ZA200302452B - Derivatives of cyano-aryl (or cyanoheteroaryl)-carbonyl-piperazinyl-pyrimidines, their preparation and application as medication. - Google Patents
Derivatives of cyano-aryl (or cyanoheteroaryl)-carbonyl-piperazinyl-pyrimidines, their preparation and application as medication. Download PDFInfo
- Publication number
- ZA200302452B ZA200302452B ZA200302452A ZA200302452A ZA200302452B ZA 200302452 B ZA200302452 B ZA 200302452B ZA 200302452 A ZA200302452 A ZA 200302452A ZA 200302452 A ZA200302452 A ZA 200302452A ZA 200302452 B ZA200302452 B ZA 200302452B
- Authority
- ZA
- South Africa
- Prior art keywords
- cyano
- radical
- piperazinyl
- general formula
- pyridylcarbonyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 13
- 125000002944 cyanoaryl group Chemical group 0.000 title claims description 7
- 239000003814 drug Substances 0.000 title claims description 7
- 229940079593 drug Drugs 0.000 title description 4
- 239000002904 solvent Substances 0.000 claims description 39
- -1 1-imidazolyl group Chemical group 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 28
- 150000003254 radicals Chemical class 0.000 claims description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 150000001412 amines Chemical class 0.000 claims description 22
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- 230000003444 anaesthetic effect Effects 0.000 claims description 16
- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 150000001408 amides Chemical class 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 9
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- 230000018044 dehydration Effects 0.000 claims description 8
- 238000006297 dehydration reaction Methods 0.000 claims description 8
- 230000001624 sedative effect Effects 0.000 claims description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007825 activation reagent Substances 0.000 claims description 7
- 239000002249 anxiolytic agent Substances 0.000 claims description 7
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 7
- 239000011707 mineral Substances 0.000 claims description 7
- XRUBOKUVSYDOFW-UHFFFAOYSA-N 2-[4-(4-methoxypyrimidin-2-yl)piperazine-1-carbonyl]benzonitrile Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CC=2)C#N)=N1 XRUBOKUVSYDOFW-UHFFFAOYSA-N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 230000003387 muscular Effects 0.000 claims description 6
- 150000002923 oximes Chemical class 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 230000000147 hypnotic effect Effects 0.000 claims description 4
- 150000002500 ions Chemical class 0.000 claims description 4
- 239000000932 sedative agent Substances 0.000 claims description 4
- CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 150000005840 aryl radicals Chemical class 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- OSSIORZYXTUXBL-UHFFFAOYSA-N 2-methoxycarbonylpyridine-3-carboxylic acid Chemical compound COC(=O)C1=NC=CC=C1C(O)=O OSSIORZYXTUXBL-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 230000000202 analgesic effect Effects 0.000 claims description 2
- 230000000954 anitussive effect Effects 0.000 claims description 2
- 230000001430 anti-depressive effect Effects 0.000 claims description 2
- 230000002460 anti-migrenic effect Effects 0.000 claims description 2
- 230000000561 anti-psychotic effect Effects 0.000 claims description 2
- 229940124584 antitussives Drugs 0.000 claims description 2
- 230000000949 anxiolytic effect Effects 0.000 claims description 2
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 150000005698 chloropyrimidines Chemical class 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims description 2
- MCQOWYALZVKMAR-UHFFFAOYSA-N furo[3,4-b]pyridine-5,7-dione Chemical compound C1=CC=C2C(=O)OC(=O)C2=N1 MCQOWYALZVKMAR-UHFFFAOYSA-N 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 150000004885 piperazines Chemical class 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 229960002317 succinimide Drugs 0.000 claims description 2
- WOAQADGYFRJGCQ-UHFFFAOYSA-N 2-[4-(4-butoxypyrimidin-2-yl)piperazine-1-carbonyl]thiophene-3-carbonitrile Chemical compound CCCCOC1=CC=NC(N2CCN(CC2)C(=O)C2=C(C=CS2)C#N)=N1 WOAQADGYFRJGCQ-UHFFFAOYSA-N 0.000 claims 2
- QCSAYOGGAGBUPQ-UHFFFAOYSA-N 3-[4-(4-butoxypyrimidin-2-yl)piperazine-1-carbonyl]pyridine-4-carbonitrile Chemical compound CCCCOC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=NC=2)C#N)=N1 QCSAYOGGAGBUPQ-UHFFFAOYSA-N 0.000 claims 2
- RJKQHKGXWJMOJI-UHFFFAOYSA-N 4-[4-(4-butoxypyrimidin-2-yl)piperazine-1-carbonyl]pyridine-3-carbonitrile Chemical compound CCCCOC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CN=CC=2)C#N)=N1 RJKQHKGXWJMOJI-UHFFFAOYSA-N 0.000 claims 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 2
- IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 claims 2
- XZLGVTVWNZYREK-UHFFFAOYSA-N 4-[4-(4-butoxypyrimidin-2-yl)piperazine-1-carbonyl]pyridine-3-carbonitrile;hydrochloride Chemical compound Cl.CCCCOC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CN=CC=2)C#N)=N1 XZLGVTVWNZYREK-UHFFFAOYSA-N 0.000 claims 1
- FNJSWIPFHMKRAT-UHFFFAOYSA-N Monomethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(O)=O FNJSWIPFHMKRAT-UHFFFAOYSA-N 0.000 claims 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims 1
- 239000000935 antidepressant agent Substances 0.000 claims 1
- 229940005513 antidepressants Drugs 0.000 claims 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- ZQFYJHMUAWCEBH-UHFFFAOYSA-N furan-3-carbonitrile Chemical compound N#CC=1C=COC=1 ZQFYJHMUAWCEBH-UHFFFAOYSA-N 0.000 claims 1
- 150000007529 inorganic bases Chemical class 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 claims 1
- GSXCEVHRIVLFJV-UHFFFAOYSA-N thiophene-3-carbonitrile Chemical class N#CC=1C=CSC=1 GSXCEVHRIVLFJV-UHFFFAOYSA-N 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 50
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 238000009835 boiling Methods 0.000 description 13
- 239000003960 organic solvent Substances 0.000 description 13
- 238000010586 diagram Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 11
- 229960004134 propofol Drugs 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 150000008064 anhydrides Chemical class 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000011514 reflex Effects 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 206010002091 Anaesthesia Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 230000037005 anaesthesia Effects 0.000 description 5
- 238000001949 anaesthesia Methods 0.000 description 5
- 239000012964 benzotriazole Substances 0.000 description 5
- 150000001718 carbodiimides Chemical class 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000001632 sodium acetate Substances 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
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- 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
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- NTLRGKCNXOJGPY-UHFFFAOYSA-N 2-hydroxy-1,2$l^{5}-oxaphospholane 2-oxide Chemical compound OP1(=O)CCCO1 NTLRGKCNXOJGPY-UHFFFAOYSA-N 0.000 description 3
- KOSSOXUTKRWSAI-UHFFFAOYSA-N 4-ethoxy-2-piperazin-1-ylpyrimidine Chemical compound CCOC1=CC=NC(N2CCNCC2)=N1 KOSSOXUTKRWSAI-UHFFFAOYSA-N 0.000 description 3
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
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- YRLGFYYYQSKRDW-UHFFFAOYSA-N 2-[4-(4-ethoxypyrimidin-2-yl)piperazine-1-carbonyl]pyridine-3-carbonitrile Chemical compound CCOC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CN=2)C#N)=N1 YRLGFYYYQSKRDW-UHFFFAOYSA-N 0.000 description 2
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- PNQXFDWXVGOGAU-UHFFFAOYSA-N 2-[4-(4-ethoxypyrimidin-2-yl)piperazine-1-carbonyl]pyridine-3-carboxylic acid Chemical compound CCOC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CN=2)C(O)=O)=N1 PNQXFDWXVGOGAU-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200002532A ES2167276B1 (es) | 2000-10-20 | 2000-10-20 | Nuevos derivados de cianoaril (o cianoheteroaril)-carbonil-piperazinil-pirimidinas, su preparacion y su aplicacion como medicamentos. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200302452B true ZA200302452B (en) | 2004-03-29 |
Family
ID=8495344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200302452A ZA200302452B (en) | 2000-10-20 | 2003-03-28 | Derivatives of cyano-aryl (or cyanoheteroaryl)-carbonyl-piperazinyl-pyrimidines, their preparation and application as medication. |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US7300937B2 (xx) |
| EP (1) | EP1327630B1 (xx) |
| JP (1) | JP2004511550A (xx) |
| KR (1) | KR20030037687A (xx) |
| CN (1) | CN1221536C (xx) |
| AR (1) | AR030885A1 (xx) |
| AT (1) | ATE380795T1 (xx) |
| AU (2) | AU9387701A (xx) |
| BR (1) | BR0114999A (xx) |
| CA (1) | CA2426097A1 (xx) |
| CZ (1) | CZ20031116A3 (xx) |
| DE (1) | DE60131873T2 (xx) |
| ES (2) | ES2167276B1 (xx) |
| HK (1) | HK1060358A1 (xx) |
| HU (1) | HUP0302901A3 (xx) |
| IL (1) | IL155259A0 (xx) |
| MX (1) | MXPA03003348A (xx) |
| NO (1) | NO20031771L (xx) |
| NZ (1) | NZ525246A (xx) |
| PL (1) | PL361033A1 (xx) |
| PT (1) | PT1327630E (xx) |
| RU (1) | RU2259358C2 (xx) |
| TW (1) | TWI220144B (xx) |
| WO (1) | WO2002032880A1 (xx) |
| ZA (1) | ZA200302452B (xx) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL212089B1 (pl) * | 2002-03-13 | 2012-08-31 | Janssen Pharmaceutica Nv | Związki heterocykliczne jako inhibitory deacetylazy histonowej, kompozycja farmaceutyczna je zawierająca, ich zastosowanie, sposób wytwarzania, sposób wykrywania lub identyfikacji HDAC oraz kompozycja |
| CN103360343B (zh) * | 2012-03-30 | 2017-04-19 | 凯惠药业(上海)有限公司 | 一种哌嗪酰胺类化合物的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2535718A1 (fr) * | 1982-11-09 | 1984-05-11 | Sanofi Sa | (piperazinyl-1)-2 pyrimidines, leurs sels, procede pour leur preparation et compositions pharmaceutiques en contenant |
| US4547505A (en) * | 1983-03-25 | 1985-10-15 | Degussa Aktiengesellschaft | N-Phenyl-N-'-cycloalkylalkanoylpiperazine useful as analgetics and process for its production |
| US4668687A (en) * | 1984-07-23 | 1987-05-26 | Bristol-Myers Company | Psychogeriatric 1-(2-pyrimidinyl)piperazinyl derivatives of 1-pyrrolidin-2-ones |
| FR2642759B1 (fr) | 1989-02-09 | 1991-05-17 | Laboratorios Esteve Sa | Derives de pyrimidyl-piperazinyl-alkyl azoles avec activite anxiolytique et/ou tranquillisante |
| FR2654621B1 (fr) * | 1989-11-22 | 1994-09-23 | Esteve Labor Dr | Inhibition du syndrome d'abstinence. |
| FR2672052B1 (fr) * | 1991-01-28 | 1995-05-24 | Esteve Labor Dr | Derives d'aryl (ou heteroaryl)-piperazinyl-alkyl-azoles, leur preparation et leur application en tant que medicaments. |
| JPH04202185A (ja) * | 1990-11-30 | 1992-07-22 | Terumo Corp | ピペラジン誘導体及びこれを含有する医薬製剤 |
| ES2125206B1 (es) * | 1997-07-21 | 1999-11-16 | Esteve Labor Dr | Derivados de acil-piperazinil-pirimidinas, su preparacion y su aplicacion como medicamentos. |
-
2000
- 2000-10-20 ES ES200002532A patent/ES2167276B1/es not_active Expired - Fee Related
-
2001
- 2001-10-10 EP EP01974344A patent/EP1327630B1/en not_active Expired - Lifetime
- 2001-10-10 MX MXPA03003348A patent/MXPA03003348A/es active IP Right Grant
- 2001-10-10 CN CNB018176291A patent/CN1221536C/zh not_active Expired - Fee Related
- 2001-10-10 AT AT01974344T patent/ATE380795T1/de not_active IP Right Cessation
- 2001-10-10 NZ NZ525246A patent/NZ525246A/en unknown
- 2001-10-10 CZ CZ20031116A patent/CZ20031116A3/cs unknown
- 2001-10-10 US US10/312,195 patent/US7300937B2/en not_active Expired - Fee Related
- 2001-10-10 JP JP2002536263A patent/JP2004511550A/ja active Pending
- 2001-10-10 KR KR10-2003-7005303A patent/KR20030037687A/ko active IP Right Grant
- 2001-10-10 BR BR0114999-7A patent/BR0114999A/pt not_active IP Right Cessation
- 2001-10-10 PL PL01361033A patent/PL361033A1/xx not_active Application Discontinuation
- 2001-10-10 CA CA002426097A patent/CA2426097A1/en not_active Abandoned
- 2001-10-10 HU HU0302901A patent/HUP0302901A3/hu unknown
- 2001-10-10 AU AU9387701A patent/AU9387701A/xx active Pending
- 2001-10-10 RU RU2003114437/04A patent/RU2259358C2/ru not_active IP Right Cessation
- 2001-10-10 PT PT01974344T patent/PT1327630E/pt unknown
- 2001-10-10 ES ES01974344T patent/ES2296806T3/es not_active Expired - Lifetime
- 2001-10-10 AU AU2001293877A patent/AU2001293877B2/en not_active Ceased
- 2001-10-10 DE DE60131873T patent/DE60131873T2/de not_active Expired - Lifetime
- 2001-10-10 WO PCT/ES2001/000378 patent/WO2002032880A1/es active IP Right Grant
- 2001-10-10 IL IL15525901A patent/IL155259A0/xx unknown
- 2001-10-12 AR ARP010104819A patent/AR030885A1/es unknown
- 2001-10-17 TW TW090125627A patent/TWI220144B/zh not_active IP Right Cessation
-
2003
- 2003-03-28 ZA ZA200302452A patent/ZA200302452B/en unknown
- 2003-04-16 NO NO20031771A patent/NO20031771L/no not_active Application Discontinuation
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2004
- 2004-05-14 HK HK04103417A patent/HK1060358A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20031771L (no) | 2003-06-06 |
| AU9387701A (en) | 2002-04-29 |
| ES2167276B1 (es) | 2003-04-01 |
| HUP0302901A3 (en) | 2004-04-28 |
| RU2259358C2 (ru) | 2005-08-27 |
| EP1327630B1 (en) | 2007-12-12 |
| BR0114999A (pt) | 2004-02-03 |
| ATE380795T1 (de) | 2007-12-15 |
| DE60131873T2 (de) | 2008-12-04 |
| CA2426097A1 (en) | 2003-04-16 |
| IL155259A0 (en) | 2003-11-23 |
| NZ525246A (en) | 2004-11-26 |
| AR030885A1 (es) | 2003-09-03 |
| PL361033A1 (en) | 2004-09-20 |
| ES2296806T3 (es) | 2008-05-01 |
| CN1221536C (zh) | 2005-10-05 |
| HK1060358A1 (en) | 2004-08-06 |
| US7300937B2 (en) | 2007-11-27 |
| HUP0302901A2 (hu) | 2004-03-01 |
| NO20031771D0 (no) | 2003-04-16 |
| TWI220144B (en) | 2004-08-11 |
| EP1327630A1 (en) | 2003-07-16 |
| US20040048872A1 (en) | 2004-03-11 |
| KR20030037687A (ko) | 2003-05-14 |
| JP2004511550A (ja) | 2004-04-15 |
| WO2002032880A1 (es) | 2002-04-25 |
| CZ20031116A3 (cs) | 2003-10-15 |
| MXPA03003348A (es) | 2003-06-19 |
| CN1469866A (zh) | 2004-01-21 |
| ES2167276A1 (es) | 2002-05-01 |
| PT1327630E (pt) | 2008-03-05 |
| DE60131873D1 (de) | 2008-01-24 |
| AU2001293877B2 (en) | 2007-01-04 |
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