DE1206437B - Verfahren zur Herstellung von neuen 4-Aza-thioxanthenderivaten - Google Patents
Verfahren zur Herstellung von neuen 4-Aza-thioxanthenderivatenInfo
- Publication number
- DE1206437B DE1206437B DES77010A DES0077010A DE1206437B DE 1206437 B DE1206437 B DE 1206437B DE S77010 A DES77010 A DE S77010A DE S0077010 A DES0077010 A DE S0077010A DE 1206437 B DE1206437 B DE 1206437B
- Authority
- DE
- Germany
- Prior art keywords
- aza
- methyl
- solution
- general formula
- thioxanthene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 9
- GAAYPTPSHXSMEM-UHFFFAOYSA-N 5h-thiochromeno[2,3-b]pyridine Chemical class C1=CC=C2CC3=CC=CC=C3SC2=N1 GAAYPTPSHXSMEM-UHFFFAOYSA-N 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 25
- VEOSCXKPFWPNIA-UHFFFAOYSA-N thiochromeno[2,3-b]pyridin-5-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=N1 VEOSCXKPFWPNIA-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- LLRRMBKLTKUJGB-UHFFFAOYSA-N OC1C(C=CC=N2)=C2SC2=CC=CC=C12 Chemical class OC1C(C=CC=N2)=C2SC2=CC=CC=C12 LLRRMBKLTKUJGB-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 239000000155 melt Substances 0.000 description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- 238000001953 recrystallisation Methods 0.000 description 14
- 238000000354 decomposition reaction Methods 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002026 chloroform extract Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 229960001340 histamine Drugs 0.000 description 8
- 229910000861 Mg alloy Inorganic materials 0.000 description 7
- OWXLRKWPEIAGAT-UHFFFAOYSA-N [Mg].[Cu] Chemical compound [Mg].[Cu] OWXLRKWPEIAGAT-UHFFFAOYSA-N 0.000 description 7
- 239000001530 fumaric acid Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 6
- -1 1,3-dimethyl-9- (3'-dimethylamino-propylidene) -4-aza-thioxanthene hydrobromide Chemical compound 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- TXNDOVAHWNZRSV-UHFFFAOYSA-N CC1=CC(=NC=2SC3=CC=CC=C3C(C1=2)=O)C Chemical compound CC1=CC(=NC=2SC3=CC=CC=C3C(C1=2)=O)C TXNDOVAHWNZRSV-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- NLHXVNXTYWYVGB-UHFFFAOYSA-N 2-methylthiochromeno[2,3-b]pyridin-5-one Chemical compound C1=CC=C2C(=O)C3=CC=C(C)N=C3SC2=C1 NLHXVNXTYWYVGB-UHFFFAOYSA-N 0.000 description 4
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 4
- MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- 208000010513 Stupor Diseases 0.000 description 4
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 4
- 229960003750 ethyl chloride Drugs 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- JZSJMIGEMMHFPG-UHFFFAOYSA-N CC=1C=CC=2C(C3=CC=CC=C3SC=2N=1)=CCCN(C)C Chemical compound CC=1C=CC=2C(C3=CC=CC=C3SC=2N=1)=CCCN(C)C JZSJMIGEMMHFPG-UHFFFAOYSA-N 0.000 description 3
- RGLOUOVASVAHJD-UHFFFAOYSA-N CN(CCC=C1C2=CC=CC=C2SC=2N=CC=CC1=2)C Chemical compound CN(CCC=C1C2=CC=CC=C2SC=2N=CC=CC1=2)C RGLOUOVASVAHJD-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229940050176 methyl chloride Drugs 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VEXKIOOWPFOHQI-UHFFFAOYSA-N 1-(3-chloro-2-methylpropyl)piperidine Chemical compound ClCC(C)CN1CCCCC1 VEXKIOOWPFOHQI-UHFFFAOYSA-N 0.000 description 2
- JFRADIZADCTHAS-UHFFFAOYSA-N 4,6-dimethyl-2-phenylsulfanylpyridine-3-carboxylic acid Chemical compound CC1=CC(C)=C(C(O)=O)C(SC=2C=CC=CC=2)=N1 JFRADIZADCTHAS-UHFFFAOYSA-N 0.000 description 2
- LZFNEUKCJNVRPI-UHFFFAOYSA-N 4-chloro-n,n-dimethylbutan-2-amine Chemical compound CN(C)C(C)CCCl LZFNEUKCJNVRPI-UHFFFAOYSA-N 0.000 description 2
- XHFRWZHWRQHZET-UHFFFAOYSA-N 6-methyl-2-phenylsulfanylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(SC=2C=CC=CC=2)=N1 XHFRWZHWRQHZET-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 2
- PXAZNIZKQUWSIY-UHFFFAOYSA-N CC(C=C1C2=CC=CC=C2SC=2N=CC=CC1=2)CN1CCCCC1 Chemical compound CC(C=C1C2=CC=CC=C2SC=2N=CC=CC1=2)CN1CCCCC1 PXAZNIZKQUWSIY-UHFFFAOYSA-N 0.000 description 2
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 2
- 229960000396 atropine Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 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
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- AUERUDPETOKUPT-UHFFFAOYSA-N 1-(3-chloropropyl)-4-methylpiperazine Chemical compound CN1CCN(CCCCl)CC1 AUERUDPETOKUPT-UHFFFAOYSA-N 0.000 description 1
- HDDNBUNZJIQDBQ-UHFFFAOYSA-N 1-(3-chloropropyl)piperidine Chemical compound ClCCCN1CCCCC1 HDDNBUNZJIQDBQ-UHFFFAOYSA-N 0.000 description 1
- SPRTXTPFQKHSBG-UHFFFAOYSA-N 1-(3-chloropropyl)pyrrolidine Chemical compound ClCCCN1CCCC1 SPRTXTPFQKHSBG-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- RETJKTAVEQPNMH-UHFFFAOYSA-N 2-chloro-4,6-dimethylpyridine-3-carbonitrile Chemical compound CC1=CC(C)=C(C#N)C(Cl)=N1 RETJKTAVEQPNMH-UHFFFAOYSA-N 0.000 description 1
- YSBNBAYNISAUIT-UHFFFAOYSA-N 2-chloro-6-methylpyridine-3-carbonitrile Chemical compound CC1=CC=C(C#N)C(Cl)=N1 YSBNBAYNISAUIT-UHFFFAOYSA-N 0.000 description 1
- UPASYJUQYLIDMN-UHFFFAOYSA-N 3-bromo-n,n-diethylpropan-1-amine Chemical compound CCN(CC)CCCBr UPASYJUQYLIDMN-UHFFFAOYSA-N 0.000 description 1
- WVUULNDRFBHTFG-UHFFFAOYSA-N 3-chloro-n,n-diethylpropan-1-amine Chemical compound CCN(CC)CCCCl WVUULNDRFBHTFG-UHFFFAOYSA-N 0.000 description 1
- QUQQIOJAMADCQH-UHFFFAOYSA-N 4,6-dimethyl-2-phenylsulfanylpyridine-3-carbonitrile Chemical compound CC1=CC(C)=C(C#N)C(SC=2C=CC=CC=2)=N1 QUQQIOJAMADCQH-UHFFFAOYSA-N 0.000 description 1
- FMSFNNYIVOBMQX-UHFFFAOYSA-N 4-(3-thiochromeno[2,3-b]pyridin-5-ylidenepropyl)morpholine Chemical compound O1CCN(CC1)CCC=C1C2=CC=CC=C2SC=2N=CC=CC1=2 FMSFNNYIVOBMQX-UHFFFAOYSA-N 0.000 description 1
- VOUGRVOMTRTALH-UHFFFAOYSA-N 5-(3-pyrrolidin-1-ylpropylidene)thiochromeno[2,3-b]pyridine Chemical compound N1(CCCC1)CCC=C1C2=CC=CC=C2SC=2N=CC=CC1=2 VOUGRVOMTRTALH-UHFFFAOYSA-N 0.000 description 1
- RJVUMWAHFPCWAB-UHFFFAOYSA-N 6-methyl-2-phenylsulfanylpyridine-3-carbonitrile Chemical compound CC1=CC=C(C#N)C(SC=2C=CC=CC=2)=N1 RJVUMWAHFPCWAB-UHFFFAOYSA-N 0.000 description 1
- FBEHFRAORPEGFH-UHFFFAOYSA-N Allyxycarb Chemical compound CNC(=O)OC1=CC(C)=C(N(CC=C)CC=C)C(C)=C1 FBEHFRAORPEGFH-UHFFFAOYSA-N 0.000 description 1
- QHGRBHGRDGBKCN-UHFFFAOYSA-N C(#N)C=1C=CC(=NC=1C1=CC=CC=C1)S Chemical class C(#N)C=1C=CC(=NC=1C1=CC=CC=C1)S QHGRBHGRDGBKCN-UHFFFAOYSA-N 0.000 description 1
- KRILPCJHEFOBPO-UHFFFAOYSA-N CC1=CC(=NC=2SC3=CC=CC=C3C(C1=2)=CCCN(C)C)C Chemical compound CC1=CC(=NC=2SC3=CC=CC=C3C(C1=2)=CCCN(C)C)C KRILPCJHEFOBPO-UHFFFAOYSA-N 0.000 description 1
- ZJKDRVIJAXHKNU-UHFFFAOYSA-N CC1=NC(=C(C(=C1S)C)C#N)C1=CC=CC=C1 Chemical compound CC1=NC(=C(C(=C1S)C)C#N)C1=CC=CC=C1 ZJKDRVIJAXHKNU-UHFFFAOYSA-N 0.000 description 1
- ZLUPATAUKYGTRD-UHFFFAOYSA-N CN(C(CC=C1C2=CC=CC=C2SC=2N=CC=CC1=2)C)C Chemical compound CN(C(CC=C1C2=CC=CC=C2SC=2N=CC=CC1=2)C)C ZLUPATAUKYGTRD-UHFFFAOYSA-N 0.000 description 1
- WAERFHZVEBCOBV-UHFFFAOYSA-N CN1CCN(CCC=C2C(C=CC=N3)=C3SC3=CC=CC=C23)CC1 Chemical compound CN1CCN(CCC=C2C(C=CC=N3)=C3SC3=CC=CC=C23)CC1 WAERFHZVEBCOBV-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- RSKHVRQAEPYNLV-UHFFFAOYSA-N N1(CCCCC1)CCC=C1C2=CC=CC=C2SC=2N=CC=CC1=2 Chemical compound N1(CCCCC1)CCC=C1C2=CC=CC=C2SC=2N=CC=CC1=2 RSKHVRQAEPYNLV-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
- 230000002908 adrenolytic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- DLAKWHKNGHJWKA-UHFFFAOYSA-N pacatal Chemical compound C1CN(C)CCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 DLAKWHKNGHJWKA-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940043200 pentothal Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000004634 pharmacological analysis method Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1375760A CH387638A (de) | 1960-12-08 | 1960-12-08 | Verfahren zur Herstellung von neuen heterocyclischen Verbindungen |
| CH1083561 | 1961-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1206437B true DE1206437B (de) | 1965-12-09 |
Family
ID=25707343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DES77010A Pending DE1206437B (de) | 1960-12-08 | 1961-12-06 | Verfahren zur Herstellung von neuen 4-Aza-thioxanthenderivaten |
Country Status (4)
| Country | Link |
|---|---|
| DE (1) | DE1206437B (cs) |
| ES (1) | ES272728A1 (cs) |
| GB (1) | GB1003292A (cs) |
| LU (1) | LU40916A1 (cs) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8058287B2 (en) | 2001-11-21 | 2011-11-15 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US8394817B2 (en) | 2002-11-13 | 2013-03-12 | Millennium Pharmaceuticals, Inc. | CCR1 antagonists and methods of use therefor |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1049700B9 (en) | 1998-01-21 | 2006-05-10 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| AU2335699A (en) | 1998-01-21 | 1999-08-09 | Kyowa Hakko Kogyo Co. Ltd. | Chemokine receptor antagonists and methods of use therefor |
| US6509346B2 (en) | 1998-01-21 | 2003-01-21 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6613905B1 (en) | 1998-01-21 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US7271176B2 (en) | 1998-09-04 | 2007-09-18 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use thereof |
-
1961
- 1961-11-13 GB GB4046361A patent/GB1003292A/en not_active Expired
- 1961-12-06 LU LU40916A patent/LU40916A1/xx unknown
- 1961-12-06 ES ES0272728A patent/ES272728A1/es not_active Expired
- 1961-12-06 DE DES77010A patent/DE1206437B/de active Pending
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8058287B2 (en) | 2001-11-21 | 2011-11-15 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US8653096B2 (en) | 2001-11-21 | 2014-02-18 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use thereof |
| US9663537B2 (en) | 2001-11-21 | 2017-05-30 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use |
| US8394817B2 (en) | 2002-11-13 | 2013-03-12 | Millennium Pharmaceuticals, Inc. | CCR1 antagonists and methods of use therefor |
| US9334283B2 (en) | 2002-11-13 | 2016-05-10 | Millennium Pharmaceuticals, Inc. | CCR1 antagonists and methods of use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| ES272728A1 (es) | 1962-07-01 |
| LU40916A1 (cs) | 1962-06-06 |
| GB1003292A (en) | 1965-09-02 |
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