JP2012505165A5 - - Google Patents
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- Publication number
- JP2012505165A5 JP2012505165A5 JP2011530350A JP2011530350A JP2012505165A5 JP 2012505165 A5 JP2012505165 A5 JP 2012505165A5 JP 2011530350 A JP2011530350 A JP 2011530350A JP 2011530350 A JP2011530350 A JP 2011530350A JP 2012505165 A5 JP2012505165 A5 JP 2012505165A5
- Authority
- JP
- Japan
- Prior art keywords
- compound
- piperazinyl
- formula
- carboxamide
- pharmaceutically acceptable
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 85
- -1 aryl amide Chemical class 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 37
- 229940079593 drug Drugs 0.000 claims description 32
- 239000012453 solvate Substances 0.000 claims description 25
- 230000003287 optical effect Effects 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 208000011117 substance-related disease Diseases 0.000 claims description 21
- 206010013663 drug dependence Diseases 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 208000018737 Parkinson disease Diseases 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 11
- 201000000980 schizophrenia Diseases 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 9
- 101150065749 Churc1 gene Proteins 0.000 claims description 9
- 102100038239 Protein Churchill Human genes 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 9
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 9
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 108090000525 Dopamine D3 Receptors Proteins 0.000 claims description 8
- 230000036506 anxiety Effects 0.000 claims description 8
- 125000001769 aryl amino group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 208000019116 sleep disease Diseases 0.000 claims description 8
- 102000004073 Dopamine D3 Receptors Human genes 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 230000035882 stress Effects 0.000 claims description 7
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 6
- 206010057672 Male sexual dysfunction Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- KFYZFGITXAGRAU-SNAWJCMRSA-N n-[(e)-4-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-enyl]-2-oxo-3h-1,3-benzoxazole-5-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(C\C=C\CNC(=O)C=2C=C3NC(=O)OC3=CC=2)CC1 KFYZFGITXAGRAU-SNAWJCMRSA-N 0.000 claims description 6
- YVJJXJMWTLSCLC-UHFFFAOYSA-N n-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzothiazole-6-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCCNC(=O)C=2C=C3SC(=O)NC3=CC=2)CC1 YVJJXJMWTLSCLC-UHFFFAOYSA-N 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 150000001263 acyl chlorides Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- OUWBHSIWKJHFTM-SNAWJCMRSA-N n-[(e)-4-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-enyl]-2-oxo-3h-1,3-benzoxazole-6-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(C\C=C\CNC(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 OUWBHSIWKJHFTM-SNAWJCMRSA-N 0.000 claims description 5
- BITJJALJCISCRB-IHWYPQMZSA-N n-[(z)-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]but-2-enyl]-2-oxo-3h-1,3-benzoxazole-5-carboxamide Chemical compound CC1=CC=C(Cl)C=C1N1CCN(C\C=C/CNC(=O)C=2C=C3NC(=O)OC3=CC=2)CC1 BITJJALJCISCRB-IHWYPQMZSA-N 0.000 claims description 5
- BJCRWDBJVLWHSB-UHFFFAOYSA-N n-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzoxazole-6-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCCNC(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 BJCRWDBJVLWHSB-UHFFFAOYSA-N 0.000 claims description 5
- VIZDBZXBKIEXRK-UHFFFAOYSA-N n-[4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzoxazole-5-carboxamide Chemical compound CC1=CC=C(Cl)C=C1N1CCN(CCCCNC(=O)C=2C=C3NC(=O)OC3=CC=2)CC1 VIZDBZXBKIEXRK-UHFFFAOYSA-N 0.000 claims description 5
- JXLORNVFUOOEDW-UHFFFAOYSA-N n-[4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzoxazole-6-carboxamide Chemical compound CC1=CC=C(Cl)C=C1N1CCN(CCCCNC(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 JXLORNVFUOOEDW-UHFFFAOYSA-N 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 4
- 125000005116 aryl carbamoyl group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 230000003832 immune regulation Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- GFWSWYNCMRTUMO-UHFFFAOYSA-N n-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzothiazole-5-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCCNC(=O)C=2C=C3NC(=O)SC3=CC=2)CC1 GFWSWYNCMRTUMO-UHFFFAOYSA-N 0.000 claims description 4
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical group C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 claims description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical group C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- ASYHTIAJGDESLW-SNAWJCMRSA-N n-[(e)-4-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-enyl]-2-oxo-3h-1,3-benzothiazole-6-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(C\C=C\CNC(=O)C=2C=C3SC(=O)NC3=CC=2)CC1 ASYHTIAJGDESLW-SNAWJCMRSA-N 0.000 claims description 3
- WPJOIAJAKXXQBD-NSCUHMNNSA-N n-[(e)-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]but-2-enyl]-2-oxo-3h-1,3-benzoxazole-6-carboxamide Chemical compound CC1=CC=C(Cl)C=C1N1CCN(C\C=C\CNC(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 WPJOIAJAKXXQBD-NSCUHMNNSA-N 0.000 claims description 3
- YSJAMWLYJCEAQA-UHFFFAOYSA-N n-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzoxazole-5-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCCNC(=O)C=2C=C3NC(=O)OC3=CC=2)CC1 YSJAMWLYJCEAQA-UHFFFAOYSA-N 0.000 claims description 3
- FZLXHYUSNDHAFI-UHFFFAOYSA-N n-[4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzothiazole-5-carboxamide Chemical compound CC1=CC=C(Cl)C=C1N1CCN(CCCCNC(=O)C=2C=C3NC(=O)SC3=CC=2)CC1 FZLXHYUSNDHAFI-UHFFFAOYSA-N 0.000 claims description 3
- KAJSEQCXUPCWNB-UHFFFAOYSA-N n-[4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]butyl]-2-oxo-3h-1,3-benzothiazole-6-carboxamide Chemical compound CC1=CC=C(Cl)C=C1N1CCN(CCCCNC(=O)C=2C=C3SC(=O)NC3=CC=2)CC1 KAJSEQCXUPCWNB-UHFFFAOYSA-N 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims 2
- 235000002639 sodium chloride Nutrition 0.000 description 38
- 238000000034 method Methods 0.000 description 29
- 241001465754 Metazoa Species 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 238000012360 testing method Methods 0.000 description 21
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 229940125904 compound 1 Drugs 0.000 description 13
- 239000002552 dosage form Substances 0.000 description 13
- 239000003446 ligand Substances 0.000 description 13
- 229960005181 morphine Drugs 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 229960003878 haloperidol Drugs 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 9
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 9
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 8
- 101150049660 DRD2 gene Proteins 0.000 description 8
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- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 8
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- 239000000969 carrier Substances 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
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- 241000699666 Mus <mouse, genus> Species 0.000 description 6
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- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
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- 239000008103 glucose Substances 0.000 description 5
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- OBKXILSZNIKPPO-SNAWJCMRSA-N (e)-4-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-amine Chemical compound COC1=CC=CC=C1N1CCN(C\C=C\CN)CC1 OBKXILSZNIKPPO-SNAWJCMRSA-N 0.000 description 4
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
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- UFJPFLDFMPVGRW-UHFFFAOYSA-N 4-[4-(2-methoxyphenyl)piperazin-1-yl]butan-1-amine Chemical compound COC1=CC=CC=C1N1CCN(CCCCN)CC1 UFJPFLDFMPVGRW-UHFFFAOYSA-N 0.000 description 4
- OFEXISMCKCHYRA-UHFFFAOYSA-N 4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]butan-1-amine Chemical compound CC1=CC=C(Cl)C=C1N1CCN(CCCCN)CC1 OFEXISMCKCHYRA-UHFFFAOYSA-N 0.000 description 4
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- BXVHZIIFSRZVTC-UHFFFAOYSA-N 2-chloro-5-(2-methylphenyl)piperazine Chemical compound ClC1NCC(NC1)C1=C(C=CC=C1)C BXVHZIIFSRZVTC-UHFFFAOYSA-N 0.000 description 3
- QCYNXOWNRBRMFN-UHFFFAOYSA-N 2-oxo-3h-1,3-benzothiazole-6-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2NC(=O)SC2=C1 QCYNXOWNRBRMFN-UHFFFAOYSA-N 0.000 description 3
- USZSGINUZRHINQ-UHFFFAOYSA-N 2-oxo-3h-1,3-benzothiazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC(=O)SC2=C1 USZSGINUZRHINQ-UHFFFAOYSA-N 0.000 description 3
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
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| US9227944B2 (en) * | 2008-10-10 | 2016-01-05 | Institute Of Pharmacology And Toxicology Academy Of Military Science P.L.A. China | Dopamine D3 receptor ligands and preparation and medical uses of the same |
| CN103073524B (zh) * | 2013-01-25 | 2015-06-10 | 宁波市微循环与莨菪类药研究所 | 4-[4-(取代苯基)哌嗪基-1]-丁胺甲酸取代芳香酯衍生物及其制备方法 |
| CN105102448B (zh) | 2013-02-28 | 2018-03-06 | 百时美施贵宝公司 | 作为rock1和rock2抑制剂的苯基吡唑衍生物 |
| AR094929A1 (es) | 2013-02-28 | 2015-09-09 | Bristol Myers Squibb Co | Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2 |
| CN105461608B (zh) * | 2015-11-23 | 2017-11-28 | 东南大学 | 二氢吲哚‑2‑酮类d3受体配体及其制备方法和用途 |
| WO2018021447A1 (ja) | 2016-07-28 | 2018-02-01 | 塩野義製薬株式会社 | ドーパミンｄ３受容体拮抗作用を有する含窒素縮環化合物 |
| CN109419802B (zh) * | 2017-08-28 | 2023-01-13 | 中国人民解放军军事医学科学院毒物药物研究所 | 具有多巴胺d3受体调节活性的化合物及其用途 |
| CN108329282B (zh) * | 2018-01-16 | 2022-01-07 | 新乡医学院 | 一种苯基哌嗪类衍生物及其制备方法和应用 |
| US11447484B2 (en) | 2018-01-26 | 2022-09-20 | Shionogi & Co., Ltd. | Cyclic compound having dopamine D3 receptor antagonistic effect |
| CA3089498A1 (en) | 2018-01-26 | 2019-08-01 | Shionogi & Co., Ltd. | Condensed ring compounds having dopamine d3 receptor antagonistic effect |
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| FR2613365B1 (fr) | 1987-04-01 | 1989-07-28 | Adir | Nouveaux derives de l'amino tetrahydro-5, 6, 7, 8 naphto (2, 3b) furanne, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
| US5633377A (en) | 1990-12-28 | 1997-05-27 | Neurogen Corporation | 4-piperidino- and piperazinomethyl-2-cyclohexyl imidazole derivatives; dopamine receptor subtype specific ligands |
| JP3342491B2 (ja) | 1993-08-06 | 2002-11-11 | ファルマシア・アンド・アップジョン・カンパニー | 選択的ドーパミンｄ３リガンドとしての２−アミノインダン類 |
| US6756388B1 (en) | 1993-10-12 | 2004-06-29 | Pfizer Inc. | Benzothiophenes and related compounds as estrogen agonists |
| DE4425146A1 (de) | 1994-07-15 | 1996-01-18 | Basf Ag | Verwendung heterocyclischer Verbindungen |
| FR2742149B1 (fr) | 1995-12-11 | 1998-02-13 | Inst Nat Sante Rech Med | Nouveaux derives de 2-naphtamides et leurs applications therapeutiques |
| WO1997043262A1 (en) | 1996-05-11 | 1997-11-20 | Smithkline Beecham P.L.C. | Tetrahydroisoquinoline derivatives as modulators of dopamine d3 receptors |
| CA2263284A1 (en) | 1996-08-14 | 1998-02-19 | Smithkline Beecham P.L.C. | Tetrahydroisoquinoline derivatives and their pharmaceutical use |
| BR9809591A (pt) | 1997-05-03 | 2001-09-11 | Smithkline Beecham Plc | Derivados de tetraidoisoquinolina como moduladores de receptores de dopamina d3 |
| GB9821978D0 (en) | 1998-10-08 | 1998-12-02 | Smithkline Beecham Plc | Compounds |
| TWI274750B (en) | 1999-01-12 | 2007-03-01 | Abbott Gmbh & Co Kg | Triazole compounds showing high affinity to dopamine D3 receptor and pharmaceutical composition comprising the same |
| AU2002222315B2 (en) | 2000-11-30 | 2007-06-21 | Ranbaxy Laboratories Limited | 1,4-disubstituted piperazine derivatives useful as uro-selective alpha1-adrenoceptor blockers |
| KR100394083B1 (ko) | 2000-12-04 | 2003-08-06 | 학교법인 성신학원 | 도파민 ｄ3 및 ｄ4 수용체의 선택적 활성을 지닌 신규4,5-디히드로이소옥사졸릴알킬피페라진 유도체와, 이의제조방법 |
| HUP0103987A3 (en) | 2001-09-28 | 2004-11-29 | Richter Gedeon Vegyeszet | Phenylpiperazinylalkyl carboxylic acid amid derivatives, process for their preparation, pharmaceutical compositions containing them and their intermediates |
| GB0130219D0 (en) | 2001-12-18 | 2002-02-06 | Pfizer Ltd | Compounds for the treatment of sexual dysfunction |
| DE10232020A1 (de) | 2002-07-04 | 2004-02-26 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Neurorezeptoraktive Heteroarencarboxamide |
| KR20050075281A (ko) * | 2002-07-04 | 2005-07-20 | 쉬바르츠파르마에이지 | 씨엔에스 질병의 치료를 위한 도파민-디3 리간드로서헤테로아렌 카복스아미드의 용도 |
| US20040204422A1 (en) | 2003-04-14 | 2004-10-14 | Abbott Gmbh & Co. Kg. | N-[(Piperazinyl)hetaryl]arylsulfonamide compounds |
| ES2340941T3 (es) | 2004-08-09 | 2010-06-11 | ABBOTT GMBH & CO. KG | Compuestos de 4-piperazinil-pirimidina adecuados para tretar trastornos que responden a modulacion del receptor d 3 de dopamina. |
| JP2008521771A (ja) * | 2004-11-26 | 2008-06-26 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 改良された抗精神病活性および抗不安症活性を有するイソキサゾリン−インドール誘導体 |
| FR2878524B1 (fr) | 2004-12-01 | 2007-01-19 | Bioprojet Soc Civ Ile | Nouveaux derives d'arylpiperazine |
| DE102004063797A1 (de) | 2004-12-30 | 2006-07-13 | Schwarz Pharma Ag | Sauerstoffhaltige annelierte Phenylpiperazin- und Phenyldiazepancarboxamide |
| GB0517187D0 (en) | 2005-08-22 | 2005-09-28 | Glaxo Group Ltd | Compounds |
| JP2008115175A (ja) * | 2006-10-13 | 2008-05-22 | Otsuka Pharmaceut Co Ltd | 複素環化合物 |
| AR063302A1 (es) * | 2006-10-13 | 2009-01-21 | Otsuka Pharma Co Ltd | Derivados de 4-benzo[b]tiofen-4-il-piperazin-1-il con accion antagonista del receptor 5-ht2a de serotonina y receptor de adrenalina alfa1 y agonista parcial del receptor d2, una composicion farmaceutica que lo comprende y un proceso para producirla. |
| WO2009025265A1 (ja) * | 2007-08-21 | 2009-02-26 | Shionogi & Co., Ltd. | ピペラジン誘導体 |
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- 2009-09-28 EP EP09818738.8A patent/EP2354136B1/en active Active
- 2009-09-28 JP JP2011530350A patent/JP5701213B2/ja active Active
- 2009-09-28 WO PCT/CN2009/001096 patent/WO2010040274A1/zh not_active Ceased
- 2009-09-28 US US13/123,368 patent/US8829001B2/en active Active
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