CA1153377A - Piperazine derivatives as circulation-enhancing substances - Google Patents
Piperazine derivatives as circulation-enhancing substancesInfo
- Publication number
- CA1153377A CA1153377A CA000358914A CA358914A CA1153377A CA 1153377 A CA1153377 A CA 1153377A CA 000358914 A CA000358914 A CA 000358914A CA 358914 A CA358914 A CA 358914A CA 1153377 A CA1153377 A CA 1153377A
- Authority
- CA
- Canada
- Prior art keywords
- piperazine
- trimethoxybenzyl
- acid addition
- addition salt
- chemical equivalent
- 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
Links
- 239000000126 substance Substances 0.000 title claims description 36
- 150000004885 piperazines Chemical class 0.000 title description 4
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 81
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- 239000002253 acid Substances 0.000 claims abstract description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 4
- -1 3,4,5-trimethoxybenzyl halide Chemical class 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 27
- 239000000460 chlorine Substances 0.000 claims description 24
- 239000007858 starting material Substances 0.000 claims description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- YUPUSBMJCFBHAP-UHFFFAOYSA-N (3,4,5-trimethoxyphenyl)methanamine Chemical compound COC1=CC(CN)=CC(OC)=C1OC YUPUSBMJCFBHAP-UHFFFAOYSA-N 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
- PZIBVWUXWNYTNL-UHFFFAOYSA-N 1-(3-methoxyphenyl)piperazine Chemical compound COC1=CC=CC(N2CCNCC2)=C1 PZIBVWUXWNYTNL-UHFFFAOYSA-N 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 claims description 4
- JDVUSTNITSGJOH-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)piperazine Chemical compound CC1=CC=CC(C)=C1N1CCNCC1 JDVUSTNITSGJOH-UHFFFAOYSA-N 0.000 claims description 3
- MWNCHGVMCXDYED-UHFFFAOYSA-N 1-(2-methylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C(=CC=CC=2)C)=C1 MWNCHGVMCXDYED-UHFFFAOYSA-N 0.000 claims description 3
- QSTMOHFZTDLSBZ-UHFFFAOYSA-N 1-(3,4,5-trimethoxyphenyl)piperazine Chemical compound COC1=C(OC)C(OC)=CC(N2CCNCC2)=C1 QSTMOHFZTDLSBZ-UHFFFAOYSA-N 0.000 claims description 3
- SFLNVAVCCYTHCQ-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)piperazine Chemical compound C1=C(C)C(C)=CC=C1N1CCNCC1 SFLNVAVCCYTHCQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- QNCWKECHSBDMPF-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)piperazine Chemical compound C1=C2OCOC2=CC=C1N1CCNCC1 QNCWKECHSBDMPF-UHFFFAOYSA-N 0.000 claims description 2
- PWZDJIUQHUGFRJ-UHFFFAOYSA-N 1-(2-chlorophenyl)piperazine Chemical compound ClC1=CC=CC=C1N1CCNCC1 PWZDJIUQHUGFRJ-UHFFFAOYSA-N 0.000 claims description 2
- FBQIUSDQWOLCNY-UHFFFAOYSA-N 1-(2-ethoxyphenyl)piperazine Chemical compound CCOC1=CC=CC=C1N1CCNCC1 FBQIUSDQWOLCNY-UHFFFAOYSA-N 0.000 claims description 2
- LMQFWBCKQMNEEH-UHFFFAOYSA-N 1-(2-ethylphenyl)piperazine Chemical compound CCC1=CC=CC=C1N1CCNCC1 LMQFWBCKQMNEEH-UHFFFAOYSA-N 0.000 claims description 2
- WICKLEOONJPMEQ-UHFFFAOYSA-N 1-(2-methylphenyl)piperazine Chemical compound CC1=CC=CC=C1N1CCNCC1 WICKLEOONJPMEQ-UHFFFAOYSA-N 0.000 claims description 2
- ONEYFZXGNFNRJH-UHFFFAOYSA-N 1-(4-methylphenyl)piperazine Chemical compound C1=CC(C)=CC=C1N1CCNCC1 ONEYFZXGNFNRJH-UHFFFAOYSA-N 0.000 claims description 2
- KBJABLNQZCSKGE-UHFFFAOYSA-N 1-[3,5-bis(trifluoromethyl)phenyl]piperazine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(N2CCNCC2)=C1 KBJABLNQZCSKGE-UHFFFAOYSA-N 0.000 claims description 2
- RHEJPBFFJBKULZ-UHFFFAOYSA-N 4-chloro-n,n-bis(2-chloroethyl)-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N(CCCl)CCCl)=CC=C1Cl RHEJPBFFJBKULZ-UHFFFAOYSA-N 0.000 claims description 2
- GPEOAEVZTOQXLG-UHFFFAOYSA-N 4-piperazin-1-ium-1-ylphenolate Chemical compound C1=CC(O)=CC=C1N1CCNCC1 GPEOAEVZTOQXLG-UHFFFAOYSA-N 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000003701 inert diluent Substances 0.000 claims description 2
- QBVZHQVYUCIGOW-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-2-fluoroaniline Chemical compound FC1=CC=CC=C1N(CCCl)CCCl QBVZHQVYUCIGOW-UHFFFAOYSA-N 0.000 claims description 2
- WHBKJPHTKQXBNJ-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-4-fluoroaniline Chemical compound FC1=CC=C(N(CCCl)CCCl)C=C1 WHBKJPHTKQXBNJ-UHFFFAOYSA-N 0.000 claims description 2
- MRDGZSKYFPGAKP-UHFFFAOYSA-N para-methoxyphenylpiperazine Chemical compound C1=CC(OC)=CC=C1N1CCNCC1 MRDGZSKYFPGAKP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 19
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- KFLFHVONDSPSIU-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=C3OCOC3=CC=2)=C1 KFLFHVONDSPSIU-UHFFFAOYSA-N 0.000 claims 2
- CISYQFSUJSWXAB-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C(=CC=CC=2C)C)=C1 CISYQFSUJSWXAB-UHFFFAOYSA-N 0.000 claims 2
- ZMONCZQGFUAONA-UHFFFAOYSA-N 1-(2-chlorophenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C(=CC=CC=2)Cl)=C1 ZMONCZQGFUAONA-UHFFFAOYSA-N 0.000 claims 2
- LMOGEOIHIWFDKE-UHFFFAOYSA-N 1-(2-ethoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group CCOC1=CC=CC=C1N1CCN(CC=2C=C(OC)C(OC)=C(OC)C=2)CC1 LMOGEOIHIWFDKE-UHFFFAOYSA-N 0.000 claims 2
- SNXHCCNLKOFXDF-UHFFFAOYSA-N 1-(2-fluorophenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C(=CC=CC=2)F)=C1 SNXHCCNLKOFXDF-UHFFFAOYSA-N 0.000 claims 2
- DGDNVIQSKYNCRL-UHFFFAOYSA-N 1-(2-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=CC=CC=C1N1CCN(CC=2C=C(OC)C(OC)=C(OC)C=2)CC1 DGDNVIQSKYNCRL-UHFFFAOYSA-N 0.000 claims 2
- JUUYTIVVUMRNBQ-UHFFFAOYSA-N 1-(2-nitrophenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C(=CC=CC=2)[N+]([O-])=O)=C1 JUUYTIVVUMRNBQ-UHFFFAOYSA-N 0.000 claims 2
- QJSNYJAHNZGQMM-UHFFFAOYSA-N 1-(3,4,5-trimethoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=C(OC)C(OC)=C(OC)C=2)=C1 QJSNYJAHNZGQMM-UHFFFAOYSA-N 0.000 claims 2
- XMWYBCMUYDZSMM-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=C(C)C(C)=CC=2)=C1 XMWYBCMUYDZSMM-UHFFFAOYSA-N 0.000 claims 2
- JNWYVRLAZGEFRB-UHFFFAOYSA-N 1-(3-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=CC=CC(N2CCN(CC=3C=C(OC)C(OC)=C(OC)C=3)CC2)=C1 JNWYVRLAZGEFRB-UHFFFAOYSA-N 0.000 claims 2
- KKCOGNFFBYOKMA-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=CC(F)=CC=2)=C1 KKCOGNFFBYOKMA-UHFFFAOYSA-N 0.000 claims 2
- KMLFOAXUFSBRHD-UHFFFAOYSA-N 1-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group C1=CC(OC)=CC=C1N1CCN(CC=2C=C(OC)C(OC)=C(OC)C=2)CC1 KMLFOAXUFSBRHD-UHFFFAOYSA-N 0.000 claims 2
- ZHZNLIYRWRDRMU-UHFFFAOYSA-N 1-(4-methylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=CC(C)=CC=2)=C1 ZHZNLIYRWRDRMU-UHFFFAOYSA-N 0.000 claims 2
- YULDHMXAPUAMJK-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=C(C(Cl)=CC=2)C(F)(F)F)=C1 YULDHMXAPUAMJK-UHFFFAOYSA-N 0.000 claims 2
- NIQFIUZYSBPAKU-UHFFFAOYSA-N 1-[dimethoxy-(2-methoxyphenyl)methyl]-4-phenylpiperazine Chemical class COC1=CC=CC=C1C(OC)(OC)N1CCN(C=2C=CC=CC=2)CC1 NIQFIUZYSBPAKU-UHFFFAOYSA-N 0.000 claims 2
- IVWQZGCNXYXVRN-UHFFFAOYSA-N 4-[4-[(3,4,5-trimethoxyphenyl)methyl]piperazin-1-yl]phenol Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=CC(O)=CC=2)=C1 IVWQZGCNXYXVRN-UHFFFAOYSA-N 0.000 claims 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims 2
- JOIWQEYNQUFQNE-UHFFFAOYSA-N 1-(2-ethylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group CCC1=CC=CC=C1N1CCN(CC=2C=C(OC)C(OC)=C(OC)C=2)CC1 JOIWQEYNQUFQNE-UHFFFAOYSA-N 0.000 claims 1
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 claims 1
- YJRCDSXLKPERNV-UHFFFAOYSA-N 1-(2-nitrophenyl)piperazine Chemical compound [O-][N+](=O)C1=CC=CC=C1N1CCNCC1 YJRCDSXLKPERNV-UHFFFAOYSA-N 0.000 claims 1
- IKWIHGDLBMWYDK-UHFFFAOYSA-N 1-(3-methylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical group COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=C(C)C=CC=2)=C1 IKWIHGDLBMWYDK-UHFFFAOYSA-N 0.000 claims 1
- JOGGQYQUYDFUHO-UHFFFAOYSA-N 1-[3,5-bis(trifluoromethyl)phenyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C1 JOGGQYQUYDFUHO-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000011261 inert gas Substances 0.000 claims 1
- 230000004087 circulation Effects 0.000 abstract description 10
- CEBVRFRXNVJRMH-UHFFFAOYSA-N 1-[dimethoxy-(2-methoxyphenyl)methyl]piperazine Chemical class COC1=CC=CC=C1C(OC)(OC)N1CCNCC1 CEBVRFRXNVJRMH-UHFFFAOYSA-N 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- 230000002708 enhancing effect Effects 0.000 abstract description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 2
- 238000004458 analytical method Methods 0.000 description 19
- XXRUQNNAKXZSOS-UHFFFAOYSA-N 5-(chloromethyl)-1,2,3-trimethoxybenzene Chemical compound COC1=CC(CCl)=CC(OC)=C1OC XXRUQNNAKXZSOS-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 11
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 description 10
- 229960000876 cinnarizine Drugs 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000002792 vascular Effects 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 6
- 229960005141 piperazine Drugs 0.000 description 6
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- 229910052731 fluorine Inorganic materials 0.000 description 5
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- 231100000403 acute toxicity Toxicity 0.000 description 3
- 230000007059 acute toxicity Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 235000013539 calcium stearate Nutrition 0.000 description 2
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- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
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- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
- 229940038472 dicalcium phosphate Drugs 0.000 description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000004821 distillation Methods 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
- 239000008187 granular material Substances 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZDUKNPPJJCLUBH-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine;hydrochloride Chemical compound Cl.COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C=2C(=CC=CC=2C)C)=C1 ZDUKNPPJJCLUBH-UHFFFAOYSA-N 0.000 description 1
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- GIYJEMINTXWWNJ-UHFFFAOYSA-N dimethoxy-(2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1C(N)(OC)OC GIYJEMINTXWWNJ-UHFFFAOYSA-N 0.000 description 1
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- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
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- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
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- 239000000932 sedative agent Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
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- 238000011287 therapeutic dose Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP2934488.5 | 1979-08-25 | ||
| DE2934488A DE2934488C2 (de) | 1979-08-25 | 1979-08-25 | N-(Trimethoxybenzyl)-N'-(einfachsubstituierte-phenyl)-piperazine, deren Salze, Verfahren zu deren Herstellung und Arzneimittel |
| DEP2934450.1 | 1979-08-25 | ||
| DE19792934450 DE2934450C2 (de) | 1979-08-25 | 1979-08-25 | N-(Trimethoxybenzyl)-piperazinderivate und deren Salze, Verfahren zu deren Herstellung und Arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1153377A true CA1153377A (en) | 1983-09-06 |
Family
ID=25780725
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000358914A Expired CA1153377A (en) | 1979-08-25 | 1980-08-25 | Piperazine derivatives as circulation-enhancing substances |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US4370329A (OSRAM) |
| AT (1) | AT375075B (OSRAM) |
| AU (1) | AU538005B2 (OSRAM) |
| CA (1) | CA1153377A (OSRAM) |
| CH (1) | CH643549A5 (OSRAM) |
| DK (1) | DK363280A (OSRAM) |
| ES (1) | ES8104264A1 (OSRAM) |
| FR (1) | FR2463768A1 (OSRAM) |
| GB (1) | GB2057441B (OSRAM) |
| GR (1) | GR69917B (OSRAM) |
| HU (1) | HU182180B (OSRAM) |
| IL (1) | IL60891A (OSRAM) |
| MX (1) | MX6163E (OSRAM) |
| NL (1) | NL8004783A (OSRAM) |
| PL (1) | PL125663B1 (OSRAM) |
| SE (1) | SE8005943L (OSRAM) |
| SG (1) | SG3385G (OSRAM) |
| YU (1) | YU211480A (OSRAM) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4713382A (en) * | 1985-05-30 | 1987-12-15 | Syntex (U.S.A.) Inc. | N-phenyl-4-phenyl-1-piperazinecarboxamidines and related compounds as antiarrhythmic agents |
| IL85700A0 (en) * | 1987-03-24 | 1988-08-31 | Takeda Chemical Industries Ltd | 1,4-disubstituted piperazine compounds,their production and use |
| DE3715763A1 (de) * | 1987-05-12 | 1988-11-24 | Hoechst Ag | Diarylalkyl-substituierte alkylamine, verfahren zu ihrer herstellung, ihre verwendung sowie sie enthaltende arzneimittel |
| US5346653A (en) * | 1991-02-18 | 1994-09-13 | Matsushita Electric Industrial Co., Ltd. | Non-linear optical material, method of manufacturing the same and optical wavelength converter |
| WO1997041108A1 (en) * | 1996-04-30 | 1997-11-06 | Warner-Lambert Company | Substituted piperazines and piperidines as central nervous system agents |
| HUP9601331A3 (en) * | 1996-05-17 | 2000-06-28 | Egyt Gyogyszervegyeszeti Gyar | Piperazine- and homopiperazine-derivatives, process for producing them and pharmaceutical compositions containing them |
| US5859246A (en) * | 1997-01-30 | 1999-01-12 | Neurogen Corporation | 1-phenyl-4-benzylpiperazines: dopamine receptor subtype specific ligands |
| MXPA03000174A (es) | 2000-07-06 | 2003-09-22 | Neurogen Corp | Ligandos de receptor de hormona concentradora de melanina. |
| EP1389189A2 (en) * | 2001-05-22 | 2004-02-18 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted 1-benzyl-4-aryl piperazine analogues |
| RU2260431C2 (ru) * | 2003-12-15 | 2005-09-20 | Закрытое акционерное общество "Фармацевтическое предприятие "Оболенское" | Лекарственная форма, обладающая антиангинальным действием, и способ ее изготовления |
| WO2005110989A1 (en) * | 2004-04-07 | 2005-11-24 | Neurogen Corporation | Substituted 1-heteroaryl-4-substituted piperazine and piperidine analogues |
| WO2005110982A2 (en) * | 2004-04-07 | 2005-11-24 | Neurogen Corporation | Substituted 1-benzyl-4-substituted piperazine analogues |
| TW200609219A (en) * | 2004-06-17 | 2006-03-16 | Neurogen Corp | Aryl-substituted piperazine derivatives |
| RU2281772C1 (ru) * | 2005-02-14 | 2006-08-20 | Закрытое акционерное общество "Фармацевтическое предприятие "Оболенское" | Лекарственная форма, обладающая антиангинальным действием, и способ ее изготовления |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB868353A (en) | 1959-12-01 | 1961-05-17 | Soc Ind Fab Antibiotiques Sifa | Phenyl piperazine derivatives for therapeutic use and processes for the production of such derivatives |
| FR1275308A (fr) * | 1960-11-30 | 1961-11-03 | Soc Ind Fab Antibiotiques Sifa | Nouveaux dérivés de la phényl pipérazine, et leur préparation |
| GB939822A (en) * | 1961-03-29 | 1963-10-16 | Soc Ind Fab Antibiotiques Sifa | Piperazine compounds |
| US4100285A (en) | 1976-04-09 | 1978-07-11 | Nippon Shinyaku Co., Ltd. | N-substituted trialkoxybenzyl piperazine derivatives |
-
1980
- 1980-08-18 CH CH622980A patent/CH643549A5/de not_active IP Right Cessation
- 1980-08-19 AT AT0423080A patent/AT375075B/de active
- 1980-08-21 IL IL60891A patent/IL60891A/xx unknown
- 1980-08-22 FR FR8018407A patent/FR2463768A1/fr active Granted
- 1980-08-22 HU HU802091A patent/HU182180B/hu unknown
- 1980-08-22 DK DK363280A patent/DK363280A/da not_active Application Discontinuation
- 1980-08-22 MX MX808987U patent/MX6163E/es unknown
- 1980-08-22 ES ES494426A patent/ES8104264A1/es not_active Expired
- 1980-08-22 US US06/181,189 patent/US4370329A/en not_active Expired - Lifetime
- 1980-08-22 GB GB8027405A patent/GB2057441B/en not_active Expired
- 1980-08-24 NL NL8004783A patent/NL8004783A/nl not_active Application Discontinuation
- 1980-08-25 CA CA000358914A patent/CA1153377A/en not_active Expired
- 1980-08-25 AU AU61719/80A patent/AU538005B2/en not_active Ceased
- 1980-08-25 GR GR62738A patent/GR69917B/el unknown
- 1980-08-25 PL PL1980226396A patent/PL125663B1/pl unknown
- 1980-08-25 YU YU02114/80A patent/YU211480A/xx unknown
- 1980-08-25 SE SE8005943A patent/SE8005943L/xx not_active Application Discontinuation
-
1981
- 1981-10-05 US US06/308,607 patent/US4370330A/en not_active Expired - Fee Related
-
1985
- 1985-01-11 SG SG33/85A patent/SG3385G/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU6171980A (en) | 1981-03-05 |
| PL125663B1 (en) | 1983-06-30 |
| HU182180B (en) | 1983-12-28 |
| GB2057441A (en) | 1981-04-01 |
| DK363280A (da) | 1981-02-26 |
| US4370329A (en) | 1983-01-25 |
| US4370330A (en) | 1983-01-25 |
| NL8004783A (nl) | 1981-02-27 |
| FR2463768B1 (OSRAM) | 1983-11-25 |
| CH643549A5 (de) | 1984-06-15 |
| ATA423080A (de) | 1983-11-15 |
| GB2057441B (en) | 1983-05-25 |
| SE8005943L (sv) | 1981-02-26 |
| SG3385G (en) | 1985-06-14 |
| YU211480A (en) | 1983-06-30 |
| AU538005B2 (en) | 1984-07-26 |
| AT375075B (de) | 1984-06-25 |
| PL226396A1 (OSRAM) | 1981-10-30 |
| ES494426A0 (es) | 1981-04-01 |
| IL60891A (en) | 1984-03-30 |
| MX6163E (es) | 1984-11-29 |
| ES8104264A1 (es) | 1981-04-01 |
| FR2463768A1 (fr) | 1981-02-27 |
| IL60891A0 (en) | 1980-10-26 |
| GR69917B (OSRAM) | 1982-07-21 |
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