ZA200308638B - 4(Phenyl-piperazinyl-methyl)benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders. - Google Patents
4(Phenyl-piperazinyl-methyl)benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders. Download PDFInfo
- Publication number
- ZA200308638B ZA200308638B ZA200308638A ZA200308638A ZA200308638B ZA 200308638 B ZA200308638 B ZA 200308638B ZA 200308638 A ZA200308638 A ZA 200308638A ZA 200308638 A ZA200308638 A ZA 200308638A ZA 200308638 B ZA200308638 B ZA 200308638B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- formula
- methyl
- phenyl
- treatment
- Prior art date
Links
- 230000036407 pain Effects 0.000 title claims description 11
- 208000002193 Pain Diseases 0.000 title claims description 10
- 208000018522 Gastrointestinal disease Diseases 0.000 title claims description 8
- 208000019901 Anxiety disease Diseases 0.000 title claims description 5
- 230000036506 anxiety Effects 0.000 title claims description 5
- 150000003936 benzamides Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 77
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
- -1 4-benzyl-1-piperazinyl Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 230000004224 protection Effects 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 208000027520 Somatoform disease Diseases 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 208000027753 pain disease Diseases 0.000 claims description 3
- 229910015845 BBr3 Inorganic materials 0.000 claims description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 230000007017 scission Effects 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 8
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims 1
- AQJCXKVOPRUSOL-UHFFFAOYSA-N 4-[(3-aminophenyl)-(4-benzylpiperazin-1-yl)methyl]-n,n-diethylbenzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1C(C=1C=C(N)C=CC=1)N1CCN(CC=2C=CC=CC=2)CC1 AQJCXKVOPRUSOL-UHFFFAOYSA-N 0.000 claims 1
- NZXYDHJFJFWXKL-UHFFFAOYSA-N 4-[(3-aminophenyl)-[4-(thiophen-3-ylmethyl)piperazin-1-yl]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(N)C=CC=1)N1CCN(CC2=CSC=C2)CC1 NZXYDHJFJFWXKL-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- 208000014540 Functional gastrointestinal disease Diseases 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000001860 citric acid derivatives Chemical class 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940095064 tartrate Drugs 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 229910004373 HOAc Inorganic materials 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000000556 agonist Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 3
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 102000003840 Opioid Receptors Human genes 0.000 description 2
- 108090000137 Opioid Receptors Proteins 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000001949 anaesthesia Methods 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
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- 239000012074 organic phase Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical class OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- AZVSIHIBYRHSLB-UHFFFAOYSA-N 3-furaldehyde Chemical compound O=CC=1C=COC=1 AZVSIHIBYRHSLB-UHFFFAOYSA-N 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- HTLHMIALIFKABS-UHFFFAOYSA-N 4-[(3-aminophenyl)-(4-benzylpiperazin-1-yl)methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(N)C=CC=1)N1CCN(CC=2C=CC=CC=2)CC1 HTLHMIALIFKABS-UHFFFAOYSA-N 0.000 description 1
- MNUZJZQILRFDRM-UHFFFAOYSA-N 4-[(4-benzylpiperazin-1-yl)-(4-fluoro-3-hydroxyphenyl)methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C(F)=CC=1)N1CCN(CC=2C=CC=CC=2)CC1 MNUZJZQILRFDRM-UHFFFAOYSA-N 0.000 description 1
- DCZPTCGNXVKMTI-UHFFFAOYSA-N 4-[(4-fluoro-3-hydroxyphenyl)-[4-(thiophen-3-ylmethyl)piperazin-1-yl]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(O)C(F)=CC=1)N1CCN(CC2=CSC=C2)CC1 DCZPTCGNXVKMTI-UHFFFAOYSA-N 0.000 description 1
- KQWVAUSXZDRQPZ-UMTXDNHDSA-N 4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enyl-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide Chemical group C1=CC(C(=O)N(CC)CC)=CC=C1[C@H](C=1C=C(OC)C=CC=1)N1[C@@H](C)CN(CC=C)[C@H](C)C1 KQWVAUSXZDRQPZ-UMTXDNHDSA-N 0.000 description 1
- AKCMIUUHQWRJRW-UHFFFAOYSA-N 4-[[3-(methanesulfonamido)phenyl]-[4-(thiophen-3-ylmethyl)piperazin-1-yl]methyl]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1C(C=1C=C(NS(C)(=O)=O)C=CC=1)N1CCN(CC2=CSC=C2)CC1 AKCMIUUHQWRJRW-UHFFFAOYSA-N 0.000 description 1
- NALVGTOMKSKFFV-UHFFFAOYSA-N 4-fluoro-3-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1F NALVGTOMKSKFFV-UHFFFAOYSA-N 0.000 description 1
- YTDOXNTWNWFWPG-UHFFFAOYSA-N 4-iodo-n,n-di(propan-2-yl)benzamide Chemical compound CC(C)N(C(C)C)C(=O)C1=CC=C(I)C=C1 YTDOXNTWNWFWPG-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
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- 206010058019 Cancer Pain Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
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- 206010011224 Cough Diseases 0.000 description 1
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- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
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- 239000002253 acid Substances 0.000 description 1
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- 150000001448 anilines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
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- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
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- 229910052796 boron Inorganic materials 0.000 description 1
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- 230000005961 cardioprotection Effects 0.000 description 1
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- 238000003821 enantio-separation Methods 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 239000000842 neuromuscular blocking agent Substances 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0101772A SE0101772D0 (sv) | 2001-05-18 | 2001-05-18 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200308638B true ZA200308638B (en) | 2005-02-07 |
Family
ID=20284175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200308638A ZA200308638B (en) | 2001-05-18 | 2003-11-05 | 4(Phenyl-piperazinyl-methyl)benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders. |
Country Status (3)
| Country | Link |
|---|---|
| SE (1) | SE0101772D0 (sv) |
| UA (1) | UA77672C2 (sv) |
| ZA (1) | ZA200308638B (sv) |
-
2001
- 2001-05-18 SE SE0101772A patent/SE0101772D0/sv unknown
-
2002
- 2002-05-16 UA UA2003109695A patent/UA77672C2/uk unknown
-
2003
- 2003-11-05 ZA ZA200308638A patent/ZA200308638B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| UA77672C2 (en) | 2007-01-15 |
| SE0101772D0 (sv) | 2001-05-18 |
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