OA10920A - Carboline derivatives - Google Patents

Carboline derivatives Download PDF

Info

Publication number: OA10920A
Authority: OA; OAPI
Prior art keywords: carbolin; propene; tetrahydro; methylenedioxyphenyl; phenyl
Prior art date: 1996-05-10

Application number

OA9800218A

Other languages

English (en)

Inventor

Agnes Bombrun

Original Assignee

Icos Corp

Priority date (The priority date 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 date listed.)

1996-05-10

Filing date

1998-11-09

Publication date

2003-02-21

1996-05-10 Priority claimed from GBGB9609820.7A external-priority patent/GB9609820D0/en

1996-05-10 Priority claimed from GBGB9609777.9A external-priority patent/GB9609777D0/en

1998-11-09 Application filed by Icos Corp filed Critical Icos Corp

2003-02-21 Publication of OA10920A publication Critical patent/OA10920A/en

Links

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 claims abstract description 11
230000005764 inhibitory process Effects 0.000 claims abstract description 5
230000001225 therapeutic effect Effects 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 266
-1 methylenedioxy chain Chemical group 0.000 claims description 91
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 62
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
239000002253 acid Substances 0.000 claims description 56
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 37
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 32
150000004702 methyl esters Chemical class 0.000 claims description 25
239000005711 Benzoic acid Substances 0.000 claims description 21
229960004365 benzoic acid Drugs 0.000 claims description 21
235000010233 benzoic acid Nutrition 0.000 claims description 18
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
125000004494 ethyl ester group Chemical group 0.000 claims description 12
230000015572 biosynthetic process Effects 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
229910003827 NRaRb Inorganic materials 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
206010020751 Hypersensitivity Diseases 0.000 claims description 8
230000007815 allergy Effects 0.000 claims description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 6
201000001320 Atherosclerosis Diseases 0.000 claims description 5
206010019280 Heart failures Diseases 0.000 claims description 5
206010020772 Hypertension Diseases 0.000 claims description 5
208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
208000006011 Stroke Diseases 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
239000005864 Sulphur Substances 0.000 claims description 5
METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
206010006451 bronchitis Diseases 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
208000023819 chronic asthma Diseases 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
230000010243 gut motility Effects 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
208000002815 pulmonary hypertension Diseases 0.000 claims description 5
206010039083 rhinitis Diseases 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
208000019553 vascular disease Diseases 0.000 claims description 5
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 3
GXYCFGHNZOUYCO-UHFFFAOYSA-N CN1CCN(CC1)C1=CC=C(C=C1)C(C=C)=O Chemical compound CN1CCN(CC1)C1=CC=C(C=C1)C(C=C)=O GXYCFGHNZOUYCO-UHFFFAOYSA-N 0.000 claims description 3
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 3
125000004450 alkenylene group Chemical group 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
239000004202 carbamide Substances 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
125000005936 piperidyl group Chemical group 0.000 claims description 3
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 3
229940080818 propionamide Drugs 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
230000001684 chronic effect Effects 0.000 claims description 2
238000009109 curative therapy Methods 0.000 claims description 2
150000002367 halogens Chemical group 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
230000000414 obstructive effect Effects 0.000 claims description 2
IPBVNPXQWQGGJP-UHFFFAOYSA-N phenyl acetate Chemical compound CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 claims description 2
238000011321 prophylaxis Methods 0.000 claims description 2
230000002685 pulmonary effect Effects 0.000 claims description 2
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims 7
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 5
PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 claims 3
206010011416 Croup infectious Diseases 0.000 claims 2
201000010549 croup Diseases 0.000 claims 2
DANLZOIRUUHIIX-UHFFFAOYSA-N 4-[1-[2-chloro-6-(trifluoromethyl)benzoyl]indazol-3-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C1=CC=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C(F)(F)F DANLZOIRUUHIIX-UHFFFAOYSA-N 0.000 claims 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
206010002388 Angina unstable Diseases 0.000 claims 1
206010059245 Angiopathy Diseases 0.000 claims 1
201000001068 Prinzmetal angina Diseases 0.000 claims 1
208000007718 Stable Angina Diseases 0.000 claims 1
208000007814 Unstable Angina Diseases 0.000 claims 1
125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims 1
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
230000004064 dysfunction Effects 0.000 claims 1
201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
QVRVXSZKCXFBTE-UHFFFAOYSA-N n-[4-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)butyl]-2-(2-fluoroethoxy)-5-methylbenzamide Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1CCCCNC(=O)C1=CC(C)=CC=C1OCCF QVRVXSZKCXFBTE-UHFFFAOYSA-N 0.000 claims 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 10
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 8
230000003389 potentiating 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
229940124639 Selective inhibitor Drugs 0.000 abstract 1
230000009286 beneficial effect Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 309
238000000034 method Methods 0.000 description 253
238000004458 analytical method Methods 0.000 description 197
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 158
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
238000001953 recrystallisation Methods 0.000 description 147
239000013078 crystal Substances 0.000 description 132
239000000843 powder Substances 0.000 description 88
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 85
229910001868 water Inorganic materials 0.000 description 82
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
238000005160 1H NMR spectroscopy Methods 0.000 description 38
239000000243 solution Substances 0.000 description 34
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
239000000203 mixture Substances 0.000 description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
239000000047 product Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
239000002904 solvent Substances 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
239000003921 oil Substances 0.000 description 17
235000019198 oils Nutrition 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
238000003818 flash chromatography Methods 0.000 description 15
239000007787 solid Substances 0.000 description 15
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 14
238000010992 reflux Methods 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 12
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
229940114077 acrylic acid Drugs 0.000 description 12
238000001035 drying Methods 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 12
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 11
238000000605 extraction Methods 0.000 description 11
235000019341 magnesium sulphate Nutrition 0.000 description 11
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 11
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
235000011054 acetic acid Nutrition 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
WWXMVRYHLZMQIG-SNAWJCMRSA-N 3-nitrocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC([N+]([O-])=O)=C1 WWXMVRYHLZMQIG-SNAWJCMRSA-N 0.000 description 8
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 8
229910052681 coesite Inorganic materials 0.000 description 8
229910052906 cristobalite Inorganic materials 0.000 description 8
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000000377 silicon dioxide Substances 0.000 description 8
235000012239 silicon dioxide Nutrition 0.000 description 8
229910052682 stishovite Inorganic materials 0.000 description 8
229910052905 tridymite Inorganic materials 0.000 description 8
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
239000007832 Na2SO4 Substances 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
230000008569 process Effects 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
JOLPMPPNHIACPD-ZZXKWVIFSA-N (e)-3-(4-aminophenyl)prop-2-enoic acid Chemical compound NC1=CC=C(\C=C\C(O)=O)C=C1 JOLPMPPNHIACPD-ZZXKWVIFSA-N 0.000 description 6
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 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
239000012267 brine Substances 0.000 description 6
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
238000003756 stirring Methods 0.000 description 6
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 6
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HAEJSGLKJYIYTB-ZZXKWVIFSA-N 4-carboxycinnamic acid Chemical compound OC(=O)\C=C\C1=CC=C(C(O)=O)C=C1 HAEJSGLKJYIYTB-ZZXKWVIFSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
239000000463 material Substances 0.000 description 5
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 5
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JTVYYNVDLDECGK-UHFFFAOYSA-N 4-methoxy-n-[4-[4-[(4-methoxybenzoyl)amino]phenyl]phenyl]benzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=C(C=2C=CC(NC(=O)C=3C=CC(OC)=CC=3)=CC=2)C=C1 JTVYYNVDLDECGK-UHFFFAOYSA-N 0.000 description 4
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BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
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230000003197 catalytic effect Effects 0.000 description 4
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SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
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OA9800218A 1996-05-10 1998-11-09 Carboline derivatives OA10920A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9609820.7A GB9609820D0 (en)	1996-05-10	1996-05-10	Chemical compounds
GBGB9609777.9A GB9609777D0 (en)	1996-05-10	1996-05-10	Chemical compounds

Publications (1)

Publication Number	Publication Date
OA10920A true OA10920A (en)	2003-02-21

Family

ID=26309303

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9800218A OA10920A (en)	1996-05-10	1998-11-09	Carboline derivatives

Country Status (26)

Country	Link
US (2)	US6117881A (de)
EP (1)	EP0912567B1 (de)
JP (1)	JP3418405B2 (de)
KR (1)	KR20000010918A (de)
CN (1)	CN1067071C (de)
AP (1)	AP9801365A0 (de)
AT (1)	ATE215950T1 (de)
AU (1)	AU711885B2 (de)
BG (1)	BG102879A (de)
BR (1)	BR9709230A (de)
CA (1)	CA2253948C (de)
CZ (1)	CZ358598A3 (de)
DE (1)	DE69711882T2 (de)
EA (1)	EA199800907A1 (de)
EE (1)	EE9800390A (de)
ES (1)	ES2175404T3 (de)
HU (1)	HUP9901478A3 (de)
IL (1)	IL126951A0 (de)
IS (1)	IS4864A (de)
NO (1)	NO985222L (de)
OA (1)	OA10920A (de)
PL (1)	PL329875A1 (de)
SK (1)	SK154498A3 (de)
TR (1)	TR199802282T2 (de)
WO (1)	WO1997043287A1 (de)
YU (1)	YU49898A (de)

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1997
- 1997-05-05 BR BR9709230A patent/BR9709230A/pt not_active IP Right Cessation
- 1997-05-05 CN CN97194508A patent/CN1067071C/zh not_active Expired - Fee Related
- 1997-05-05 EA EA199800907A patent/EA199800907A1/ru unknown
- 1997-05-05 CA CA002253948A patent/CA2253948C/en not_active Expired - Fee Related
- 1997-05-05 YU YU49898A patent/YU49898A/sh unknown
- 1997-05-05 KR KR1019980709066A patent/KR20000010918A/ko not_active Withdrawn
- 1997-05-05 SK SK1544-98A patent/SK154498A3/sk unknown
- 1997-05-05 AU AU28910/97A patent/AU711885B2/en not_active Ceased
- 1997-05-05 EE EE9800390A patent/EE9800390A/xx unknown
- 1997-05-05 EP EP97922960A patent/EP0912567B1/de not_active Expired - Lifetime
- 1997-05-05 ES ES97922960T patent/ES2175404T3/es not_active Expired - Lifetime
- 1997-05-05 WO PCT/EP1997/002277 patent/WO1997043287A1/en not_active Ceased
- 1997-05-05 TR TR1998/02282T patent/TR199802282T2/xx unknown
- 1997-05-05 CZ CZ983585A patent/CZ358598A3/cs unknown
- 1997-05-05 HU HU9901478A patent/HUP9901478A3/hu unknown
- 1997-05-05 DE DE69711882T patent/DE69711882T2/de not_active Expired - Fee Related
- 1997-05-05 AT AT97922960T patent/ATE215950T1/de not_active IP Right Cessation
- 1997-05-05 JP JP54045697A patent/JP3418405B2/ja not_active Expired - Fee Related
- 1997-05-05 PL PL97329875A patent/PL329875A1/xx unknown
- 1997-05-05 IL IL12695197A patent/IL126951A0/xx unknown
- 1997-05-05 US US09/155,811 patent/US6117881A/en not_active Expired - Fee Related
- 1997-05-05 AP APAP/P/1998/001365A patent/AP9801365A0/en unknown
1998
- 1998-10-13 IS IS4864A patent/IS4864A/is unknown
- 1998-10-29 BG BG102879A patent/BG102879A/xx unknown
- 1998-11-09 OA OA9800218A patent/OA10920A/en unknown
- 1998-11-09 NO NO985222A patent/NO985222L/no not_active Application Discontinuation
2000
- 2000-06-12 US US09/592,514 patent/US6306870B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP0912567A1 (de)	1999-05-06
DE69711882D1 (en)	2002-05-16
CA2253948C (en)	2005-07-26
PL329875A1 (en)	1999-04-12
CN1067071C (zh)	2001-06-13
HUP9901478A3 (en)	1999-11-29
KR20000010918A (ko)	2000-02-25
ATE215950T1 (de)	2002-04-15
CA2253948A1 (en)	1997-11-20
IL126951A0 (en)	1999-09-22
CZ358598A3 (cs)	1999-03-17
HUP9901478A2 (hu)	1999-08-30
NO985222L (no)	1999-01-11
ES2175404T3 (es)	2002-11-16
DE69711882T2 (de)	2002-10-31
AP9801365A0 (en)	1998-12-31
IS4864A (is)	1998-10-13
BR9709230A (pt)	1999-08-10
AU711885B2 (en)	1999-10-21
BG102879A (en)	1999-09-30
US6117881A (en)	2000-09-12
AU2891097A (en)	1997-12-05
EP0912567B1 (de)	2002-04-10
JP3418405B2 (ja)	2003-06-23
JP2000513717A (ja)	2000-10-17
US6306870B1 (en)	2001-10-23
EA199800907A1 (ru)	1999-04-29
TR199802282T2 (xx)	1999-03-22
CN1218471A (zh)	1999-06-02
SK154498A3 (en)	2000-01-18
YU49898A (sh)	2000-03-21
NO985222D0 (no)	1998-11-09
EE9800390A (et)	1999-06-15
WO1997043287A1 (en)	1997-11-20

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US6043252A (en)	2000-03-28	Carboline derivatives
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