NO314544B1 - Nye imidazolinforbindelser, fremgangsmåte ved deres fremstilling og farmasöytiske sammensetninger inneholdende dem - Google Patents
Nye imidazolinforbindelser, fremgangsmåte ved deres fremstilling og farmasöytiske sammensetninger inneholdende dem Download PDFInfo
- Publication number
- NO314544B1 NO314544B1 NO19996284A NO996284A NO314544B1 NO 314544 B1 NO314544 B1 NO 314544B1 NO 19996284 A NO19996284 A NO 19996284A NO 996284 A NO996284 A NO 996284A NO 314544 B1 NO314544 B1 NO 314544B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- dihydro
- symbol
- compounds
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 150000002462 imidazolines Chemical class 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 57
- 150000001875 compounds Chemical class 0.000 claims abstract description 215
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 239000002253 acid Substances 0.000 claims abstract description 23
- -1 cyano, nitro, amino Chemical group 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 30
- 125000003003 spiro group Chemical group 0.000 claims description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 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 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 239000000377 silicon dioxide Substances 0.000 claims description 12
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 10
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 claims description 10
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 10
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- VOZDIWQCBQGDFQ-UHFFFAOYSA-N 5-(1,2,3,4-tetrahydronaphthalen-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound C1CC2=CC=CC=C2CC1CC1CNC=N1 VOZDIWQCBQGDFQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 claims description 5
- 229910010084 LiAlH4 Inorganic materials 0.000 claims description 5
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- VUEUPAZWNIDHOX-UHFFFAOYSA-N 5-[(4,4-dimethyl-3h-naphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC=CC=C2C(C)(C)CC=1CC1CNC=N1 VUEUPAZWNIDHOX-UHFFFAOYSA-N 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- XYKLDBVIJCCWKG-UHFFFAOYSA-N 5-(1-benzofuran-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC=CC=C2OC=1CC1CNC=N1 XYKLDBVIJCCWKG-UHFFFAOYSA-N 0.000 claims description 2
- AFODDVAUCQPPQC-UHFFFAOYSA-N 5-[(5,6-difluoro-2,3-dihydro-1h-inden-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C1C=2C=C(F)C(F)=CC=2CC1CC1CNC=N1 AFODDVAUCQPPQC-UHFFFAOYSA-N 0.000 claims description 2
- WWUPWXOAAVDTKR-UHFFFAOYSA-N 5-[(7-fluoro-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC(F)=CC=C2CCC=1CC1CNC=N1 WWUPWXOAAVDTKR-UHFFFAOYSA-N 0.000 claims description 2
- LICJPBUGTHDADI-UHFFFAOYSA-N 5-[(8-chloronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C1=C2C(Cl)=CC=CC2=CC=C1CC1CNC=N1 LICJPBUGTHDADI-UHFFFAOYSA-N 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 206010013654 Drug abuse Diseases 0.000 claims description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
- 206010033664 Panic attack Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 238000007059 Strecker synthesis reaction Methods 0.000 claims description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910000091 aluminium hydride Inorganic materials 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 208000001022 morbid obesity Diseases 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 208000019906 panic disease Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000019899 phobic disease Diseases 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 208000011117 substance-related disease Diseases 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims 5
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims 3
- WNPGIHKSPQIODH-UHFFFAOYSA-N 5-(3,4-dihydronaphthalen-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC=CC=C2CCC=1CC1CNC=N1 WNPGIHKSPQIODH-UHFFFAOYSA-N 0.000 claims 1
- HBMJQYDGBNSZMC-UHFFFAOYSA-N 5-[(5-fluoro-2,3-dihydro-1h-inden-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C1C2=CC(F)=CC=C2CC1CC1CNC=N1 HBMJQYDGBNSZMC-UHFFFAOYSA-N 0.000 claims 1
- MBYRWLFNVFMLCK-UHFFFAOYSA-N 5-[(8-chloro-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C=1C=2C(Cl)=CC=CC=2CCC=1CC1CNC=N1 MBYRWLFNVFMLCK-UHFFFAOYSA-N 0.000 claims 1
- OMVHNYLXKNAIID-UHFFFAOYSA-N 5-[(8-methoxy-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C=1C=2C(OC)=CC=CC=2CCC=1CC1CNC=N1 OMVHNYLXKNAIID-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 abstract description 2
- 125000003282 alkyl amino group Chemical group 0.000 abstract 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 2
- 229940083254 peripheral vasodilators imidazoline derivative Drugs 0.000 abstract 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 125000004963 sulfonylalkyl group Chemical group 0.000 abstract 1
- 125000004001 thioalkyl group Chemical group 0.000 abstract 1
- 238000004452 microanalysis Methods 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
- 239000000243 solution Substances 0.000 description 68
- 239000000203 mixture Substances 0.000 description 66
- 238000002844 melting Methods 0.000 description 51
- 230000008018 melting Effects 0.000 description 51
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
- 239000003921 oil Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- 239000000725 suspension Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 229910001868 water Inorganic materials 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- 238000007792 addition Methods 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000011534 incubation Methods 0.000 description 9
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000009835 boiling Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- RNUHTTMKFYIFCV-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-(1,2,3,4-tetrahydronaphthalen-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C1CC2=CC=CC=C2CC1CC1CN=CN1 RNUHTTMKFYIFCV-WLHGVMLRSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 239000001530 fumaric acid Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- KCCWGKLXVFMDKQ-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-(3,4-dihydronaphthalen-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC=CC=C2CCC=1CC1CN=CN1 KCCWGKLXVFMDKQ-WLHGVMLRSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
- RFKBZLNEAAPIES-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(7-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C1C2=CC(F)=CC=C2CCC1CC1CN=CN1 RFKBZLNEAAPIES-WLHGVMLRSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 239000000674 adrenergic antagonist Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 238000005567 liquid scintillation counting Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000000407 monoamine reuptake Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 230000000966 norepinephrine reuptake Effects 0.000 description 3
- 230000000697 serotonin reuptake Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- AOCQQMOCNSDVPM-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-(3,4-dihydronaphthalen-2-ylmethyl)-5-methyl-1,4-dihydroimidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC=CC=C2CCC=1CC1(C)CN=CN1 AOCQQMOCNSDVPM-WLHGVMLRSA-N 0.000 description 2
- AJRPEVBKTBSFDV-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(2-methyl-3,4-dihydro-1h-naphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C1CC2=CC=CC=C2CC1(C)CC1CN=CN1 AJRPEVBKTBSFDV-WLHGVMLRSA-N 0.000 description 2
- NNTBVZRMSIUVRV-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(6-methyl-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C1CC2=CC(C)=CC=C2C=C1CC1CN=CN1 NNTBVZRMSIUVRV-WLHGVMLRSA-N 0.000 description 2
- JFUCNZHCGCLSBN-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(7-fluoro-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC(F)=CC=C2CCC=1CC1CN=CN1 JFUCNZHCGCLSBN-WLHGVMLRSA-N 0.000 description 2
- RJKDBHQYHBDRTK-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(7-methoxy-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC(OC)=CC=C2CCC=1CC1CN=CN1 RJKDBHQYHBDRTK-WLHGVMLRSA-N 0.000 description 2
- OPNUFVVOTQYALA-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(7-methyl-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC(C)=CC=C2CCC=1CC1CN=CN1 OPNUFVVOTQYALA-WLHGVMLRSA-N 0.000 description 2
- DNGRWWLJMFKCBW-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(8-chloro-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C=2C(Cl)=CC=CC=2CCC=1CC1CN=CN1 DNGRWWLJMFKCBW-WLHGVMLRSA-N 0.000 description 2
- QAAKGSIWKKQWCN-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(8-fluoro-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C=2C(F)=CC=CC=2CCC=1CC1CN=CN1 QAAKGSIWKKQWCN-WLHGVMLRSA-N 0.000 description 2
- QQQLEWJJPIZBNJ-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(8-methoxy-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C=2C(OC)=CC=CC=2CCC=1CC1CN=CN1 QQQLEWJJPIZBNJ-WLHGVMLRSA-N 0.000 description 2
- GCOSGRKOYRFWOS-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(8-methyl-3,4-dihydronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C=2C(C)=CC=CC=2CCC=1CC1CN=CN1 GCOSGRKOYRFWOS-WLHGVMLRSA-N 0.000 description 2
- WIWKZBGTWGJWBK-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-methyl-5-(1,2,3,4-tetrahydronaphthalen-2-ylmethyl)-1,4-dihydroimidazole Chemical compound OC(=O)\C=C\C(O)=O.C1CC2=CC=CC=C2CC1CC1(C)CN=CN1 WIWKZBGTWGJWBK-WLHGVMLRSA-N 0.000 description 2
- ISVMFIBANYEUFI-UHFFFAOYSA-N 1-(3,4-dihydronaphthalen-2-yl)propan-2-one Chemical compound C1=CC=C2CCC(CC(=O)C)=CC2=C1 ISVMFIBANYEUFI-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- ANFXTILBDGTSEG-UHFFFAOYSA-N 1-methyl-4,5-dihydroimidazole Chemical compound CN1CCN=C1 ANFXTILBDGTSEG-UHFFFAOYSA-N 0.000 description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
- GIDJTOBYSRLXHM-UHFFFAOYSA-N 2-(2-methyl-3,4-dihydro-1h-naphthalen-2-yl)acetaldehyde Chemical compound C1=CC=C2CC(C)(CC=O)CCC2=C1 GIDJTOBYSRLXHM-UHFFFAOYSA-N 0.000 description 2
- WETRBJOSGIDJHQ-UHFFFAOYSA-N 2-(3,4-dihydronaphthalen-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC=CC=C2CCC=1CC1=NCCN1 WETRBJOSGIDJHQ-UHFFFAOYSA-N 0.000 description 2
- CJEVKAYEFHZATQ-WLHGVMLRSA-N 5-(1-benzofuran-2-ylmethyl)-4,5-dihydro-1h-imidazole;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC=CC=C2OC=1CC1CNC=N1 CJEVKAYEFHZATQ-WLHGVMLRSA-N 0.000 description 2
- VUPGQWJGLPAGMZ-UHFFFAOYSA-N 8-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1CCC(=O)C2=C1C=CC=C2Cl VUPGQWJGLPAGMZ-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- YEODOPOFBSVIHK-UHFFFAOYSA-N ethyl 2-(8-chloro-3,4-dihydronaphthalen-2-yl)acetate Chemical compound C1=CC=C2CCC(CC(=O)OCC)=CC2=C1Cl YEODOPOFBSVIHK-UHFFFAOYSA-N 0.000 description 2
- LNPCXNGEMVIGGL-UHFFFAOYSA-N ethyl 2-diethoxyphosphoryloxyprop-2-enoate Chemical compound CCOC(=O)C(=C)OP(=O)(OCC)OCC LNPCXNGEMVIGGL-UHFFFAOYSA-N 0.000 description 2
- 210000005153 frontal cortex Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229950000323 napamezole Drugs 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 229950004211 nisoxetine Drugs 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 2
- 229960002296 paroxetine Drugs 0.000 description 2
- 230000006461 physiological response Effects 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 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 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
- YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 1
- UTYSJEXYWDKRGS-UHFFFAOYSA-N (4-fluoro-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound C1=CC(F)=C2CC(CO)CC2=C1 UTYSJEXYWDKRGS-UHFFFAOYSA-N 0.000 description 1
- MYIUBTXFTRVRLQ-UHFFFAOYSA-N (5,6-difluoro-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound FC1=C(F)C=C2CC(CO)CC2=C1 MYIUBTXFTRVRLQ-UHFFFAOYSA-N 0.000 description 1
- RJVUKUITYAETFV-UHFFFAOYSA-N (5,6-dimethyl-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound C1=C(C)C(C)=CC2=C1CC(CO)C2 RJVUKUITYAETFV-UHFFFAOYSA-N 0.000 description 1
- VFXRFXAEZVQAHB-UHFFFAOYSA-N (5-fluoro-1-benzofuran-2-yl)methanol Chemical compound FC1=CC=C2OC(CO)=CC2=C1 VFXRFXAEZVQAHB-UHFFFAOYSA-N 0.000 description 1
- KFSZEXKUEMSKDW-UHFFFAOYSA-N (5-fluoro-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound C1=C(F)C=C2CC(CO)CC2=C1 KFSZEXKUEMSKDW-UHFFFAOYSA-N 0.000 description 1
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 1
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
- HGHGLDHWCOFIRY-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-(1h-inden-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC=CC=C2CC=1CC1CN=CN1 HGHGLDHWCOFIRY-WLHGVMLRSA-N 0.000 description 1
- JEVRSRCNYAOGJT-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-(naphthalen-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C=C2C=CC=CC2=CC=1CC1CN=CN1 JEVRSRCNYAOGJT-WLHGVMLRSA-N 0.000 description 1
- CGAHZBGVCJLMHK-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(5,6-dimethyl-2,3-dihydro-1h-inden-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C1C=2C=C(C)C(C)=CC=2CC1CC1CN=CN1 CGAHZBGVCJLMHK-WLHGVMLRSA-N 0.000 description 1
- NOHIVOQFUJKBMS-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(7-fluoronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C=1C2=CC(F)=CC=C2C=CC=1CC1CN=CN1 NOHIVOQFUJKBMS-WLHGVMLRSA-N 0.000 description 1
- NJOJAVJUOZVKGY-WLHGVMLRSA-N (e)-but-2-enedioic acid;5-[(8-chloronaphthalen-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound OC(=O)\C=C\C(O)=O.C1=C2C(Cl)=CC=CC2=CC=C1CC1CN=CN1 NJOJAVJUOZVKGY-WLHGVMLRSA-N 0.000 description 1
- HSOMHPHYGAQRTF-UHFFFAOYSA-N 1-benzofuran-2-ylmethanol Chemical compound C1=CC=C2OC(CO)=CC2=C1 HSOMHPHYGAQRTF-UHFFFAOYSA-N 0.000 description 1
- DSPXASHHKFVPCL-UHFFFAOYSA-N 1-isocyanocyclohexene Chemical compound [C-]#[N+]C1=CCCCC1 DSPXASHHKFVPCL-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- LOHORGOLEKOPOU-UHFFFAOYSA-N 2-(1,2,3,4-tetrahydronaphthalen-2-yl)acetaldehyde Chemical compound C1=CC=C2CC(CC=O)CCC2=C1 LOHORGOLEKOPOU-UHFFFAOYSA-N 0.000 description 1
- CSFKZAORDHRIPG-UHFFFAOYSA-N 2-(1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalen-1-yl)acetaldehyde Chemical compound C1=CC=C2C3C(CC=O)C3CCC2=C1 CSFKZAORDHRIPG-UHFFFAOYSA-N 0.000 description 1
- BJOYKRKDPGCHKQ-UHFFFAOYSA-N 2-(3,4-dihydronaphthalen-2-yl)acetaldehyde Chemical compound C1=CC=C2CCC(CC=O)=CC2=C1 BJOYKRKDPGCHKQ-UHFFFAOYSA-N 0.000 description 1
- GTYXMXQRELWSKW-UHFFFAOYSA-N 2-(4,4-dimethyl-3h-naphthalen-2-yl)acetaldehyde Chemical compound C1=CC=C2C(C)(C)CC(CC=O)=CC2=C1 GTYXMXQRELWSKW-UHFFFAOYSA-N 0.000 description 1
- VRLJFRODHVSTIK-UHFFFAOYSA-N 2-(benzhydrylideneamino)acetonitrile Chemical compound C=1C=CC=CC=1C(=NCC#N)C1=CC=CC=C1 VRLJFRODHVSTIK-UHFFFAOYSA-N 0.000 description 1
- ARJOJUQBOMFBDN-UHFFFAOYSA-N 2-(bromomethyl)-1-benzofuran Chemical compound C1=CC=C2OC(CBr)=CC2=C1 ARJOJUQBOMFBDN-UHFFFAOYSA-N 0.000 description 1
- XLDDEDRHNNWHEQ-UHFFFAOYSA-N 2-(bromomethyl)-7-fluoronaphthalene Chemical compound C1=CC(CBr)=CC2=CC(F)=CC=C21 XLDDEDRHNNWHEQ-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
- MWEYJKVEIBBEJK-UHFFFAOYSA-N 2-amino-3-(3,4-dihydronaphthalen-2-yl)-2-methylpropanenitrile Chemical compound C1=CC=C2CCC(CC(N)(C)C#N)=CC2=C1 MWEYJKVEIBBEJK-UHFFFAOYSA-N 0.000 description 1
- MCCSHBZLJPBOID-UHFFFAOYSA-N 2-amino-3-(3,4-dihydronaphthalen-2-yl)propanenitrile Chemical compound C1=CC=C2CCC(CC(N)C#N)=CC2=C1 MCCSHBZLJPBOID-UHFFFAOYSA-N 0.000 description 1
- NRXLQUGZWMDFSB-UHFFFAOYSA-N 2-methyl-2-n-(1-phenylethyl)-3-(1,2,3,4-tetrahydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1CC2=CC=CC=C2CC1CC(C)(CN)NC(C)C1=CC=CC=C1 NRXLQUGZWMDFSB-UHFFFAOYSA-N 0.000 description 1
- YWTHCBZAHBGRPL-UHFFFAOYSA-N 2-methyl-3-(1,2,3,4-tetrahydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=CC=C2CC(CC(N)(CN)C)CCC2=C1 YWTHCBZAHBGRPL-UHFFFAOYSA-N 0.000 description 1
- OVTZQVVSWMGEDH-UHFFFAOYSA-N 3-(1,2,3,4-tetrahydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=CC=C2CC(CC(N)CN)CCC2=C1 OVTZQVVSWMGEDH-UHFFFAOYSA-N 0.000 description 1
- ATXKPXAYWBBUPA-UHFFFAOYSA-N 3-(2h-chromen-3-yl)propane-1,2-diamine Chemical compound C1=CC=C2OCC(CC(N)CN)=CC2=C1 ATXKPXAYWBBUPA-UHFFFAOYSA-N 0.000 description 1
- SVBBZJPYPMWSDU-UHFFFAOYSA-N 3-(3,4-dihydronaphthalen-2-yl)-2-methyl-2-(1-phenylethylamino)propanenitrile Chemical compound C=1C2=CC=CC=C2CCC=1CC(C)(C#N)NC(C)C1=CC=CC=C1 SVBBZJPYPMWSDU-UHFFFAOYSA-N 0.000 description 1
- IZBHJANDSVJYFR-UHFFFAOYSA-N 3-(3,4-dihydronaphthalen-2-yl)-2-methyl-2-n-(1-phenylethyl)propane-1,2-diamine Chemical compound C=1C2=CC=CC=C2CCC=1CC(C)(CN)NC(C)C1=CC=CC=C1 IZBHJANDSVJYFR-UHFFFAOYSA-N 0.000 description 1
- CLCPMUYEQUSIGG-UHFFFAOYSA-N 3-(3,4-dihydronaphthalen-2-yl)-2-methylpropane-1,2-diamine Chemical compound C1=CC=C2CCC(CC(N)(CN)C)=CC2=C1 CLCPMUYEQUSIGG-UHFFFAOYSA-N 0.000 description 1
- XFQNGHYQCQCYQA-UHFFFAOYSA-N 3-(3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=CC=C2CCC(CC(N)CN)=CC2=C1 XFQNGHYQCQCYQA-UHFFFAOYSA-N 0.000 description 1
- ABTFUUJSICETNO-UHFFFAOYSA-N 3-(6-methyl-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=C(CC(N)CN)CCC2=CC(C)=CC=C21 ABTFUUJSICETNO-UHFFFAOYSA-N 0.000 description 1
- GYUFIXALQGJWSG-UHFFFAOYSA-N 3-(7-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=C(F)C=C2CC(CC(N)CN)CCC2=C1 GYUFIXALQGJWSG-UHFFFAOYSA-N 0.000 description 1
- GWGPBRXLJIREAL-UHFFFAOYSA-N 3-(7-fluoro-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound FC1=CC=C2CCC(CC(N)CN)=CC2=C1 GWGPBRXLJIREAL-UHFFFAOYSA-N 0.000 description 1
- SIBCVZVOPLLICP-UHFFFAOYSA-N 3-(7-methoxy-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1CC(CC(N)CN)=CC2=CC(OC)=CC=C21 SIBCVZVOPLLICP-UHFFFAOYSA-N 0.000 description 1
- PTMQQFIDAOXRNJ-UHFFFAOYSA-N 3-(7-methyl-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1CC(CC(N)CN)=CC2=CC(C)=CC=C21 PTMQQFIDAOXRNJ-UHFFFAOYSA-N 0.000 description 1
- FVZGZMMVAJIXCC-UHFFFAOYSA-N 3-(8-chloro-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=CC=C2CCC(CC(N)CN)=CC2=C1Cl FVZGZMMVAJIXCC-UHFFFAOYSA-N 0.000 description 1
- INTCZRUIKONFLU-UHFFFAOYSA-N 3-(8-fluoro-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1=CC=C2CCC(CC(N)CN)=CC2=C1F INTCZRUIKONFLU-UHFFFAOYSA-N 0.000 description 1
- SZXIIVFTOXYSMF-UHFFFAOYSA-N 3-(8-methoxy-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1CC(CC(N)CN)=CC2=C1C=CC=C2OC SZXIIVFTOXYSMF-UHFFFAOYSA-N 0.000 description 1
- VOXVIFBXCZLKNB-UHFFFAOYSA-N 3-(8-methyl-3,4-dihydronaphthalen-2-yl)propane-1,2-diamine Chemical compound C1CC(CC(N)CN)=CC2=C1C=CC=C2C VOXVIFBXCZLKNB-UHFFFAOYSA-N 0.000 description 1
- CTESSZBSNQFERI-UHFFFAOYSA-N 3-[7-(trifluoromethyl)-3,4-dihydronaphthalen-2-yl]propane-1,2-diamine Chemical compound FC(F)(F)C1=CC=C2CCC(CC(N)CN)=CC2=C1 CTESSZBSNQFERI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- JBSYDIKKOAPATG-UHFFFAOYSA-N 4-methoxy-n-(4-methoxyphenyl)-n-methylaniline Chemical compound C1=CC(OC)=CC=C1N(C)C1=CC=C(OC)C=C1 JBSYDIKKOAPATG-UHFFFAOYSA-N 0.000 description 1
- OSJRTWXVMCRBKZ-UHFFFAOYSA-N 5,6-difluoro-2,3-dihydroinden-1-one Chemical compound C1=C(F)C(F)=CC2=C1C(=O)CC2 OSJRTWXVMCRBKZ-UHFFFAOYSA-N 0.000 description 1
- NGUVTJVYXPICNG-WLHGVMLRSA-N 5-(1a,2,3,7b-tetrahydro-1h-cyclopropa[a]naphthalen-1-ylmethyl)-4,5-dihydro-1h-imidazole;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C12CCC3=CC=CC=C3C2C1CC1CNC=N1 NGUVTJVYXPICNG-WLHGVMLRSA-N 0.000 description 1
- OOIBKWSVXJWTHR-UHFFFAOYSA-N 5-(2,3-dihydro-1h-inden-2-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound C1C2=CC=CC=C2CC1CC1CNC=N1 OOIBKWSVXJWTHR-UHFFFAOYSA-N 0.000 description 1
- AHXKOBNBPUNQDW-UHFFFAOYSA-N 5-(2h-chromen-3-ylmethyl)-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC=CC=C2OCC=1CC1CN=CN1 AHXKOBNBPUNQDW-UHFFFAOYSA-N 0.000 description 1
- LQJGPTUEUKGVLC-UHFFFAOYSA-N 5-[(4-fluoro-2,3-dihydro-1h-inden-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C1C=2C(F)=CC=CC=2CC1CC1CNC=N1 LQJGPTUEUKGVLC-UHFFFAOYSA-N 0.000 description 1
- YCZAOKJKYXRUAM-UHFFFAOYSA-N 5-[(5-chloro-2,3-dihydro-1h-inden-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C1C2=CC(Cl)=CC=C2CC1CC1CNC=N1 YCZAOKJKYXRUAM-UHFFFAOYSA-N 0.000 description 1
- RCZFCLUNYDMKFU-UHFFFAOYSA-N 5-[(5-fluoro-1-benzofuran-2-yl)methyl]-4,5-dihydro-1h-imidazole Chemical compound C=1C2=CC(F)=CC=C2OC=1CC1CN=CN1 RCZFCLUNYDMKFU-UHFFFAOYSA-N 0.000 description 1
- ZUGWHCSAAMHQKY-UHFFFAOYSA-N 7-(bromomethyl)-1-chloronaphthalene Chemical compound C1=C(CBr)C=C2C(Cl)=CC=CC2=C1 ZUGWHCSAAMHQKY-UHFFFAOYSA-N 0.000 description 1
- NQMQVBHBOBSOSZ-UHFFFAOYSA-N 7-fluoro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(F)=CC=C21 NQMQVBHBOBSOSZ-UHFFFAOYSA-N 0.000 description 1
- OMQCLLREZCFWBI-UHFFFAOYSA-N 7-fluoro-3,4-dihydronaphthalene-2-carbaldehyde Chemical compound C1CC(C=O)=CC2=CC(F)=CC=C21 OMQCLLREZCFWBI-UHFFFAOYSA-N 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- WDURDGSRVNNEDH-WLHGVMLRSA-N C(\C=C\C(=O)O)(=O)O.ClC=1C=CC=C2CCC(CC12)CC1N=CNC1 Chemical compound C(\C=C\C(=O)O)(=O)O.ClC=1C=CC=C2CCC(CC12)CC1N=CNC1 WDURDGSRVNNEDH-WLHGVMLRSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- UQABYHGXWYXDTK-UUOKFMHZSA-N GppNP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)NP(O)(O)=O)[C@@H](O)[C@H]1O UQABYHGXWYXDTK-UUOKFMHZSA-N 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 150000001907 coumarones Chemical class 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- WHFKIZXBVFEJGA-UHFFFAOYSA-L dihydroxy(dioxo)chromium;pyridine Chemical compound O[Cr](O)(=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 WHFKIZXBVFEJGA-UHFFFAOYSA-L 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- WEZNBTOFOKGBKQ-UHFFFAOYSA-N ethyl 2-(1,2,3,4-tetrahydronaphthalen-2-yl)acetate Chemical compound C1=CC=C2CC(CC(=O)OCC)CCC2=C1 WEZNBTOFOKGBKQ-UHFFFAOYSA-N 0.000 description 1
- COEGJEUVZAAECC-UHFFFAOYSA-N ethyl 2-(1h-inden-2-yl)acetate Chemical compound C1=CC=C2CC(CC(=O)OCC)=CC2=C1 COEGJEUVZAAECC-UHFFFAOYSA-N 0.000 description 1
- IBQXCEHAEYSYBT-UHFFFAOYSA-N ethyl 2-(3,4-dihydronaphthalen-2-yl)acetate Chemical compound C1=CC=C2CCC(CC(=O)OCC)=CC2=C1 IBQXCEHAEYSYBT-UHFFFAOYSA-N 0.000 description 1
- DTHLOQFFSAMPQS-UHFFFAOYSA-N ethyl 2-(6-methyl-3,4-dihydronaphthalen-2-yl)acetate Chemical compound C1=C(C)C=C2CCC(CC(=O)OCC)=CC2=C1 DTHLOQFFSAMPQS-UHFFFAOYSA-N 0.000 description 1
- WUDWYEKCWSNCJG-UHFFFAOYSA-N ethyl 2-(7-fluoro-3,4-dihydronaphthalen-2-yl)acetate Chemical compound FC1=CC=C2CCC(CC(=O)OCC)=CC2=C1 WUDWYEKCWSNCJG-UHFFFAOYSA-N 0.000 description 1
- BMBRXHIBRARXAE-UHFFFAOYSA-N ethyl 2-(7-methoxy-3,4-dihydronaphthalen-2-yl)acetate Chemical compound COC1=CC=C2CCC(CC(=O)OCC)=CC2=C1 BMBRXHIBRARXAE-UHFFFAOYSA-N 0.000 description 1
- AGVLEQGJNWPZOB-UHFFFAOYSA-N ethyl 2-(7-methyl-3,4-dihydronaphthalen-2-yl)acetate Chemical compound CC1=CC=C2CCC(CC(=O)OCC)=CC2=C1 AGVLEQGJNWPZOB-UHFFFAOYSA-N 0.000 description 1
- XWOKDQWBUYCFKW-UHFFFAOYSA-N ethyl 2-(8-fluoro-3,4-dihydronaphthalen-2-yl)acetate Chemical compound C1=CC=C2CCC(CC(=O)OCC)=CC2=C1F XWOKDQWBUYCFKW-UHFFFAOYSA-N 0.000 description 1
- FSFTXGONCNHTAO-UHFFFAOYSA-N ethyl 2-(8-methoxy-3,4-dihydronaphthalen-2-yl)acetate Chemical compound C1=CC=C(OC)C2=C1CCC(CC(=O)OCC)=C2 FSFTXGONCNHTAO-UHFFFAOYSA-N 0.000 description 1
- UVMXQTXMPUTDDI-UHFFFAOYSA-N ethyl 2-(8-methyl-3,4-dihydronaphthalen-2-yl)acetate Chemical compound C1=CC=C2CCC(CC(=O)OCC)=CC2=C1C UVMXQTXMPUTDDI-UHFFFAOYSA-N 0.000 description 1
- FJNFTFYMQIXBIE-UHFFFAOYSA-N ethyl 2-[7-(trifluoromethyl)-3,4-dihydronaphthalen-2-yl]acetate Chemical compound FC(F)(F)C1=CC=C2CCC(CC(=O)OCC)=CC2=C1 FJNFTFYMQIXBIE-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical compound C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229940126403 monoamine reuptake inhibitor Drugs 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
- 229960001999 phentolamine Drugs 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P3/04—Anorexiants; Antiobesity 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/06—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
- C07D233/08—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms
- C07D233/10—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/22—Radicals substituted by oxygen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Addiction (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9815999A FR2787451B1 (fr) | 1998-12-18 | 1998-12-18 | Nouveaux composes imidazoliniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (3)
Publication Number | Publication Date |
---|---|
NO996284D0 NO996284D0 (no) | 1999-12-17 |
NO996284L NO996284L (no) | 2000-06-19 |
NO314544B1 true NO314544B1 (no) | 2003-04-07 |
Family
ID=9534132
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19996284A NO314544B1 (no) | 1998-12-18 | 1999-12-17 | Nye imidazolinforbindelser, fremgangsmåte ved deres fremstilling og farmasöytiske sammensetninger inneholdende dem |
Country Status (22)
Country | Link |
---|---|
US (1) | US6127396A (ja) |
EP (1) | EP1010693B1 (ja) |
JP (1) | JP3526800B2 (ja) |
KR (1) | KR100492160B1 (ja) |
CN (1) | CN1183907C (ja) |
AT (1) | ATE250586T1 (ja) |
AU (1) | AU767856B2 (ja) |
BR (1) | BR9907497A (ja) |
CA (1) | CA2292927C (ja) |
DE (1) | DE69911557T2 (ja) |
DK (1) | DK1010693T3 (ja) |
EA (1) | EA004536B1 (ja) |
ES (1) | ES2209362T3 (ja) |
FR (1) | FR2787451B1 (ja) |
HK (1) | HK1027573A1 (ja) |
HU (1) | HUP9904628A3 (ja) |
NO (1) | NO314544B1 (ja) |
NZ (1) | NZ501785A (ja) |
PL (1) | PL202198B1 (ja) |
PT (1) | PT1010693E (ja) |
SI (1) | SI1010693T1 (ja) |
ZA (1) | ZA997734B (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA981080B (en) | 1997-02-11 | 1998-08-12 | Warner Lambert Co | Bicyclic inhibitors of protein farnesyl transferase |
US6559157B2 (en) | 1997-10-02 | 2003-05-06 | Daiichi Pharmaceutical Co., Ltd. | Dihydronaphthalene compounds |
NZ501822A (en) * | 1997-10-02 | 2001-12-21 | Yukijirushi Nyugyo Kabushiki K | Therapeutic agents for male and female sex hormone dependent diseases |
AU2001296542B2 (en) * | 2000-10-02 | 2007-10-25 | Emory University | Triptolide analogs for the treatment of autoimmune and inflammatory disorders |
BRPI0519013A2 (pt) * | 2004-12-13 | 2009-11-03 | Lilly Co Eli | composto ou esteroisÈmeros únicos, misturas de esteroisÈmeros, sais, tautÈmeros ou pró-drogas destes farmaceuticamente aceitáveis, composição farmacêutica, e, uso de um composto |
MX2009013745A (es) * | 2007-07-03 | 2010-01-26 | Hoffmann La Roche | 4-imidazolinas y su uso como antidepresivos. |
WO2009089285A2 (en) * | 2008-01-07 | 2009-07-16 | Emory University | Branched diepoxide compounds for the treatment of inflammatory disorders |
US20100298305A1 (en) * | 2008-11-26 | 2010-11-25 | The United States Government, As Represented By The Department Of Veterans Affairs | Tizanidine for the treatment of post-traumatic stress disorder and nightmares |
US8771391B2 (en) | 2011-02-22 | 2014-07-08 | Baker Hughes Incorporated | Methods of forming polycrystalline compacts |
JP6692162B2 (ja) * | 2014-01-17 | 2020-05-13 | キッセイ薬品工業株式会社 | α−置換グリシンアミド誘導体 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE23337T1 (de) * | 1982-12-23 | 1986-11-15 | Ici America Inc | Chromanverbindungen. |
US4540705A (en) * | 1983-03-14 | 1985-09-10 | Sterling Drug Inc. | Antidepressant imidazolines and related compounds |
FR2542738A1 (fr) * | 1983-03-18 | 1984-09-21 | Synthelabo | Indanyl-2 d2-imidazoline, procede pour la preparer, et compositions pharmaceutiques qui la contiennent |
DE3583900D1 (de) * | 1984-06-06 | 1991-10-02 | Abbott Lab | Adrenergische verbindungen. |
JPH01242571A (ja) * | 1988-03-22 | 1989-09-27 | Mitsui Petrochem Ind Ltd | イミダゾール誘導体の製造方法 |
US5151526A (en) * | 1990-10-11 | 1992-09-29 | The United States Of America As Represented By The Secretary Of The Army | 4-[1-(1-naphthalenyl)ethyl]-1H-imidazole, method of making and use as an anesthetic |
KR920008026A (ko) * | 1990-10-24 | 1992-05-27 | 오노 화아마슈티칼 캄파니 리미팃드 | 이소퀴놀리논 유도체 또는 이의 무독성 산부가염 또는 이의 수화물, 이의 제조방법 및 이를 포함하는 약제 조성물 |
AU5118493A (en) * | 1992-10-06 | 1994-04-26 | Tokyo Tanabe Company Limited | Aromatase inhibitor |
DE19605400A1 (de) * | 1996-02-14 | 1997-08-21 | Bayer Ag | Salze von Imidazolin-Derivaten |
FR2756560A1 (fr) * | 1996-12-04 | 1998-06-05 | Adir | Nouveaux derives de l'imidazoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
-
1998
- 1998-12-18 FR FR9815999A patent/FR2787451B1/fr not_active Expired - Fee Related
-
1999
- 1999-12-14 NZ NZ501785A patent/NZ501785A/xx not_active IP Right Cessation
- 1999-12-15 PL PL337196A patent/PL202198B1/pl not_active IP Right Cessation
- 1999-12-17 HU HU9904628A patent/HUP9904628A3/hu unknown
- 1999-12-17 US US09/466,716 patent/US6127396A/en not_active Expired - Fee Related
- 1999-12-17 ES ES99403190T patent/ES2209362T3/es not_active Expired - Lifetime
- 1999-12-17 BR BR9907497-4A patent/BR9907497A/pt not_active Application Discontinuation
- 1999-12-17 AU AU65290/99A patent/AU767856B2/en not_active Ceased
- 1999-12-17 CA CA002292927A patent/CA2292927C/fr not_active Expired - Fee Related
- 1999-12-17 NO NO19996284A patent/NO314544B1/no not_active IP Right Cessation
- 1999-12-17 EP EP99403190A patent/EP1010693B1/fr not_active Expired - Lifetime
- 1999-12-17 ZA ZA9907734A patent/ZA997734B/xx unknown
- 1999-12-17 AT AT99403190T patent/ATE250586T1/de not_active IP Right Cessation
- 1999-12-17 DK DK99403190T patent/DK1010693T3/da active
- 1999-12-17 EA EA199901050A patent/EA004536B1/ru not_active IP Right Cessation
- 1999-12-17 DE DE69911557T patent/DE69911557T2/de not_active Expired - Lifetime
- 1999-12-17 JP JP35859299A patent/JP3526800B2/ja not_active Expired - Fee Related
- 1999-12-17 CN CNB991261798A patent/CN1183907C/zh not_active Expired - Fee Related
- 1999-12-17 SI SI9930414T patent/SI1010693T1/xx unknown
- 1999-12-17 PT PT99403190T patent/PT1010693E/pt unknown
- 1999-12-18 KR KR10-1999-0058936A patent/KR100492160B1/ko not_active IP Right Cessation
-
2000
- 2000-10-24 HK HK00106742A patent/HK1027573A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2232154C2 (ru) | Замещенные производные имидазола, способ введения фармацевтической композиции и способ лечения на основе этих соединений | |
JPH0676386B2 (ja) | 新規(ベンゾシクロアルキル)アルキルアミン化合物 | |
US4818764A (en) | Imidazoline derivative and method of treating depression therewith | |
NO314544B1 (no) | Nye imidazolinforbindelser, fremgangsmåte ved deres fremstilling og farmasöytiske sammensetninger inneholdende dem | |
NO860285L (no) | Fremgangsmaate ved fremstilling av imidazolderivater. | |
EP0396620A1 (en) | AMINOMETHYLE-CHROMANE AND AMINOMETHYLE-THIOCHROMANE COMPOUNDS. | |
US4397860A (en) | Benzodioxanyl imidazoline compounds, compositions and use | |
WO2001051472A9 (en) | New imidazole derivatives | |
US5185364A (en) | Aminomethyl-chroman and -thiochroman compounds | |
US5140039A (en) | Aminomethyl-thiochroman compounds | |
KR100472522B1 (ko) | 스피로 이미다졸린 화합물, 이것의 제조방법 및 이것을 함유하는 약제학적 조성물 | |
MXPA99011732A (en) | Imidazoline compounds | |
US6107345A (en) | Benzocyclobutane compounds | |
MXPA99011774A (en) | New compounds of spyroimidazole | |
WO2010077586A1 (en) | N-(1-phenyl-2-arylethyl)-4,5-dihydro-3h-pyrrol-2-amine compounds as subtype selective modulators of alpha2b or alpha2b and alpha2c adrenoceptors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |