty acid Natural products 0.000 description 9
239000000194 fatty acid Substances 0.000 description 9
150000004665 fatty acids Chemical class 0.000 description 9
230000001404 mediated effect Effects 0.000 description 9
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 8
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
125000004414 alkyl thio group Chemical group 0.000 description 8
238000003556 assay Methods 0.000 description 8
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
125000002837 carbocyclic group Chemical group 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
238000002474 experimental method Methods 0.000 description 8
125000004076 pyridyl group Chemical group 0.000 description 8
239000011593 sulfur Substances 0.000 description 8
IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
206010003246 arthritis Diseases 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
239000003921 oil Substances 0.000 description 7
239000008194 pharmaceutical composition Substances 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
239000012453 solvate Substances 0.000 description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 6
MWXFYMWMYQVUFV-UHFFFAOYSA-N 1-methyl-9h-carbazole-4-carboxamide Chemical compound C12=CC=CC=C2NC2=C1C(C(N)=O)=CC=C2C MWXFYMWMYQVUFV-UHFFFAOYSA-N 0.000 description 6
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
230000001154 acute effect Effects 0.000 description 6
125000002877 alkyl aryl group Chemical group 0.000 description 6
125000003710 aryl alkyl group Chemical group 0.000 description 6
125000003118 aryl group Chemical group 0.000 description 6
FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 6
231100000673 dose–response relationship Toxicity 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000003814 drug Substances 0.000 description 6
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 6
239000005457 ice water Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
150000002500 ions Chemical class 0.000 description 6
LIJJGMDKVVOEFT-UHFFFAOYSA-N n-benzyl-4-methoxyaniline Chemical compound C1=CC(OC)=CC=C1NCC1=CC=CC=C1 LIJJGMDKVVOEFT-UHFFFAOYSA-N 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
239000007921 spray Substances 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 5
208000036487 Arthropathies Diseases 0.000 description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
208000012659 Joint disease Diseases 0.000 description 5
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
102000015439 Phospholipases Human genes 0.000 description 5
108010064785 Phospholipases Proteins 0.000 description 5
206010040070 Septic Shock Diseases 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
239000002775 capsule Substances 0.000 description 5
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
230000000694 effects Effects 0.000 description 5
VKCMWLOBUILIOQ-UHFFFAOYSA-N ethyl 3-bromo-2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCC(Br)C1=O VKCMWLOBUILIOQ-UHFFFAOYSA-N 0.000 description 5
MFFXVVHUKRKXCI-UHFFFAOYSA-N ethyl iodoacetate Chemical compound CCOC(=O)CI MFFXVVHUKRKXCI-UHFFFAOYSA-N 0.000 description 5
125000005842 heteroatom Chemical group 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
208000014674 injury Diseases 0.000 description 5
239000007788 liquid Substances 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 5
239000000843 powder Substances 0.000 description 5
206010039073 rheumatoid arthritis Diseases 0.000 description 5
230000036303 septic shock Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
125000004070 6 membered heterocyclic group Chemical group 0.000 description 4
HGKTVPUQDVWHQE-UHFFFAOYSA-N CC1CCC(C=2C3=CC=CC=C3NC1=2)C(=O)NN Chemical compound CC1CCC(C=2C3=CC=CC=C3NC1=2)C(=O)NN HGKTVPUQDVWHQE-UHFFFAOYSA-N 0.000 description 4
238000007126 N-alkylation reaction Methods 0.000 description 4
PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 4
206010033645 Pancreatitis Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
206010039085 Rhinitis allergic Diseases 0.000 description 4
239000013504 Triton X-100 Substances 0.000 description 4
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
201000010105 allergic rhinitis Diseases 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
239000004305 biphenyl Substances 0.000 description 4
235000010290 biphenyl Nutrition 0.000 description 4
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000001768 carboxy methyl cellulose Substances 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
230000001684 chronic effect Effects 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
125000000392 cycloalkenyl group Chemical group 0.000 description 4
238000005828 desilylation reaction Methods 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012467 final product Substances 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 4
208000030603 inherited susceptibility to asthma Diseases 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
239000000463 material Substances 0.000 description 4
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 4
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
239000000454 talc Substances 0.000 description 4
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150000003751 zinc Chemical class 0.000 description 1
229910000368 zinc sulfate Inorganic materials 0.000 description 1
239000011686 zinc sulphate Substances 0.000 description 1

JP10520585A 1996-10-30 1997-10-23 置換三環化合物群 Pending JP2001503055A (ja)