FI114025B - Uudet heterosykliset yhdisteet - Google Patents
Uudet heterosykliset yhdisteet Download PDFInfo
- Publication number
- FI114025B FI114025B FI962749A FI962749A FI114025B FI 114025 B FI114025 B FI 114025B FI 962749 A FI962749 A FI 962749A FI 962749 A FI962749 A FI 962749A FI 114025 B FI114025 B FI 114025B
- Authority
- FI
- Finland
- Prior art keywords
- propyl
- dibenzo
- dihydro
- added
- piperidinecarboxylic acid
- Prior art date
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 208000007920 Neurogenic Inflammation Diseases 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 70
- 239000011541 reaction mixture Substances 0.000 claims description 45
- -1 carbomethoxy-1-piperidyl Chemical group 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- FEQDVTZJXGQYJE-UHFFFAOYSA-N methyl 1-(3-phenothiazin-10-ylpropyl)piperidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 FEQDVTZJXGQYJE-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- NJLAEBZVVOVDPS-UHFFFAOYSA-N hexyl 1-(3-phenothiazin-10-ylpropyl)piperidine-3-carboxylate Chemical compound C1C(C(=O)OCCCCCC)CCCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 NJLAEBZVVOVDPS-UHFFFAOYSA-N 0.000 claims description 3
- 229950000688 phenothiazine Drugs 0.000 claims description 3
- DTGHJYIMUYGTNH-UHFFFAOYSA-N 1-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]-3,6-dihydro-2h-pyridine-5-carboxylic acid Chemical compound C1C(C(=O)O)=CCCN1CCCN1C2=CC=CC=C2CCC2=CC=CC=C21 DTGHJYIMUYGTNH-UHFFFAOYSA-N 0.000 claims description 2
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- SJJUKGVRGZOKFH-MRXNPFEDSA-N (3r)-1-(3-fluoren-9-ylidenepropyl)piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCC=C1C2=CC=CC=C2C2=CC=CC=C21 SJJUKGVRGZOKFH-MRXNPFEDSA-N 0.000 claims 1
- VTBYWEFVZUSBMD-MRXNPFEDSA-N (3r)-1-(3-phenothiazin-10-ylpropyl)piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 VTBYWEFVZUSBMD-MRXNPFEDSA-N 0.000 claims 1
- AOUKABACXBPGLP-MRXNPFEDSA-N (3r)-1-(3-phenoxazin-10-ylpropyl)piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCN1C2=CC=CC=C2OC2=CC=CC=C21 AOUKABACXBPGLP-MRXNPFEDSA-N 0.000 claims 1
- XJLZRTAXJOFCRE-LJQANCHMSA-N (3r)-1-[2-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)ethyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCN1C2=CC=CC=C2CCC2=CC=CC=C21 XJLZRTAXJOFCRE-LJQANCHMSA-N 0.000 claims 1
- IIMZFYZCCHOKSN-LJQANCHMSA-N (3r)-1-[3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCN1C2=CC(Cl)=CC=C2CCC2=CC=CC=C21 IIMZFYZCCHOKSN-LJQANCHMSA-N 0.000 claims 1
- YZPGLTDLJQQMER-OAQYLSRUSA-N (3r)-1-[3-(2-methyl-5,6-dihydrodibenzo[1,2-e:1',2'-f][7]annulen-11-ylidene)propyl]piperidine-3-carboxylic acid Chemical compound C12=CC(C)=CC=C2CCC2=CC=CC=C2C1=CCCN1CCC[C@@H](C(O)=O)C1 YZPGLTDLJQQMER-OAQYLSRUSA-N 0.000 claims 1
- ZCFXYESDNJLOPW-HXUWFJFHSA-N (3r)-1-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCN1C2=CC=CC=C2CCC2=CC=CC=C21 ZCFXYESDNJLOPW-HXUWFJFHSA-N 0.000 claims 1
- OKKZSYFRRYMKIC-QGZVFWFLSA-N (3r)-1-[3-(5-methyl-6-oxobenzo[b][1,4]benzodiazepin-11-yl)propyl]piperidine-3-carboxylic acid Chemical compound C12=CC=CC=C2C(=O)N(C)C2=CC=CC=C2N1CCCN1CCC[C@@H](C(O)=O)C1 OKKZSYFRRYMKIC-QGZVFWFLSA-N 0.000 claims 1
- YKCVVBHYKCJTIC-MRXNPFEDSA-N (3r)-1-[3-(5-oxophenothiazin-10-yl)propyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCN1C2=CC=CC=C2S(=O)C2=CC=CC=C21 YKCVVBHYKCJTIC-MRXNPFEDSA-N 0.000 claims 1
- DRTNQSXMCDVPDW-HXUWFJFHSA-N (3r)-1-[3-(6,11-dihydro-5h-dibenzo[1,2-a:1',2'-e][7]annulen-11-yl)propyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCC1C2=CC=CC=C2CCC2=CC=CC=C21 DRTNQSXMCDVPDW-HXUWFJFHSA-N 0.000 claims 1
- TXAIAJFIOBJOMA-OAHLLOKOSA-N (3r)-1-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 TXAIAJFIOBJOMA-OAHLLOKOSA-N 0.000 claims 1
- JLRWUCSMFVXWKQ-OAQYLSRUSA-N (3r)-1-[4-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)butyl]piperidine-3-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCCN1CCCCN1C2=CC=CC=C2CCC2=CC=CC=C21 JLRWUCSMFVXWKQ-OAQYLSRUSA-N 0.000 claims 1
- ZCFXYESDNJLOPW-FQEVSTJZSA-N (3s)-1-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]piperidine-3-carboxylic acid Chemical compound C1[C@@H](C(=O)O)CCCN1CCCN1C2=CC=CC=C2CCC2=CC=CC=C21 ZCFXYESDNJLOPW-FQEVSTJZSA-N 0.000 claims 1
- RXWDEUWOJGGNHU-FQEVSTJZSA-N (3s)-1-[3-(5,6-dihydrodibenzo[1,2-a:1',2'-e][7]annulen-11-ylidene)propyl]piperidine-3-carboxylic acid Chemical compound C1[C@@H](C(=O)O)CCCN1CCC=C1C2=CC=CC=C2CCC2=CC=CC=C21 RXWDEUWOJGGNHU-FQEVSTJZSA-N 0.000 claims 1
- FWKATONZUDMDBG-UHFFFAOYSA-N 1-(3-thioxanthen-9-ylidenepropyl)piperidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCCN1CCC=C1C2=CC=CC=C2SC2=CC=CC=C21 FWKATONZUDMDBG-UHFFFAOYSA-N 0.000 claims 1
- HIAVZZYGFRWZNI-UHFFFAOYSA-N 1-[3-(5,6-dihydrodibenzo[1,2-a:1',2'-e][7]annulen-11-ylidene)propyl]-3,6-dihydro-2h-pyridine-5-carboxylic acid Chemical compound C1C(C(=O)O)=CCCN1CCC=C1C2=CC=CC=C2CCC2=CC=CC=C21 HIAVZZYGFRWZNI-UHFFFAOYSA-N 0.000 claims 1
- OWOXYUUFFMTIPR-UHFFFAOYSA-N 2-[1-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]pyrrolidin-3-yl]acetic acid Chemical compound C1C(CC(=O)O)CCN1CCCN1C2=CC=CC=C2CCC2=CC=CC=C21 OWOXYUUFFMTIPR-UHFFFAOYSA-N 0.000 claims 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims 1
- CGCUTOHNZNAUIX-UHFFFAOYSA-N CCCCCCOC(=O)C1CCCCN1CCCC2=CC3=C(C=C2)NC4=CC=CC=C4S3 Chemical compound CCCCCCOC(=O)C1CCCCN1CCCC2=CC3=C(C=C2)NC4=CC=CC=C4S3 CGCUTOHNZNAUIX-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 110
- 150000002148 esters Chemical class 0.000 abstract description 20
- 150000001735 carboxylic acids Chemical class 0.000 abstract description 5
- 230000004054 inflammatory process Effects 0.000 abstract description 5
- 230000004968 inflammatory condition Effects 0.000 abstract description 4
- 208000004296 neuralgia Diseases 0.000 abstract description 3
- 230000001991 pathophysiological effect Effects 0.000 abstract description 3
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 abstract description 3
- 230000000917 hyperalgesic effect Effects 0.000 abstract description 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 107
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
- 239000002904 solvent Substances 0.000 description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 239000000243 solution Substances 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000010992 reflux Methods 0.000 description 44
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 239000012074 organic phase Substances 0.000 description 39
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 38
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 38
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 34
- 239000003921 oil Substances 0.000 description 34
- 235000019198 oils Nutrition 0.000 description 34
- 239000012071 phase Substances 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- 229910004298 SiO 2 Inorganic materials 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 239000000047 product Substances 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
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- 238000004440 column chromatography Methods 0.000 description 16
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- 238000001704 evaporation Methods 0.000 description 15
- 230000008020 evaporation Effects 0.000 description 15
- 239000000284 extract Substances 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
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- 239000012359 Methanesulfonyl chloride Substances 0.000 description 10
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 208000002193 Pain Diseases 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 230000036407 pain Effects 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- HHPGQKZOPPDLNH-OGFXRTJISA-N 2,3-dihydroxybutanedioic acid;ethyl (3r)-piperidine-3-carboxylate Chemical compound OC(=O)C(O)C(O)C(O)=O.CCOC(=O)[C@@H]1CCCNC1 HHPGQKZOPPDLNH-OGFXRTJISA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- HJNHUFQGDJLQRS-UHFFFAOYSA-N 2-(3-bromopropoxy)oxane Chemical compound BrCCCOC1CCCCO1 HJNHUFQGDJLQRS-UHFFFAOYSA-N 0.000 description 5
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- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 4
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
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- 229960003692 gamma aminobutyric acid Drugs 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
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- 230000005764 inhibitory process Effects 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- DLCIJMPSJTVVHJ-UHFFFAOYSA-N 10-(3-chloropropyl)phenothiazine Chemical compound C1=CC=C2N(CCCCl)C3=CC=CC=C3SC2=C1 DLCIJMPSJTVVHJ-UHFFFAOYSA-N 0.000 description 3
- OIUPFQXPTICAHQ-UHFFFAOYSA-N 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propan-1-ol Chemical compound C1CC2=CC=CC=C2N(CCCO)C2=CC=CC=C21 OIUPFQXPTICAHQ-UHFFFAOYSA-N 0.000 description 3
- NLKSFKLPWZLDGG-UHFFFAOYSA-N 5-methyl-11h-benzo[b][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)C2=CC=CC=C2NC2=CC=CC=C21 NLKSFKLPWZLDGG-UHFFFAOYSA-N 0.000 description 3
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- 229910010082 LiAlH Inorganic materials 0.000 description 3
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- 238000005481 NMR spectroscopy Methods 0.000 description 3
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- 230000009471 action Effects 0.000 description 3
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- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
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- VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 3
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- MIRJGPRWVWWNQH-UHFFFAOYSA-N ethyl 1,2,3,6-tetrahydropyridine-5-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CCCNC1 MIRJGPRWVWWNQH-UHFFFAOYSA-N 0.000 description 1
- SPAHCNCHXSVNMA-UHFFFAOYSA-N ethyl 1-(3-thioxanthen-9-ylidenepropyl)piperidine-3-carboxylate Chemical compound C1C(C(=O)OCC)CCCN1CCC=C1C2=CC=CC=C2SC2=CC=CC=C21 SPAHCNCHXSVNMA-UHFFFAOYSA-N 0.000 description 1
- JUHIFJIQOOLUQX-UHFFFAOYSA-N ethyl 1-[3-(5,6-dihydrodibenzo[1,2-a:1',2'-e][7]annulen-11-ylidene)propyl]-4-phenylpiperidine-4-carboxylate Chemical compound C1CN(CCC=C2C3=CC=CC=C3CCC3=CC=CC=C32)CCC1(C(=O)OCC)C1=CC=CC=C1 JUHIFJIQOOLUQX-UHFFFAOYSA-N 0.000 description 1
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
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- 239000006193 liquid solution Substances 0.000 description 1
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- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
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- QKONQSPVWNDJJQ-UHFFFAOYSA-N methyl 2-pyrrolidin-3-ylacetate Chemical compound COC(=O)CC1CCNC1 QKONQSPVWNDJJQ-UHFFFAOYSA-N 0.000 description 1
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- 150000002990 phenothiazines Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
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- DKORSYDQYFVQNS-UHFFFAOYSA-N propyl methanesulfonate Chemical compound CCCOS(C)(=O)=O DKORSYDQYFVQNS-UHFFFAOYSA-N 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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Classifications
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Anesthesiology (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK1994 | 1994-01-04 | ||
| DK1994 | 1994-01-04 | ||
| DK129094 | 1994-11-09 | ||
| DK129094 | 1994-11-09 | ||
| PCT/DK1995/000002 WO1995018793A1 (en) | 1994-01-04 | 1995-01-03 | Novel heterocyclic compounds |
| DK9500002 | 1995-01-03 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI962749A0 FI962749A0 (fi) | 1996-07-04 |
| FI962749L FI962749L (fi) | 1996-09-04 |
| FI114025B true FI114025B (fi) | 2004-07-30 |
Family
ID=26063135
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI962749A FI114025B (fi) | 1994-01-04 | 1996-07-04 | Uudet heterosykliset yhdisteet |
Country Status (31)
| Country | Link |
|---|---|
| US (8) | US5595989A (enExample) |
| EP (1) | EP0738262B1 (enExample) |
| JP (1) | JP2944221B2 (enExample) |
| KR (1) | KR100329450B1 (enExample) |
| CN (1) | CN1083431C (enExample) |
| AT (1) | ATE191909T1 (enExample) |
| AU (1) | AU691858B2 (enExample) |
| BG (1) | BG100692A (enExample) |
| BR (1) | BR9506452A (enExample) |
| CA (1) | CA2180238A1 (enExample) |
| CZ (1) | CZ286109B6 (enExample) |
| DE (1) | DE69516394T2 (enExample) |
| DK (1) | DK0738262T3 (enExample) |
| ES (1) | ES2147837T3 (enExample) |
| FI (1) | FI114025B (enExample) |
| GR (1) | GR3033967T3 (enExample) |
| HU (1) | HUT75878A (enExample) |
| IL (1) | IL112222A (enExample) |
| MY (1) | MY113463A (enExample) |
| NO (1) | NO306295B1 (enExample) |
| NZ (1) | NZ277763A (enExample) |
| PE (1) | PE45095A1 (enExample) |
| PL (1) | PL180209B1 (enExample) |
| PT (1) | PT738262E (enExample) |
| RU (1) | RU2167152C2 (enExample) |
| SG (1) | SG50602A1 (enExample) |
| SI (1) | SI9520023A (enExample) |
| SK (1) | SK88196A3 (enExample) |
| TW (1) | TW300887B (enExample) |
| UA (1) | UA47396C2 (enExample) |
| WO (1) | WO1995018793A1 (enExample) |
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| US6239148B1 (en) | 1994-01-04 | 2001-05-29 | Novo Nordisk A/S | N-substituted azaheterocyclic carboxylic acids and esters thereof |
| MY113463A (en) * | 1994-01-04 | 2002-03-30 | Novo Nordisk As | Novel heterocyclic compounds |
| US6110913A (en) * | 1994-01-04 | 2000-08-29 | Novo Nordisk A/S | N-substituted azaheterocyclic carboxylic acids and esters thereof |
| US5716949A (en) * | 1995-04-07 | 1998-02-10 | Novo Nordisk A/S | Heterocyclic compounds |
| US5952352A (en) * | 1995-04-07 | 1999-09-14 | Novo Nordisk A/S | Heterocyclic compounds |
| US5962449A (en) | 1995-04-07 | 1999-10-05 | Novo Nordisk A/S | Tricyclic compounds in treating hyperalgesic conditions and NIDDM |
| UA54385C2 (uk) * | 1995-04-07 | 2003-03-17 | Ново Нордіск А/С | N-заміщені азагетероциклічні карбонові кислоти та їх ефіри, спосіб їх одержання, фармацевтична композиція та спосіб лікування |
| US5698551A (en) * | 1995-04-07 | 1997-12-16 | Novo Nordisk A/S | Heterocyclic compounds |
| KR20000064411A (ko) | 1995-12-15 | 2000-11-06 | 한센 핀 베네드, 안네 제헤르, 웨이콥 마리안느 | 새로운방법 |
| US6323206B1 (en) | 1996-07-12 | 2001-11-27 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| HUP0000088A3 (en) * | 1996-10-04 | 2000-09-28 | Novo Nordisk As | N-substituted azaheterocyclic compounds, process for producing them and pharmaceutical compositions containing them |
| ZA978792B (en) * | 1996-10-04 | 1998-04-06 | Novo Nordisk As | N-substituted azaheterocyclic compounds. |
| KR20000048899A (ko) * | 1996-10-04 | 2000-07-25 | 한센 핀 베네드, 안네 제헤르, 웨이콥 마리안느 | 1,4-디치환 피페라진 |
| US6040318A (en) * | 1997-06-25 | 2000-03-21 | Novo Nordisk A/S | Tricycle substituted with azaheterocyclic carboxylic acids |
| EP1049684A1 (en) | 1997-10-27 | 2000-11-08 | Dr. Reddy's Research Foundation | Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them |
| CA2319077A1 (en) | 1998-01-21 | 1999-07-29 | Yoshisuke Nakasato | Chemokine receptor antagonists and methods of use therefor |
| US6613905B1 (en) | 1998-01-21 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6509346B2 (en) | 1998-01-21 | 2003-01-21 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| JP2002501052A (ja) * | 1998-01-21 | 2002-01-15 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | ケモカイン受容体アンタゴニストおよびその使用方法 |
| ES2137136B1 (es) * | 1998-05-18 | 2000-07-01 | Esteve Labor Dr | Empleo de derivados de aril (o heteroaril) azolilcarbinoles en la elaboracion de un medicamento para el tratamiento de la inflamacion neurogenica. |
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