CA1281328C - Piperazines disubstituees - Google Patents
Piperazines disubstitueesInfo
- Publication number
- CA1281328C CA1281328C CA000537834A CA537834A CA1281328C CA 1281328 C CA1281328 C CA 1281328C CA 000537834 A CA000537834 A CA 000537834A CA 537834 A CA537834 A CA 537834A CA 1281328 C CA1281328 C CA 1281328C
- Authority
- CA
- Canada
- Prior art keywords
- ethyl
- piperazine
- chlorophenyl
- formula
- salt
- 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.)
- Expired - Lifetime
Links
- 150000004885 piperazines Chemical class 0.000 title abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 83
- -1 C1-C7-alkoxy Chemical group 0.000 claims abstract description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 41
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 32
- 150000002367 halogens Chemical group 0.000 claims abstract description 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims abstract description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 116
- 238000000034 method Methods 0.000 claims description 45
- 238000004519 manufacturing process Methods 0.000 claims description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- 239000000460 chlorine Substances 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 14
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 12
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- ITRWZFVGJDQZIU-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=C1 ITRWZFVGJDQZIU-UHFFFAOYSA-N 0.000 claims description 3
- IPBRFUZGLJYPAG-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 IPBRFUZGLJYPAG-UHFFFAOYSA-N 0.000 claims description 3
- FNGMUJOECSGYTE-UHFFFAOYSA-N (2-aminophenyl)-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound NC1=CC=CC=C1C(=O)N1CCN(CCC=2C=CC=CC=2)CC1 FNGMUJOECSGYTE-UHFFFAOYSA-N 0.000 claims description 2
- SDRIGNBTIPFMOU-UHFFFAOYSA-N (2-aminophenyl)-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound NC1=CC=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 SDRIGNBTIPFMOU-UHFFFAOYSA-N 0.000 claims description 2
- UPWQKCPUOBLXET-UHFFFAOYSA-N (3,4-dimethoxyphenyl)-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(CCC=2C=CC=CC=2)CC1 UPWQKCPUOBLXET-UHFFFAOYSA-N 0.000 claims description 2
- LVQXLRHYRDUDGT-UHFFFAOYSA-N (3,4-dimethoxyphenyl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(CCC=2C=CC(F)=CC=2)CC1 LVQXLRHYRDUDGT-UHFFFAOYSA-N 0.000 claims description 2
- ZUPJTGGTBHOUFJ-UHFFFAOYSA-N (3-methoxyphenyl)-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound COC1=CC=CC(C(=O)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 ZUPJTGGTBHOUFJ-UHFFFAOYSA-N 0.000 claims description 2
- ZSBOQEHCUSDKIK-UHFFFAOYSA-N (3-methoxyphenyl)-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C(=O)C=2C=C(OC)C=CC=2)CC1 ZSBOQEHCUSDKIK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- OKQCKIJAEKZGKF-UHFFFAOYSA-N [4-[2-(3-chlorophenyl)ethyl]piperazin-1-yl]-(3,4-dimethoxyphenyl)methanone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(CCC=2C=C(Cl)C=CC=2)CC1 OKQCKIJAEKZGKF-UHFFFAOYSA-N 0.000 claims description 2
- UZBMPRCGMGQYOA-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2-methoxyphenyl)methanone Chemical compound COC1=CC=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 UZBMPRCGMGQYOA-UHFFFAOYSA-N 0.000 claims description 2
- JRZOORQRAQDSNQ-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(3,4-dimethoxyphenyl)methanone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 JRZOORQRAQDSNQ-UHFFFAOYSA-N 0.000 claims description 2
- YPLSFHBFZLTZQF-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(3,5-dimethoxyphenyl)methanone Chemical compound COC1=CC(OC)=CC(C(=O)N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=C1 YPLSFHBFZLTZQF-UHFFFAOYSA-N 0.000 claims description 2
- CJZHOJARNOFKGY-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 CJZHOJARNOFKGY-UHFFFAOYSA-N 0.000 claims description 2
- XTQLJIHMIOXTMS-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-[4-(dimethylamino)phenyl]methanone Chemical compound C1=CC(N(C)C)=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 XTQLJIHMIOXTMS-UHFFFAOYSA-N 0.000 claims description 2
- GSIMEYHPNMLREA-UHFFFAOYSA-N [4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)N2CCN(CCC=3C=CC(F)=CC=3)CC2)=C1 GSIMEYHPNMLREA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 2
- AOYABYIIPZVRPC-UHFFFAOYSA-N n-[4-[4-[2-(4-chlorophenyl)ethyl]piperazine-1-carbonyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 AOYABYIIPZVRPC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 229960005141 piperazine Drugs 0.000 claims 8
- MXRGJBQXGSTMQL-UHFFFAOYSA-N (2-chlorophenyl)-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C(=O)C=2C(=CC=CC=2)Cl)CC1 MXRGJBQXGSTMQL-UHFFFAOYSA-N 0.000 claims 1
- MWWDHIIGTNYFIC-UHFFFAOYSA-N (3-chlorophenyl)-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C(=O)C=2C=C(Cl)C=CC=2)CC1 MWWDHIIGTNYFIC-UHFFFAOYSA-N 0.000 claims 1
- USFHSUPDJPHDCH-UHFFFAOYSA-N (4-chlorophenyl)-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 USFHSUPDJPHDCH-UHFFFAOYSA-N 0.000 claims 1
- GWKFJCLHSBNKRR-UHFFFAOYSA-N (4-chlorophenyl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 GWKFJCLHSBNKRR-UHFFFAOYSA-N 0.000 claims 1
- XAWLTTKNJJTQOP-UHFFFAOYSA-N (4-fluorophenyl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=CC(F)=CC=2)CC1 XAWLTTKNJJTQOP-UHFFFAOYSA-N 0.000 claims 1
- JBZZYVLHSABMRQ-UHFFFAOYSA-N [4-[2-(3-chlorophenyl)ethyl]piperazin-1-yl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)N2CCN(CCC=3C=C(Cl)C=CC=3)CC2)=C1 JBZZYVLHSABMRQ-UHFFFAOYSA-N 0.000 claims 1
- LVVOLXVLYBAVSN-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2,4-dichlorophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C(=O)C=2C(=CC(Cl)=CC=2)Cl)CC1 LVVOLXVLYBAVSN-UHFFFAOYSA-N 0.000 claims 1
- BPBPJJOOTVZZFA-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2,6-dichlorophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C(=O)C=2C(=CC=CC=2Cl)Cl)CC1 BPBPJJOOTVZZFA-UHFFFAOYSA-N 0.000 claims 1
- WMZAGDKSMHFPIX-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 WMZAGDKSMHFPIX-UHFFFAOYSA-N 0.000 claims 1
- ZYAAYACQKSMOSR-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2,6-dimethylphenyl)methanone Chemical compound CC1=CC=CC(C)=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 ZYAAYACQKSMOSR-UHFFFAOYSA-N 0.000 claims 1
- KQHKRRSQPGNZBU-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2-fluorophenyl)methanone Chemical compound FC1=CC=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 KQHKRRSQPGNZBU-UHFFFAOYSA-N 0.000 claims 1
- OGVVWKXFDLLJGT-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 OGVVWKXFDLLJGT-UHFFFAOYSA-N 0.000 claims 1
- FWKINTJJDACZMR-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(3,5-dichlorophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C(=O)C=2C=C(Cl)C=C(Cl)C=2)CC1 FWKINTJJDACZMR-UHFFFAOYSA-N 0.000 claims 1
- ORGYHESNXRTMRD-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(3-fluorophenyl)methanone Chemical compound FC1=CC=CC(C(=O)N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=C1 ORGYHESNXRTMRD-UHFFFAOYSA-N 0.000 claims 1
- KHUTULPFVBWZME-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCN(CCC=2C=CC(Cl)=CC=2)CC1 KHUTULPFVBWZME-UHFFFAOYSA-N 0.000 claims 1
- SZFKPJVKDMGYOG-UHFFFAOYSA-N [4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-[3-(dimethylamino)phenyl]methanone Chemical compound CN(C)C1=CC=CC(C(=O)N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=C1 SZFKPJVKDMGYOG-UHFFFAOYSA-N 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 238000002844 melting Methods 0.000 description 46
- 230000008018 melting Effects 0.000 description 46
- 239000000243 solution Substances 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 238000001704 evaporation Methods 0.000 description 33
- 230000008020 evaporation Effects 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000002253 acid Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 230000000875 corresponding effect Effects 0.000 description 24
- 239000007858 starting material Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000000354 decomposition reaction Methods 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- GMIRFHIMHXOTKR-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1CCN1CCNCC1 GMIRFHIMHXOTKR-UHFFFAOYSA-N 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 229940086542 triethylamine Drugs 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000825 pharmaceutical preparation Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 239000000155 melt Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 150000001718 carbodiimides Chemical class 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VIOBGCWEHLRBEP-UHFFFAOYSA-N 3,4-dimethoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1OC VIOBGCWEHLRBEP-UHFFFAOYSA-N 0.000 description 5
- RUQIUASLAXJZIE-UHFFFAOYSA-N 3-methoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1 RUQIUASLAXJZIE-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 150000004820 halides Chemical class 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- LODHVDKKTUZVDK-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]piperazine Chemical compound C1=CC(F)=CC=C1CCN1CCNCC1 LODHVDKKTUZVDK-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 239000001828 Gelatine Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- LKUAPSRIYZLAAO-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine Chemical compound C1CNCCN1CCC1=CC=CC=C1 LKUAPSRIYZLAAO-UHFFFAOYSA-N 0.000 description 3
- CLKQGHYYLMDFID-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)ethyl]piperazine Chemical compound ClC1=CC=CC(CCN2CCNCC2)=C1 CLKQGHYYLMDFID-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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- 235000013681 dietary sucrose Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- QUNALZGLMQIJHN-UHFFFAOYSA-N diethylphosphorylcyanamide Chemical compound CCP(=O)(CC)NC#N QUNALZGLMQIJHN-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- BDXCIWATLNUYFD-UHFFFAOYSA-N ethyl 4-[2-(3-chlorophenyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CCC1=CC=CC(Cl)=C1 BDXCIWATLNUYFD-UHFFFAOYSA-N 0.000 description 1
- GMPKAZMLKJDHJB-UHFFFAOYSA-N ethyl 4-[2-(4-fluorophenyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CCC1=CC=C(F)C=C1 GMPKAZMLKJDHJB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-O hydron;1,3-oxazole Chemical class C1=COC=[NH+]1 ZCQWOFVYLHDMMC-UHFFFAOYSA-O 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical group CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- AJUXDFHPVZQOGF-UHFFFAOYSA-N n,n-dimethyl-1-naphthylamine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1 AJUXDFHPVZQOGF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- QHCCDDQKNUYGNC-UHFFFAOYSA-N n-ethylbutan-1-amine Chemical group CCCCNCC QHCCDDQKNUYGNC-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- CPGRMGOILBSUQC-UHFFFAOYSA-N phosphoryl azide Chemical class [N-]=[N+]=NP(=O)(N=[N+]=[N-])N=[N+]=[N-] CPGRMGOILBSUQC-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 0.000 description 1
- NRZWQKGABZFFKE-UHFFFAOYSA-N trimethylsulfonium Chemical compound C[S+](C)C NRZWQKGABZFFKE-UHFFFAOYSA-N 0.000 description 1
- YRYSAWZMIRQUBO-UHFFFAOYSA-N trimethylsulfoxonium Chemical compound C[S+](C)(C)=O YRYSAWZMIRQUBO-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000537834A CA1281328C (fr) | 1987-05-25 | 1987-05-25 | Piperazines disubstituees |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000537834A CA1281328C (fr) | 1987-05-25 | 1987-05-25 | Piperazines disubstituees |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1281328C true CA1281328C (fr) | 1991-03-12 |
Family
ID=4135734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000537834A Expired - Lifetime CA1281328C (fr) | 1987-05-25 | 1987-05-25 | Piperazines disubstituees |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1281328C (fr) |
-
1987
- 1987-05-25 CA CA000537834A patent/CA1281328C/fr not_active Expired - Lifetime
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| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |