NO301327B1 - Tienocyklopentanonoksimetere, og farmasöytiske blandinger som inneholder dem - Google Patents
Tienocyklopentanonoksimetere, og farmasöytiske blandinger som inneholder dem Download PDFInfo
- Publication number
- NO301327B1 NO301327B1 NO923720A NO923720A NO301327B1 NO 301327 B1 NO301327 B1 NO 301327B1 NO 923720 A NO923720 A NO 923720A NO 923720 A NO923720 A NO 923720A NO 301327 B1 NO301327 B1 NO 301327B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- alkyl
- acid
- thiophene
- ether
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 64
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 21
- 229930192474 thiophene Natural products 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- -1 pyridylethyl Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 5
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000003544 oxime group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000002023 wood Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 98
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000000034 method Methods 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 239000003921 oil Substances 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 20
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 19
- 150000002576 ketones Chemical class 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000155 melt Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 150000002923 oximes Chemical class 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 11
- ZYQZCLMECLFQGS-UHFFFAOYSA-N n-[4-(2-chlorophenyl)-4,5-dihydrocyclopenta[b]thiophen-6-ylidene]hydroxylamine Chemical compound C1=2C=CSC=2C(=NO)CC1C1=CC=CC=C1Cl ZYQZCLMECLFQGS-UHFFFAOYSA-N 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 229940076279 serotonin Drugs 0.000 description 10
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 238000004821 distillation Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 229920000137 polyphosphoric acid Polymers 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 102000035037 5-HT3 receptors Human genes 0.000 description 5
- 108091005477 5-HT3 receptors Proteins 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 5
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 5
- 235000005513 chalcones Nutrition 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 235000006408 oxalic acid Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 150000001789 chalcones Chemical class 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 4
- 229960003708 sumatriptan Drugs 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VJFIKJAVIOUTJF-UHFFFAOYSA-N C1C(=NO)C=2SC=CC=2C1(C)C1=CC=CC=C1 Chemical compound C1C(=NO)C=2SC=CC=2C1(C)C1=CC=CC=C1 VJFIKJAVIOUTJF-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 101100321769 Takifugu rubripes htr1d gene Proteins 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 2
- OCWDBKQNNKCYCJ-UHFFFAOYSA-N 2-(2-bromoethoxy)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(OCCBr)C(=O)C2=C1 OCWDBKQNNKCYCJ-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- OUQWQGRWZXKIFA-UHFFFAOYSA-N 3-(2-chlorophenyl)-3-thiophen-3-ylbutanoic acid Chemical compound C=1C=CC=C(Cl)C=1C(CC(O)=O)(C)C=1C=CSC=1 OUQWQGRWZXKIFA-UHFFFAOYSA-N 0.000 description 2
- NZNFXNFHUHGWMW-UHFFFAOYSA-N 4-(2-chlorophenyl)-4,5-dihydrocyclopenta[b]thiophen-6-one Chemical compound ClC1=CC=CC=C1C1C(C=CS2)=C2C(=O)C1 NZNFXNFHUHGWMW-UHFFFAOYSA-N 0.000 description 2
- DXJUVXMGPQMHSS-UHFFFAOYSA-N 4-(2-chlorophenyl)-4-methyl-5h-cyclopenta[b]thiophen-6-one Chemical compound C1C(=O)C=2SC=CC=2C1(C)C1=CC=CC=C1Cl DXJUVXMGPQMHSS-UHFFFAOYSA-N 0.000 description 2
- 101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 101000783611 Takifugu rubripes 5-hydroxytryptamine receptor 1D Proteins 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- LKHXNASBOCWBNT-UHFFFAOYSA-N ethyl 2-cyano-3-thiophen-3-ylbut-2-enoate Chemical compound CCOC(=O)C(C#N)=C(C)C=1C=CSC=1 LKHXNASBOCWBNT-UHFFFAOYSA-N 0.000 description 2
- FYCFQDDCKKIWFG-UHFFFAOYSA-N ethyl 3-(2-chlorophenyl)-2-cyano-3-thiophen-3-ylbutanoate Chemical compound C=1C=CC=C(Cl)C=1C(C)(C(C#N)C(=O)OCC)C=1C=CSC=1 FYCFQDDCKKIWFG-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 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
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- SDTURPIJJOEFIR-UHFFFAOYSA-N 1-bromo-2-ethynylbenzene;dithiophen-2-ylmethanone Chemical compound BrC1=CC=CC=C1C#C.C=1C=CSC=1C(=O)C1=CC=CS1 SDTURPIJJOEFIR-UHFFFAOYSA-N 0.000 description 1
- INFQENFEYWXPCF-UHFFFAOYSA-N 1-chloro-2-ethynylbenzene;dithiophen-2-ylmethanone Chemical compound ClC1=CC=CC=C1C#C.C=1C=CSC=1C(=O)C1=CC=CS1 INFQENFEYWXPCF-UHFFFAOYSA-N 0.000 description 1
- ZNRGQMMCGHDTEI-UHFFFAOYSA-N 1H-indole-3-carboxylic acid (8-methyl-8-azabicyclo[3.2.1]octan-3-yl) ester Chemical compound C1=CC=C2C(C(=O)OC3CC4CCC(C3)N4C)=CNC2=C1 ZNRGQMMCGHDTEI-UHFFFAOYSA-N 0.000 description 1
- PTAPBGKYBVWNJY-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid;hydrate Chemical compound O.C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 PTAPBGKYBVWNJY-UHFFFAOYSA-N 0.000 description 1
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- RNIDWJDZNNVFDY-UHFFFAOYSA-N 3-Acetylthiophene Chemical compound CC(=O)C=1C=CSC=1 RNIDWJDZNNVFDY-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
- LKHHEMHSIKGIBO-UHFFFAOYSA-N 3-ethylpent-2-enoic acid Chemical compound CCC(CC)=CC(O)=O LKHHEMHSIKGIBO-UHFFFAOYSA-N 0.000 description 1
- GSNVIFNNUJYSOM-UHFFFAOYSA-N 3-thiophen-2-yl-3-thiophen-3-ylpropanoic acid Chemical compound C=1C=CSC=1C(CC(=O)O)C=1C=CSC=1 GSNVIFNNUJYSOM-UHFFFAOYSA-N 0.000 description 1
- IKHMCNNBUMMVAR-UHFFFAOYSA-N 4,4-diethyl-5h-cyclopenta[b]thiophen-6-one Chemical compound S1C=CC2=C1C(=O)CC2(CC)CC IKHMCNNBUMMVAR-UHFFFAOYSA-N 0.000 description 1
- XPIPCVDTXVLPEC-UHFFFAOYSA-N 4,4-dimethyl-5h-cyclopenta[b]thiophen-6-one Chemical compound S1C=CC2=C1C(=O)CC2(C)C XPIPCVDTXVLPEC-UHFFFAOYSA-N 0.000 description 1
- GLNMBYYMMAKWRB-UHFFFAOYSA-N 4-methyl-4-phenyl-5h-cyclopenta[b]thiophen-6-one Chemical compound C1C(=O)C=2SC=CC=2C1(C)C1=CC=CC=C1 GLNMBYYMMAKWRB-UHFFFAOYSA-N 0.000 description 1
- DTNKPLOOJKDKHR-UHFFFAOYSA-N 4-thiophen-2-yl-4,5-dihydrocyclopenta[b]thiophen-6-one Chemical compound C1=2C=CSC=2C(=O)CC1C1=CC=CS1 DTNKPLOOJKDKHR-UHFFFAOYSA-N 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- KRVMLPUDAOWOGN-UHFFFAOYSA-N 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole Chemical compound C12=CC(OC)=CC=C2NC=C1C1=CCNCC1 KRVMLPUDAOWOGN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- JRTOTLFJWDIMBF-UHFFFAOYSA-N C1=2C=CSC=2C(=NO)CC1C1=CC=CC=C1Br Chemical compound C1=2C=CSC=2C(=NO)CC1C1=CC=CC=C1Br JRTOTLFJWDIMBF-UHFFFAOYSA-N 0.000 description 1
- FBWKIRHCHGWVQQ-UHFFFAOYSA-N C1=2C=CSC=2C(=NO)CC1C1=CC=CC=C1O Chemical compound C1=2C=CSC=2C(=NO)CC1C1=CC=CC=C1O FBWKIRHCHGWVQQ-UHFFFAOYSA-N 0.000 description 1
- VFTQTCHGTMPEFC-UHFFFAOYSA-N C1C(=NO)C=2SC=CC=2C1(C)C1=CC=CC=C1Br Chemical compound C1C(=NO)C=2SC=CC=2C1(C)C1=CC=CC=C1Br VFTQTCHGTMPEFC-UHFFFAOYSA-N 0.000 description 1
- ATWHDNBSHDHNKD-UHFFFAOYSA-N C1C(=NO)C=2SC=CC=2C1(C)C1=CC=CC=C1Cl Chemical compound C1C(=NO)C=2SC=CC=2C1(C)C1=CC=CC=C1Cl ATWHDNBSHDHNKD-UHFFFAOYSA-N 0.000 description 1
- VFTITQNIOQBZEB-UHFFFAOYSA-N CC1=CC=CC=C1C1(C)C(C=CS2)=C2C(=NO)C1 Chemical compound CC1=CC=CC=C1C1(C)C(C=CS2)=C2C(=NO)C1 VFTITQNIOQBZEB-UHFFFAOYSA-N 0.000 description 1
- QQKBXHMRENJMJD-UHFFFAOYSA-N COC1=CC=CC=C1C1C(C=CS2)=C2C(=NO)C1 Chemical compound COC1=CC=CC=C1C1C(C=CS2)=C2C(=NO)C1 QQKBXHMRENJMJD-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- LVAHDXRVMCSGPT-UHFFFAOYSA-N S1C=CC2=C1C(=NO)CC2(C)C Chemical compound S1C=CC2=C1C(=NO)CC2(C)C LVAHDXRVMCSGPT-UHFFFAOYSA-N 0.000 description 1
- 229910006130 SO4 Inorganic materials 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000001253 acrylic acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002539 anti-aggressive effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002460 anti-migrenic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- NTBIYBAYFBNTCD-UHFFFAOYSA-N dibenzoyl 2,3-dihydroxybutanedioate Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- HULZRAVBXKKDEB-UHFFFAOYSA-N ethyl 3-ethylpent-2-enoate Chemical compound CCOC(=O)C=C(CC)CC HULZRAVBXKKDEB-UHFFFAOYSA-N 0.000 description 1
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- QBRSFUSGKXVSPM-UHFFFAOYSA-N hydroxylamine;hydrobromide Chemical compound Br.ON QBRSFUSGKXVSPM-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- AFTJOFXSFAYJNY-UHFFFAOYSA-N n-[4-(4-methylphenyl)-4,5-dihydrocyclopenta[b]thiophen-6-ylidene]hydroxylamine Chemical compound C1=CC(C)=CC=C1C1C(C=CS2)=C2C(=NO)C1 AFTJOFXSFAYJNY-UHFFFAOYSA-N 0.000 description 1
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- HFMLWSMSMPBTFE-UHFFFAOYSA-N o-(2-bromoethyl)hydroxylamine;hydrobromide Chemical compound Br.NOCCBr HFMLWSMSMPBTFE-UHFFFAOYSA-N 0.000 description 1
- NVYCCEFGRXBFOK-UHFFFAOYSA-N o-[2-(dimethylamino)ethyl]hydroxylamine Chemical compound CN(C)CCON NVYCCEFGRXBFOK-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002901 organomagnesium compounds Chemical class 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 238000006146 oximation reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000005543 phthalimide group Chemical class 0.000 description 1
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000001003 psychopharmacologic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/08—Hydrogen atoms or radicals containing only hydrogen and carbon atoms
- C07D333/10—Thiophene
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- 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
- 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
- C07D409/12—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 chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9111822 | 1991-09-25 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO923720D0 NO923720D0 (no) | 1992-09-24 |
| NO923720L NO923720L (no) | 1993-03-26 |
| NO301327B1 true NO301327B1 (no) | 1997-10-13 |
Family
ID=9417295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO923720A NO301327B1 (no) | 1991-09-25 | 1992-09-24 | Tienocyklopentanonoksimetere, og farmasöytiske blandinger som inneholder dem |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US5252749A (ko) |
| EP (1) | EP0534856B1 (ko) |
| JP (1) | JP3162822B2 (ko) |
| KR (1) | KR100199848B1 (ko) |
| AR (1) | AR248275A1 (ko) |
| AT (1) | ATE157360T1 (ko) |
| AU (1) | AU652072B2 (ko) |
| BR (1) | BR9203744A (ko) |
| CA (1) | CA2079016A1 (ko) |
| CZ (1) | CZ281936B6 (ko) |
| DE (1) | DE69221802T2 (ko) |
| DK (1) | DK0534856T3 (ko) |
| ES (1) | ES2108098T3 (ko) |
| FI (1) | FI106458B (ko) |
| GR (1) | GR3025335T3 (ko) |
| HU (1) | HU218204B (ko) |
| IL (1) | IL103106A (ko) |
| MX (1) | MX9205390A (ko) |
| NO (1) | NO301327B1 (ko) |
| NZ (1) | NZ244452A (ko) |
| PH (1) | PH30225A (ko) |
| RU (1) | RU2060253C1 (ko) |
| ZA (1) | ZA927318B (ko) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997044062A1 (en) * | 1996-05-23 | 1997-11-27 | Alcon Laboratories, Inc. | The use of 5-ht1b/1d agonists to treat ocular pain |
| WO2003014107A1 (en) * | 2001-08-01 | 2003-02-20 | Basell Polyolefine Gmbh | Process for the preparation of heterocyclic pentalene derivatives |
| US7432328B2 (en) * | 2005-06-14 | 2008-10-07 | Univation Technologies, Llc | Enhanced ESCR bimodal HDPE for blow molding applications |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE371190B (ko) * | 1972-03-24 | 1974-11-11 | Kabi Ab | |
| US3301874A (en) * | 1963-12-26 | 1967-01-31 | Sam Joseph | Thienocyclopentanone antibacterial agents |
| SE371193B (ko) * | 1972-03-24 | 1974-11-11 | Kabi Ab | |
| US4154740A (en) * | 1976-03-23 | 1979-05-15 | American Cyanamid Company | Substituted tetrahydrobenzothiophenes and method of preparation thereof |
| FR2471980A1 (fr) * | 1979-12-21 | 1981-06-26 | Sanofi Sa | Nouveaux derives de l'amino-1 propanol-2, leur procede de preparation et leur application therapeutique |
| FR2567125B1 (fr) * | 1984-07-09 | 1986-12-05 | Lipha | Acides dihydro-5,6-4h-cyclopenta (b) thiophenecarboxylique-6, procedes de preparation et medicaments les contenant |
| FR2639942B1 (fr) * | 1988-12-02 | 1991-03-29 | Sanofi Sa | Ethers oximes de propenone, procede pour leur preparation et compositions pharmaceutiques les contenant |
-
1992
- 1992-09-08 IL IL103106A patent/IL103106A/en not_active IP Right Cessation
- 1992-09-09 PH PH44908A patent/PH30225A/en unknown
- 1992-09-16 AU AU24548/92A patent/AU652072B2/en not_active Ceased
- 1992-09-22 AR AR92323223A patent/AR248275A1/es active
- 1992-09-23 US US07/954,530 patent/US5252749A/en not_active Expired - Fee Related
- 1992-09-23 MX MX9205390A patent/MX9205390A/es not_active IP Right Cessation
- 1992-09-23 CZ CS922918A patent/CZ281936B6/cs not_active IP Right Cessation
- 1992-09-23 NZ NZ244452A patent/NZ244452A/en unknown
- 1992-09-24 FI FI924281A patent/FI106458B/fi active
- 1992-09-24 ZA ZA927318A patent/ZA927318B/xx unknown
- 1992-09-24 NO NO923720A patent/NO301327B1/no not_active IP Right Cessation
- 1992-09-24 HU HU9203050A patent/HU218204B/hu not_active IP Right Cessation
- 1992-09-24 JP JP25506992A patent/JP3162822B2/ja not_active Expired - Fee Related
- 1992-09-24 ES ES92402627T patent/ES2108098T3/es not_active Expired - Lifetime
- 1992-09-24 DE DE69221802T patent/DE69221802T2/de not_active Expired - Fee Related
- 1992-09-24 RU SU925052821A patent/RU2060253C1/ru active
- 1992-09-24 CA CA002079016A patent/CA2079016A1/en not_active Abandoned
- 1992-09-24 DK DK92402627.1T patent/DK0534856T3/da active
- 1992-09-24 EP EP92402627A patent/EP0534856B1/fr not_active Expired - Lifetime
- 1992-09-24 AT AT92402627T patent/ATE157360T1/de not_active IP Right Cessation
- 1992-09-25 BR BR9203744A patent/BR9203744A/pt not_active Application Discontinuation
- 1992-09-25 KR KR1019920017585A patent/KR100199848B1/ko not_active IP Right Cessation
-
1997
- 1997-11-11 GR GR970402977T patent/GR3025335T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CZ291892A3 (en) | 1993-04-14 |
| JP3162822B2 (ja) | 2001-05-08 |
| MX9205390A (es) | 1993-05-01 |
| RU2060253C1 (ru) | 1996-05-20 |
| BR9203744A (pt) | 1994-03-29 |
| PH30225A (en) | 1997-02-05 |
| ZA927318B (en) | 1994-03-24 |
| FI924281A (fi) | 1993-03-26 |
| CZ281936B6 (cs) | 1997-04-16 |
| FI106458B (fi) | 2001-02-15 |
| EP0534856B1 (fr) | 1997-08-27 |
| JPH05213932A (ja) | 1993-08-24 |
| GR3025335T3 (en) | 1998-02-27 |
| HU9203050D0 (en) | 1992-12-28 |
| EP0534856A1 (fr) | 1993-03-31 |
| US5252749A (en) | 1993-10-12 |
| NO923720L (no) | 1993-03-26 |
| IL103106A0 (en) | 1993-02-21 |
| IL103106A (en) | 1998-06-15 |
| NO923720D0 (no) | 1992-09-24 |
| DE69221802T2 (de) | 1998-04-02 |
| KR100199848B1 (ko) | 1999-06-15 |
| DE69221802D1 (de) | 1997-10-02 |
| DK0534856T3 (da) | 1998-04-20 |
| AU2454892A (en) | 1993-04-01 |
| ES2108098T3 (es) | 1997-12-16 |
| HUT62876A (en) | 1993-06-28 |
| KR930006001A (ko) | 1993-04-20 |
| HU218204B (hu) | 2000-06-28 |
| AU652072B2 (en) | 1994-08-11 |
| FI924281A0 (fi) | 1992-09-24 |
| NZ244452A (en) | 1994-08-26 |
| ATE157360T1 (de) | 1997-09-15 |
| CA2079016A1 (en) | 1993-03-26 |
| AR248275A1 (es) | 1995-07-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60207406T2 (de) | Heteroaryloxy 3-substituierte propanamine s serotonin und norepinephrin reuptake-inhibitoren | |
| PL181165B1 (pl) | Pochodne podstawionego chromanu, sposób ich wytwarzania oraz preparat farmaceutyczny | |
| RU2092483C1 (ru) | Производные хромана или тиохромана и способы их получения (варианты) | |
| JPH08506823A (ja) | アザ環式化合物、該化合物を含む組成物及びタキキニン拮抗剤としての該化合物の使用 | |
| CZ393999A3 (cs) | Způsob přípravy farmaceuticky účinné látky | |
| JPH02262552A (ja) | プロペノンオキシムエーテル類、その製造方法、並びにこれを含有する調剤組成物 | |
| JP2001521529A (ja) | 置換へテロ芳香環５−ｈｔ▲下１ｆ▼アゴニスト | |
| JPH09512542A (ja) | Ｄ▲下４▼リセプタ拮抗剤としてのベンゾフラン誘導体 | |
| JP2001512727A (ja) | ５ｈｔ−１受容体のリガンドとしてのニ環式化合物 | |
| CZ256090A3 (cs) | Derivát v poloze 8-substituovaného 2-aminotetralinu, způsoby jeho přípravy, farmaceutický prostředek s jeho obsahem a použití | |
| DE69736890T2 (de) | Kondensierte heterozyklische verbindungen und ihre pharmazeutische anwendung | |
| JP2002511883A (ja) | ベンゾチオフェン誘導体ならびに対応する使用および組成物 | |
| BR112013007073B1 (pt) | Derivados do cromeno; composição farmacêutica; utilização de um composto da fórmula i e processo de preparação de um composto da fórmula i | |
| WO2003006455A1 (en) | Pharmaceutical compounds with serotonin receptor activity | |
| NO301327B1 (no) | Tienocyklopentanonoksimetere, og farmasöytiske blandinger som inneholder dem | |
| JP2003505457A (ja) | インドール誘導体 | |
| JPH0337549B2 (ko) | ||
| US3503990A (en) | 6-aryl-4,5,6,7-tetrahydro-4-oxoindole derivatives | |
| JP2002537288A (ja) | ドーパミンｄ１受容体アゴニスト化合物 | |
| JP3034556B2 (ja) | 医薬用化合物類 | |
| JP2003502411A (ja) | 神経保護剤としての１，４−ジアザシクロヘプタン誘導体 | |
| TW202306952A (zh) | 含三并環類衍生物調節劑、其製備方法和應用 | |
| JP2002533447A (ja) | 神経疾患の治療に有用な１，４−ジアザシクロヘプタン誘導体 | |
| JP2002533449A (ja) | 選択的エモパミル阻害剤としてのホモピペラジン誘導体 | |
| CZ2000947A3 (cs) | Substituované chromanové deriváty |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN MARCH 2002 |