JP2001500142A - D4受容体選択性を有するピペラジン誘導体 - Google Patents
D4受容体選択性を有するピペラジン誘導体Info
- Publication number
- JP2001500142A JP2001500142A JP10513215A JP51321598A JP2001500142A JP 2001500142 A JP2001500142 A JP 2001500142A JP 10513215 A JP10513215 A JP 10513215A JP 51321598 A JP51321598 A JP 51321598A JP 2001500142 A JP2001500142 A JP 2001500142A
- Authority
- JP
- Japan
- Prior art keywords
- piperazine
- formula
- compound
- pyridyl
- group
- 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.)
- Ceased
Links
- 150000004885 piperazines Chemical class 0.000 title claims abstract description 9
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title claims description 7
- -1 and / or the CN Chemical group 0.000 claims description 67
- 150000001875 compounds Chemical class 0.000 claims description 64
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 229940127557 pharmaceutical product Drugs 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 238000003797 solvolysis reaction Methods 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
- 239000007788 liquid Substances 0.000 claims 2
- RRLCBKCJYXFQHA-UHFFFAOYSA-N 2-[4-[(3-thiophen-3-ylphenyl)methyl]piperazin-1-yl]pyrimidine Chemical compound C=1C=CC(C2=CSC=C2)=CC=1CN(CC1)CCN1C1=NC=CC=N1 RRLCBKCJYXFQHA-UHFFFAOYSA-N 0.000 claims 1
- CQTUBBGJACSDPZ-UHFFFAOYSA-N 2-[4-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]piperazin-1-yl]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CN2CCN(CC2)C=2N=CC=CN=2)=C1 CQTUBBGJACSDPZ-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 238000006073 displacement reaction Methods 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003446 ligand Substances 0.000 abstract description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 abstract description 3
- 206010028813 Nausea Diseases 0.000 abstract description 3
- 208000018737 Parkinson disease Diseases 0.000 abstract description 3
- 206010043118 Tardive Dyskinesia Diseases 0.000 abstract description 3
- 229960003638 dopamine Drugs 0.000 abstract description 3
- 230000008693 nausea Effects 0.000 abstract description 3
- 201000000980 schizophrenia Diseases 0.000 abstract description 3
- 208000019901 Anxiety disease Diseases 0.000 abstract description 2
- 230000036506 anxiety Effects 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 206010029897 Obsessive thoughts Diseases 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
- 229960005141 piperazine Drugs 0.000 description 27
- 239000000203 mixture Substances 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- LCXSXBYYVYTYDY-BTJKTKAUSA-N (z)-but-2-enedioic acid;piperazine Chemical compound C1CNCCN1.OC(=O)\C=C/C(O)=O LCXSXBYYVYTYDY-BTJKTKAUSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 6
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- IVTZRJKKXSKXKO-UHFFFAOYSA-N 1-(2-fluorophenyl)piperazine Chemical compound FC1=CC=CC=C1N1CCNCC1 IVTZRJKKXSKXKO-UHFFFAOYSA-N 0.000 description 4
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 4
- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 3
- 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 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 206010008118 cerebral infarction Diseases 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
- 239000012154 double-distilled water Substances 0.000 description 3
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 3
- 229960002195 perazine Drugs 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- AUYNWRLEXAPZAJ-UHFFFAOYSA-N piperazine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CNCCN1 AUYNWRLEXAPZAJ-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- DVNDAKTXKXFWFD-BTJKTKAUSA-N (z)-but-2-enedioic acid;2-[4-[(3-thiophen-3-ylphenyl)methyl]piperazin-1-yl]pyrimidine Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC(C2=CSC=C2)=CC=1CN(CC1)CCN1C1=NC=CC=N1 DVNDAKTXKXFWFD-BTJKTKAUSA-N 0.000 description 2
- SDEFNDIWLCWEGE-UHFFFAOYSA-N 1-[[4-(4-fluorophenyl)pyridin-2-yl]methyl]-4-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCN(CC=2N=CC=C(C=2)C=2C=CC(F)=CC=2)CC1 SDEFNDIWLCWEGE-UHFFFAOYSA-N 0.000 description 2
- MTCBMUQLMNMMRF-UHFFFAOYSA-N 1-methyl-3-[4-(trifluoromethyl)phenyl]benzene Chemical group CC1=CC=CC(C=2C=CC(=CC=2)C(F)(F)F)=C1 MTCBMUQLMNMMRF-UHFFFAOYSA-N 0.000 description 2
- NPDIDUXTRAITDE-UHFFFAOYSA-N 1-methyl-3-phenylbenzene Chemical group CC1=CC=CC(C=2C=CC=CC=2)=C1 NPDIDUXTRAITDE-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- LHPFIIMSJANKNO-UHFFFAOYSA-N 2-[4-[[3-[4-(trifluoromethyl)phenyl]phenyl]methyl]piperazin-1-yl]pyrimidine Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC(CN2CCN(CC2)C=2N=CC=CN=2)=C1 LHPFIIMSJANKNO-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
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- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
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- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
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- UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 1
- MRDGZSKYFPGAKP-UHFFFAOYSA-N para-methoxyphenylpiperazine Chemical compound C1=CC(OC)=CC=C1N1CCNCC1 MRDGZSKYFPGAKP-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- OTRCLINFKXQIBG-UHFFFAOYSA-N propylsulfonyl propane-1-sulfonate Chemical compound CCCS(=O)(=O)OS(=O)(=O)CCC OTRCLINFKXQIBG-UHFFFAOYSA-N 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 210000001609 raphe nuclei Anatomy 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 229950001675 spiperone Drugs 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 108010021724 tonin Proteins 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- 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
- C07D295/06—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 halogen atoms or nitro radicals
- C07D295/073—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 halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- 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
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- 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
- C07D295/14—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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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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- 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
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- 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
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式I [式中、R1は、ピリジルまたはフェニルであり、各々は非置換または、Phま たは2−チエニルまたは3−チエニルによって単置換されており、 R2は、Ph’またはHetであり、 PhおよびPh’は、それぞれ互いに独立してフェニルであり、両方の基が各々 の場合に非置換またはF、Cl、Br、I、OH、OA、A、CF3、NO2、C N、COA、CONH2、CONHA、CONA2または2−チエニルまたは3− チエニルによって単置換、二置換または三置換されていてもよく、 Hetは、5−10員環の飽和、部分不飽和または完全不飽和の単環性複素環式 基または二環性複素環式基であり、1個または2個のN原子および/または1個 または2個のO原子が存在してもよく、複素環式基がF、Cl、Br、I、OA 、CF3、AまたはNO2によって単置換または二置換されていてもよく、そして Aは、1個から6個のC原子を有するアルキルである]のピペラジン誘導体およ びそれらの生理学的に許容される塩。 2. 請求項1に記載の (a) 1−(2−ピリミジニル)−4−[3−(3−チエニル)ベンジル]ピ ペラジン; (b) 1−[5−(4−フルオロフェニル)ピリド−3−イルメチル]−4− (2−ピリミジル)ピペラジン; (c) 4−[4−(3−ビフェニルメチル)−1−ピペラジニル]ベンゾニト リル; (d) 1−(4−クロロフェニル)−4−[5−(4−フルオロフェニル)− 3−ピリジルメチル)ピペラジン; (e) 1−(3’−フルオロ−3−ビフェニルメチル)−4−(2−ピリミジ ニル)ピペラジン; (f) 2−[4−(5−(3−チエニル)−3−ピリジルメチル)−1−ピペ ラジニル)ピリミジン およびそれらの塩。 3. 請求項1に記載の式Iのピペラジン誘導体およびそれらの塩の製造方法で あって、 式II [式中、R2は上記の意味を有する]の化合物を式III R1−CH2−L III [式中、Lは、Cl、Br、I、OH、O−CO−A、O−CO−Ph、O−SO2 −Arであり、Arはフェニルまたはトリルを表わし、およびAはアルキル、 または反応性にエステル化されている他のOH基または容易に求核置換される脱 離基を表わし、および R1は上記の意味を有する]の化合物と反応させるか、または式IV H2N−R2 IV [式中、R2は上記の意味を有する]の化合物を式V [式中、X1およびX2は、同一または異なっていてよく、Cl、Br、I、OH または反応性の官能基修飾されたOH基であり、R1は上記の意味を有する]の 化合物と反応させるか、または式VI [式中、R2、X1およびX2は、既に与えられた意味を有する]の化合物を式V II R1−CH2−NH2 VII [式中、R1は上記の意味を有する]の化合物と反応させるか、 または、1又は2以上の水素原子の代りに1又は2以上の還元される基および/ または1又は2以上の付加的C−Cおよび/またはC−N結合を有すること以外 は式Iに対応する化合物を還元剤で処理するか、 または、1又は2以上の水素原子の代りに1又は2以上の加溶媒分解基を有する こと以外は式Iに対応する化合物を加溶媒分解剤で処理するか、 および/または所望により、基R1および/またはR2を例えばOA基を切断して OH基を形成させたり、および/またはCN、COOHまたはCOOA基を誘導 体にして他の基R1および/またはR2に変換し、および/または例えば1級また は2級N原子をアルキル化したり、および/または式Iの生成塩基または酸を酸 または塩基と処理することによってそれらの塩に変換することを特徴とする、前 記製造方法。 4. 式Iで示される化合物および/またはその生理学的に許容される塩のひと つが、少なくともひとつの固体、液体または半液体の賦形剤または補助剤と一緒 になって適切な医薬剤形にされることを特徴とする、医薬品の製造方法。 5. 一般式Iで示される少なくともひとつの化合物および/またはその生理学 的に許容される塩を含むことを特徴とする、医薬品。 6. 請求項1に記載の式Iで示される化合物またはそれらの生理学的に許容さ れる塩の、薬剤の製造のための使用。 7. 請求項1に記載の式Iで示される化合物またはそれらの生理学的に許容さ れる塩の、疾病と闘うための使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19637237.2 | 1996-09-13 | ||
DE19637237A DE19637237A1 (de) | 1996-09-13 | 1996-09-13 | Piperazin-Derivate |
PCT/EP1997/004789 WO1998011068A1 (de) | 1996-09-13 | 1997-09-03 | Piperazin-derivate mit einer selektivität für den d-4 rezeptor |
Publications (2)
Publication Number | Publication Date |
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JP2001500142A true JP2001500142A (ja) | 2001-01-09 |
JP2001500142A5 JP2001500142A5 (ja) | 2005-05-12 |
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ID=7805470
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP10513215A Ceased JP2001500142A (ja) | 1996-09-13 | 1997-09-03 | D4受容体選択性を有するピペラジン誘導体 |
Country Status (23)
Country | Link |
---|---|
US (1) | US6258813B1 (ja) |
EP (1) | EP0931067B1 (ja) |
JP (1) | JP2001500142A (ja) |
KR (1) | KR20000036085A (ja) |
CN (1) | CN1114594C (ja) |
AR (1) | AR009770A1 (ja) |
AT (1) | ATE219768T1 (ja) |
AU (1) | AU724374B2 (ja) |
BR (1) | BR9712037A (ja) |
CA (1) | CA2266050C (ja) |
CZ (1) | CZ292210B6 (ja) |
DE (2) | DE19637237A1 (ja) |
DK (1) | DK0931067T3 (ja) |
ES (1) | ES2178011T3 (ja) |
HU (1) | HUP9904521A3 (ja) |
NO (1) | NO312589B1 (ja) |
PL (1) | PL332081A1 (ja) |
PT (1) | PT931067E (ja) |
RU (1) | RU2180660C2 (ja) |
SK (1) | SK282708B6 (ja) |
UA (1) | UA57749C2 (ja) |
WO (1) | WO1998011068A1 (ja) |
ZA (1) | ZA978194B (ja) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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JPWO2003002536A1 (ja) * | 2001-06-29 | 2004-10-14 | 興和株式会社 | 非対称環状ジアミン化合物 |
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JP2005239578A (ja) * | 2004-02-24 | 2005-09-08 | Teikoku Hormone Mfg Co Ltd | 5−ht1a作動作用と5−ht3拮抗作用を併有する薬剤 |
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RU2505536C1 (ru) * | 2012-12-29 | 2014-01-27 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Ярославский государственный технический университет" | 4-(1-гидрокси-1-метил-2-морфолиноэтил)бензойная и 4-(1-гидрокси-2-морфолиноциклогексил)бензойная кислоты, их фармацевтически приемлемые соли, сложные эфиры, обладающие анксиолитической активностью, и способ их получения |
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US5731438A (en) * | 1996-08-01 | 1998-03-24 | Isis Pharmaceuticals, Inc. | N-(aminoalkyl)-and/or N-(amidoalkyl)-dinitrogen heterocycles |
-
1996
- 1996-09-13 DE DE19637237A patent/DE19637237A1/de not_active Withdrawn
-
1997
- 1997-03-09 UA UA99041976A patent/UA57749C2/uk unknown
- 1997-09-03 US US09/254,489 patent/US6258813B1/en not_active Expired - Fee Related
- 1997-09-03 WO PCT/EP1997/004789 patent/WO1998011068A1/de not_active Application Discontinuation
- 1997-09-03 KR KR1019997002097A patent/KR20000036085A/ko not_active Application Discontinuation
- 1997-09-03 SK SK303-99A patent/SK282708B6/sk unknown
- 1997-09-03 PT PT97944823T patent/PT931067E/pt unknown
- 1997-09-03 AT AT97944823T patent/ATE219768T1/de not_active IP Right Cessation
- 1997-09-03 CA CA002266050A patent/CA2266050C/en not_active Expired - Fee Related
- 1997-09-03 DE DE59707613T patent/DE59707613D1/de not_active Expired - Fee Related
- 1997-09-03 CZ CZ1999824A patent/CZ292210B6/cs not_active IP Right Cessation
- 1997-09-03 EP EP97944823A patent/EP0931067B1/de not_active Expired - Lifetime
- 1997-09-03 JP JP10513215A patent/JP2001500142A/ja not_active Ceased
- 1997-09-03 DK DK97944823T patent/DK0931067T3/da active
- 1997-09-03 CN CN97197883A patent/CN1114594C/zh not_active Expired - Fee Related
- 1997-09-03 HU HU9904521A patent/HUP9904521A3/hu unknown
- 1997-09-03 BR BR9712037A patent/BR9712037A/pt not_active IP Right Cessation
- 1997-09-03 ES ES97944823T patent/ES2178011T3/es not_active Expired - Lifetime
- 1997-09-03 AU AU46203/97A patent/AU724374B2/en not_active Ceased
- 1997-09-03 RU RU99106804/04A patent/RU2180660C2/ru not_active IP Right Cessation
- 1997-09-03 PL PL97332081A patent/PL332081A1/xx unknown
- 1997-09-11 ZA ZA978194A patent/ZA978194B/xx unknown
- 1997-09-12 AR ARP970104189A patent/AR009770A1/es not_active Application Discontinuation
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1999
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003518096A (ja) * | 1999-12-22 | 2003-06-03 | アー カールッスン リサーチ アーベー | ドーパミン神経伝達の新規のモジュレーター |
JPWO2003002536A1 (ja) * | 2001-06-29 | 2004-10-14 | 興和株式会社 | 非対称環状ジアミン化合物 |
JPWO2003002535A1 (ja) * | 2001-06-29 | 2004-10-14 | 興和株式会社 | 六員環式基を有する環状ジアミン化合物 |
JP2005239578A (ja) * | 2004-02-24 | 2005-09-08 | Teikoku Hormone Mfg Co Ltd | 5−ht1a作動作用と5−ht3拮抗作用を併有する薬剤 |
JP4596792B2 (ja) * | 2004-02-24 | 2010-12-15 | あすか製薬株式会社 | 5−ht1a作動作用と5−ht3拮抗作用を併有する薬剤 |
WO2008047839A1 (fr) * | 2006-10-19 | 2008-04-24 | Dainippon Sumitomo Pharma Co., Ltd. | Agoniste du récepteur de la 5-ht1a |
US9834480B2 (en) | 2012-04-27 | 2017-12-05 | Yoshino Gypsum Co., Ltd. | Gypsum-based embedding material composition for casting |
Also Published As
Publication number | Publication date |
---|---|
NO312589B1 (no) | 2002-06-03 |
HUP9904521A3 (en) | 2001-07-30 |
DE19637237A1 (de) | 1998-03-19 |
PT931067E (pt) | 2002-11-29 |
HUP9904521A2 (hu) | 2000-05-28 |
EP0931067A1 (de) | 1999-07-28 |
NO991236D0 (no) | 1999-03-12 |
CZ292210B6 (cs) | 2003-08-13 |
US6258813B1 (en) | 2001-07-10 |
ATE219768T1 (de) | 2002-07-15 |
AU4620397A (en) | 1998-04-02 |
RU2180660C2 (ru) | 2002-03-20 |
KR20000036085A (ko) | 2000-06-26 |
EP0931067B1 (de) | 2002-06-26 |
AU724374B2 (en) | 2000-09-21 |
NO991236L (no) | 1999-03-12 |
BR9712037A (pt) | 1999-08-24 |
AR009770A1 (es) | 2000-05-03 |
CA2266050C (en) | 2007-05-22 |
UA57749C2 (uk) | 2003-07-15 |
ES2178011T3 (es) | 2002-12-16 |
CN1114594C (zh) | 2003-07-16 |
ZA978194B (en) | 1999-03-03 |
DE59707613D1 (de) | 2002-08-01 |
PL332081A1 (en) | 1999-08-30 |
WO1998011068A1 (de) | 1998-03-19 |
CZ82499A3 (cs) | 1999-06-16 |
SK282708B6 (sk) | 2002-11-06 |
CA2266050A1 (en) | 1998-03-19 |
SK30399A3 (en) | 2000-05-16 |
DK0931067T3 (da) | 2002-09-30 |
CN1230180A (zh) | 1999-09-29 |
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