NO814264L - Fremgangsmaate ved fremstilling av terapeutisk aktive indoler - Google Patents
Fremgangsmaate ved fremstilling av terapeutisk aktive indolerInfo
- Publication number
- NO814264L NO814264L NO814264A NO814264A NO814264L NO 814264 L NO814264 L NO 814264L NO 814264 A NO814264 A NO 814264A NO 814264 A NO814264 A NO 814264A NO 814264 L NO814264 L NO 814264L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- alkyl
- pyridylmethyl
- converting
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- 238000002360 preparation method Methods 0.000 title claims description 6
- 150000002475 indoles Chemical class 0.000 title description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- -1 5-tetrazolyl Chemical group 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 239000012312 sodium hydride Substances 0.000 claims description 7
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- CLWPGTVHCNLUDO-UHFFFAOYSA-N 2-methyl-3-(pyridin-3-ylmethyl)-1h-indole Chemical compound CC=1NC2=CC=CC=C2C=1CC1=CC=CN=C1 CLWPGTVHCNLUDO-UHFFFAOYSA-N 0.000 claims description 4
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- NHQKXVADHQUNKG-UHFFFAOYSA-N 2-[2-methyl-3-(pyridin-3-ylmethyl)indol-1-yl]acetic acid Chemical compound C12=CC=CC=C2N(CC(O)=O)C(C)=C1CC1=CC=CN=C1 NHQKXVADHQUNKG-UHFFFAOYSA-N 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 claims 2
- DVLFACDLMXYFAZ-UHFFFAOYSA-N 2,5-dimethyl-3-(pyridin-3-ylmethyl)-1h-indole Chemical compound CC=1NC2=CC=C(C)C=C2C=1CC1=CC=CN=C1 DVLFACDLMXYFAZ-UHFFFAOYSA-N 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 239000000243 solution Substances 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229960001123 epoprostenol Drugs 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 230000009471 action Effects 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 108010069102 Thromboxane-A synthase Proteins 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 208000019695 Migraine disease Diseases 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 150000003180 prostaglandins Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 6
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 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 6
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 108010064377 prostacyclin synthetase Proteins 0.000 description 5
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 206010019233 Headaches Diseases 0.000 description 4
- 102000003960 Ligases Human genes 0.000 description 4
- 108090000364 Ligases Proteins 0.000 description 4
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 231100000869 headache Toxicity 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 206010027599 migraine Diseases 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- APSFTKCKWXFZHS-UHFFFAOYSA-N 3-[2-methyl-3-(pyridin-3-ylmethyl)indol-1-yl]propanenitrile Chemical compound C12=CC=CC=C2N(CCC#N)C(C)=C1CC1=CC=CN=C1 APSFTKCKWXFZHS-UHFFFAOYSA-N 0.000 description 3
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 208000007502 anemia Diseases 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 235000021342 arachidonic acid Nutrition 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- BWHXYZIESOWMKC-UHFFFAOYSA-N methyl 3-[2-cyclopropyl-3-(pyridin-3-ylmethyl)indol-1-yl]propanoate Chemical compound C=1C=CN=CC=1CC=1C2=CC=CC=C2N(CCC(=O)OC)C=1C1CC1 BWHXYZIESOWMKC-UHFFFAOYSA-N 0.000 description 3
- 210000001589 microsome Anatomy 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 3
- 229960003329 sulfinpyrazone Drugs 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PVVOZLMHGFWKCH-UHFFFAOYSA-N 2-methyl-3-(pyridin-3-ylmethyl)-1-[2-(2h-tetrazol-5-yl)ethyl]indole Chemical compound C12=CC=CC=C2N(CCC=2NN=NN=2)C(C)=C1CC1=CC=CN=C1 PVVOZLMHGFWKCH-UHFFFAOYSA-N 0.000 description 2
- KMUMTJUMVRDHJZ-UHFFFAOYSA-N 2-methyl-3-(pyridin-4-ylmethyl)-1h-indole Chemical compound CC=1NC2=CC=CC=C2C=1CC1=CC=NC=C1 KMUMTJUMVRDHJZ-UHFFFAOYSA-N 0.000 description 2
- WOTTZXSOPCHGJY-UHFFFAOYSA-N 3-[2-methyl-3-(pyridin-3-ylmethyl)indol-1-yl]propanamide Chemical compound C12=CC=CC=C2N(CCC(N)=O)C(C)=C1CC1=CC=CN=C1 WOTTZXSOPCHGJY-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- GYCMBHHDWRMZGG-UHFFFAOYSA-N Methylacrylonitrile Chemical compound CC(=C)C#N GYCMBHHDWRMZGG-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- FWDQSXPZRIMPSQ-OLYGTSNOSA-N (5z,8z,11z,14e)-15-hydroxyicosa-5,8,11,14-tetraenoic acid Chemical compound CCCCC\C(O)=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O FWDQSXPZRIMPSQ-OLYGTSNOSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
- JSFATNQSLKRBCI-VAEKSGALSA-N 15-HETE Natural products CCCCC[C@H](O)\C=C\C=C/C\C=C/C\C=C/CCCC(O)=O JSFATNQSLKRBCI-VAEKSGALSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- ANVQGHPFUNSAPE-UHFFFAOYSA-N 2-(pyridin-2-ylmethyl)-1h-indole Chemical compound C=1C2=CC=CC=C2NC=1CC1=CC=CC=N1 ANVQGHPFUNSAPE-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- TZYULGCYCYZKIQ-UHFFFAOYSA-N 2-cyclopropyl-3-(pyridin-3-ylmethyl)-1h-indole Chemical compound C=1C=CN=CC=1CC(C1=CC=CC=C1N1)=C1C1CC1 TZYULGCYCYZKIQ-UHFFFAOYSA-N 0.000 description 1
- PBDUQCQMQMXIJG-UHFFFAOYSA-N 2-methyl-3-(1-pyridin-3-ylethenyl)-1h-indole Chemical group CC=1NC2=CC=CC=C2C=1C(=C)C1=CC=CN=C1 PBDUQCQMQMXIJG-UHFFFAOYSA-N 0.000 description 1
- IQMBMOOVCKKMSP-UHFFFAOYSA-N 2-methyl-3-(1-pyridin-3-ylethyl)-1h-indole Chemical compound CC=1NC2=CC=CC=C2C=1C(C)C1=CC=CN=C1 IQMBMOOVCKKMSP-UHFFFAOYSA-N 0.000 description 1
- UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
- VOZGBVHADQJDRN-UHFFFAOYSA-N 3-[2-cyclopropyl-3-(pyridin-3-ylmethyl)indol-1-yl]propanoic acid Chemical compound C=1C=CN=CC=1CC=1C2=CC=CC=C2N(CCC(=O)O)C=1C1CC1 VOZGBVHADQJDRN-UHFFFAOYSA-N 0.000 description 1
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 1
- CQQSQBRPAJSTFB-UHFFFAOYSA-N 4-(bromomethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CBr)C=C1 CQQSQBRPAJSTFB-UHFFFAOYSA-N 0.000 description 1
- ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8040081 | 1980-12-15 |
Publications (1)
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|---|---|
| NO814264L true NO814264L (no) | 1982-06-16 |
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| NO814264A NO814264L (no) | 1980-12-15 | 1981-12-14 | Fremgangsmaate ved fremstilling av terapeutisk aktive indoler |
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| CS (1) | CS228527B2 (cs) |
| DD (1) | DD202290A5 (cs) |
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| DK (1) | DK552581A (cs) |
| ES (1) | ES8308872A1 (cs) |
| FI (1) | FI814003L (cs) |
| GR (1) | GR76355B (cs) |
| IE (1) | IE51949B1 (cs) |
| IL (1) | IL64534A0 (cs) |
| NO (1) | NO814264L (cs) |
| PH (1) | PH17576A (cs) |
| PL (1) | PL133634B1 (cs) |
| PT (1) | PT74123B (cs) |
| YU (1) | YU293481A (cs) |
| ZA (1) | ZA818665B (cs) |
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| CS229934B2 (en) * | 1981-07-07 | 1984-07-16 | Pfizer | Production method subst.indolylacryte acid derivative |
| US4460777A (en) * | 1981-11-19 | 1984-07-17 | Ciba-Geigy Corporation | N-Substituted-2-pyridylindoles |
| US4478842A (en) * | 1981-11-19 | 1984-10-23 | Ciba-Geigy Corporation | N-Substituted-2-pyridylindoles |
| US4511573A (en) * | 1983-05-17 | 1985-04-16 | Ciba-Geigy Corporation | 3-Substituted-2-(heteroaryl) indoles |
| US4536505A (en) * | 1983-05-17 | 1985-08-20 | Ciba-Geigy Corporation | Certain N-(pyridyl) indoles |
| GB8524157D0 (en) * | 1984-10-19 | 1985-11-06 | Ici America Inc | Heterocyclic amides |
| US4609733A (en) * | 1984-12-27 | 1986-09-02 | Ciba-Geigy Corporation | 3-keto-substituted-N-pyridylindoles |
| GB8609175D0 (en) * | 1986-04-15 | 1986-05-21 | Ici America Inc | Heterocyclic carboxamides |
| SK7522001A3 (en) * | 1998-03-31 | 2002-02-05 | Inst For Pharm Discovery Inc | Substituted indolealkanoic acids |
| TNSN99224A1 (fr) * | 1998-12-01 | 2005-11-10 | Inst For Pharm Discovery Inc | Methodes de reduction des niveaux de glucose et triglyceride en serum et pour suppression de l'antigenese utilisant les acides la indolealkanoique |
| AU2001232785A1 (en) * | 2000-01-14 | 2001-07-24 | The Institutes For Pharmaceutical Discovery, Llc | Methods for lowering uric acid levels |
| EP1569899B1 (en) * | 2002-12-10 | 2006-06-28 | Wyeth | Substituted 3-alkyl- and 3-arylalkyl-1h-indol-1-yl-acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1) |
| GB0324763D0 (en) * | 2003-10-23 | 2003-11-26 | Oxagen Ltd | Use of compounds in therapy |
| EP2492268A1 (en) | 2006-07-22 | 2012-08-29 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
| AU2008304657B2 (en) * | 2007-09-24 | 2013-09-05 | Allergan, Inc. | Indole compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor biological activity |
| CN101932571B (zh) | 2008-01-18 | 2014-04-23 | 奥克萨根有限公司 | 具有crth2拮抗活性的化合物 |
| US7750027B2 (en) * | 2008-01-18 | 2010-07-06 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
| US20100022613A1 (en) * | 2008-01-22 | 2010-01-28 | Oxagen Limited | Compounds Having CRTH2 Antagonist Activity |
| US8168673B2 (en) * | 2008-01-22 | 2012-05-01 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
| GB201322273D0 (en) | 2013-12-17 | 2014-01-29 | Atopix Therapeutics Ltd | Process |
| GB201407807D0 (en) * | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
| GB201407820D0 (en) * | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5173M (cs) * | 1966-02-11 | 1967-06-19 | ||
| FR7337M (cs) * | 1968-01-11 | 1969-10-13 | ||
| GB2045244B (en) | 1979-03-07 | 1983-01-26 | Pfizer Ltd | 3-1-(imidazolylalkyl) indoles |
| US4322533A (en) * | 1980-03-17 | 1982-03-30 | Lesher George Y | 1H-Indole-2,3-dione derivatives |
-
1981
- 1981-12-03 US US06/326,800 patent/US4363912A/en not_active Expired - Lifetime
- 1981-12-10 GR GR66766A patent/GR76355B/el unknown
- 1981-12-10 DE DE8181305836T patent/DE3167879D1/de not_active Expired
- 1981-12-10 EP EP81305836A patent/EP0054417B1/en not_active Expired
- 1981-12-11 PH PH26617A patent/PH17576A/en unknown
- 1981-12-14 AU AU78488/81A patent/AU525296B2/en not_active Ceased
- 1981-12-14 NO NO814264A patent/NO814264L/no unknown
- 1981-12-14 ES ES507960A patent/ES8308872A1/es not_active Expired
- 1981-12-14 CA CA000392225A patent/CA1143737A/en not_active Expired
- 1981-12-14 DK DK552581A patent/DK552581A/da not_active Application Discontinuation
- 1981-12-14 YU YU02934/81A patent/YU293481A/xx unknown
- 1981-12-14 KR KR1019810004911A patent/KR830007552A/ko unknown
- 1981-12-14 ZA ZA818665A patent/ZA818665B/xx unknown
- 1981-12-14 PT PT74123A patent/PT74123B/pt unknown
- 1981-12-14 JP JP56201438A patent/JPS57181082A/ja active Pending
- 1981-12-14 FI FI814003A patent/FI814003L/fi not_active Application Discontinuation
- 1981-12-14 DD DD81235742A patent/DD202290A5/de unknown
- 1981-12-14 IL IL64534A patent/IL64534A0/xx unknown
- 1981-12-14 IE IE2928/81A patent/IE51949B1/en unknown
- 1981-12-14 AR AR287794A patent/AR229110A1/es active
- 1981-12-15 CS CS819343A patent/CS228527B2/cs unknown
- 1981-12-15 PL PL1981234253A patent/PL133634B1/pl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57181082A (en) | 1982-11-08 |
| DK552581A (da) | 1982-06-16 |
| FI814003L (fi) | 1982-06-16 |
| PL133634B1 (en) | 1985-06-29 |
| AU525296B2 (en) | 1982-10-28 |
| GR76355B (cs) | 1984-08-06 |
| YU293481A (en) | 1984-10-31 |
| ES507960A0 (es) | 1983-10-01 |
| DE3167879D1 (en) | 1985-01-31 |
| ES8308872A1 (es) | 1983-10-01 |
| IE51949B1 (en) | 1987-04-29 |
| AR229110A1 (es) | 1983-06-15 |
| EP0054417A1 (en) | 1982-06-23 |
| IL64534A0 (en) | 1982-03-31 |
| EP0054417B1 (en) | 1984-12-19 |
| PH17576A (en) | 1984-10-01 |
| KR830007552A (ko) | 1983-10-21 |
| US4363912A (en) | 1982-12-14 |
| ZA818665B (en) | 1982-10-27 |
| DD202290A5 (de) | 1983-09-07 |
| IE812928L (en) | 1982-06-15 |
| PL234253A1 (en) | 1983-05-23 |
| CA1143737A (en) | 1983-03-29 |
| PT74123B (en) | 1983-12-19 |
| AU7848881A (en) | 1982-06-24 |
| PT74123A (en) | 1982-01-01 |
| CS228527B2 (en) | 1984-05-14 |
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