JP4685331B2 - 複素環置換カルボニル誘導体およびドーパミンd3受容体リガンドとしてのその使用 - Google Patents
複素環置換カルボニル誘導体およびドーパミンd3受容体リガンドとしてのその使用 Download PDFInfo
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- JP4685331B2 JP4685331B2 JP2002565962A JP2002565962A JP4685331B2 JP 4685331 B2 JP4685331 B2 JP 4685331B2 JP 2002565962 A JP2002565962 A JP 2002565962A JP 2002565962 A JP2002565962 A JP 2002565962A JP 4685331 B2 JP4685331 B2 JP 4685331B2
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- Prior art keywords
- alkyl
- hydrogen
- compound
- halogen
- formula
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- 239000003446 ligand Substances 0.000 title description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 title description 2
- 125000000623 heterocyclic group Chemical group 0.000 title description 2
- 102000004073 Dopamine D3 Receptors Human genes 0.000 title 1
- 108090000525 Dopamine D3 Receptors Proteins 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims description 213
- 150000001875 compounds Chemical class 0.000 claims description 209
- 239000001257 hydrogen Substances 0.000 claims description 203
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 147
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 117
- -1 C 1 -C 6 alkyl Chemical class 0.000 claims description 111
- 150000002431 hydrogen Chemical class 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 79
- 229910052736 halogen Inorganic materials 0.000 claims description 73
- 150000002367 halogens Chemical class 0.000 claims description 73
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 66
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 37
- 108020003175 receptors Proteins 0.000 claims description 35
- 102000005962 receptors Human genes 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 34
- 229960003638 dopamine Drugs 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 20
- KSMVBYPXNKCPAJ-LJGSYFOKSA-N C[C@H]1CC[C@H](N)CC1 Chemical compound C[C@H]1CC[C@H](N)CC1 KSMVBYPXNKCPAJ-LJGSYFOKSA-N 0.000 claims description 19
- KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
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- 125000001424 substituent group Chemical group 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 13
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- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 208000011117 substance-related disease Diseases 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- IKQCKANHUYSABG-ZKCHVHJHSA-N CC[C@H]1CC[C@H](N)CC1 Chemical compound CC[C@H]1CC[C@H](N)CC1 IKQCKANHUYSABG-ZKCHVHJHSA-N 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
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- 208000019022 Mood disease Diseases 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
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- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 206010028813 Nausea Diseases 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 229940127239 5 Hydroxytryptamine receptor antagonist Drugs 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000017164 Chronobiology disease Diseases 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 230000005856 abnormality Effects 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000008693 nausea Effects 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 230000008085 renal dysfunction Effects 0.000 claims description 4
- 201000006152 substance dependence Diseases 0.000 claims description 4
- PINAYRGSNKSMKY-UHFFFAOYSA-N 1-[2-[4-[6-(trifluoromethyl)-1-benzothiophen-3-yl]piperazin-1-yl]ethyl]cyclopropane-1-carboxylic acid Chemical compound C1CN(C=2C3=CC=C(C=C3SC=2)C(F)(F)F)CCN1CCC1(C(=O)O)CC1 PINAYRGSNKSMKY-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- PAJFQEVFZACRCK-RJOZEALSSA-N C1C[C@@H](CC)CC[C@@H]1NC(=O)[C@H]1[C@H](CN2CCN(CC2)C=2C3=CC=C(C=C3SC=2)C(F)(F)F)C1 Chemical compound C1C[C@@H](CC)CC[C@@H]1NC(=O)[C@H]1[C@H](CN2CCN(CC2)C=2C3=CC=C(C=C3SC=2)C(F)(F)F)C1 PAJFQEVFZACRCK-RJOZEALSSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
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- 238000005859 coupling reaction Methods 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
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- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 230000003340 mental effect Effects 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 210000002569 neuron Anatomy 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
- 238000012544 monitoring process Methods 0.000 claims 2
- 238000002591 computed tomography Methods 0.000 claims 1
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 claims 1
- 229960002195 perazine Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 331
- 239000000243 solution Substances 0.000 description 187
- 239000000203 mixture Substances 0.000 description 150
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
- 235000019439 ethyl acetate Nutrition 0.000 description 128
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 122
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
- 239000007787 solid Substances 0.000 description 109
- 239000000047 product Substances 0.000 description 105
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 100
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 93
- 238000006243 chemical reaction Methods 0.000 description 90
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 76
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
- 239000003921 oil Substances 0.000 description 52
- 235000019198 oils Nutrition 0.000 description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 50
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- 239000012267 brine Substances 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 46
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 40
- 238000012360 testing method Methods 0.000 description 38
- 239000012074 organic phase Substances 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 34
- 235000019341 magnesium sulphate Nutrition 0.000 description 34
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- 239000002904 solvent Substances 0.000 description 32
- 229940079593 drug Drugs 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 29
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 28
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 28
- 239000000284 extract Substances 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
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- 239000000706 filtrate Substances 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 20
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000872 buffer Substances 0.000 description 19
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
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- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 16
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- 239000011734 sodium Substances 0.000 description 16
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 16
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- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 15
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 13
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- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- 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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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
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| PCT/US2002/004713 WO2002066446A1 (en) | 2001-02-16 | 2002-02-15 | Heterocyclic substituted carbonyl derivatives and their use as dopamine d3 receptor ligands |
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| US7880001B2 (en) * | 2004-04-29 | 2011-02-01 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme |
| US8415354B2 (en) * | 2004-04-29 | 2013-04-09 | Abbott Laboratories | Methods of use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US20100222316A1 (en) * | 2004-04-29 | 2010-09-02 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| WO2006074244A2 (en) | 2005-01-05 | 2006-07-13 | Abbott Laboratories | Adamantyl derivatives as inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US8198331B2 (en) | 2005-01-05 | 2012-06-12 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US20090192198A1 (en) | 2005-01-05 | 2009-07-30 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| JP5049267B2 (ja) * | 2005-04-26 | 2012-10-17 | ハイプニオン・インコーポレイテッド | ベンズイソオキサゾールピペラジン化合物およびその使用方法 |
| BRPI0611370A2 (pt) * | 2005-05-23 | 2010-08-31 | Sagami Chem Res | derivados de pirazol-1-carboxilato, processos para a producão destes e processos para a producão de derivados de pirazol |
| JP4855485B2 (ja) * | 2006-02-17 | 2012-01-18 | エフ.ホフマン−ラ ロシュ アーゲー | 5ht2/d3モジュレーターとしてのベンゾイル−ピペリジン誘導体 |
| US7435833B2 (en) * | 2006-04-07 | 2008-10-14 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme |
| CA2666275A1 (en) * | 2006-10-13 | 2008-04-17 | Neuromed Pharmaceuticals Ltd. | Cyclopropyl-piperazine compounds as calcium channel blockers |
| JP5502733B2 (ja) * | 2007-07-26 | 2014-05-28 | エフ.ホフマン−ラ ロシュ アーゲー | 5−ht2a及びd3受容体の二重のモジュレーター |
| JP5736098B2 (ja) | 2007-08-21 | 2015-06-17 | アッヴィ・インコーポレイテッド | 中枢神経系障害を治療するための医薬組成物 |
| FR2953839A1 (fr) * | 2009-12-14 | 2011-06-17 | Sanofi Aventis | Nouveaux derives d'(heterocycle-piperidine condensee)-(piperazinyl)-1alcanone ou d'(heterocycle-pyrrolidine condensee)-(piperazinyl)-1alcanone et leur utilisation comme inhibiteurs de p75 |
| FR2953836B1 (fr) * | 2009-12-14 | 2012-03-16 | Sanofi Aventis | Nouveaux derives (heterocycle-tetrahydro-pyridine)-(piperazinyl)-1-alcanone et (heterocycle-dihydro-pyrrolidine)-(piperazinyl)-1-alcanone et leur utilisation comme inhibiteurs de p75 |
| US8877778B2 (en) * | 2010-12-15 | 2014-11-04 | Hoffmann-La Roche Inc. | Benzofurane compounds |
| EP2487159A1 (en) | 2011-02-11 | 2012-08-15 | MSD Oss B.V. | RorgammaT inhibitors |
| US8921397B2 (en) * | 2011-05-04 | 2014-12-30 | Hoffmann-La Roche Inc. | Benzofurane-piperidine compounds |
| WO2014026330A1 (en) * | 2012-08-15 | 2014-02-20 | Merck Sharp & Dohme Corp. | 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF |
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| ES2842592T3 (es) * | 2014-05-19 | 2021-07-14 | Boehringer Ingelheim Animal Health Usa Inc | Compuestos antihelmínticos |
| EP3256450B1 (en) | 2015-02-11 | 2020-12-02 | Merck Sharp & Dohme Corp. | Substituted pyrazole compounds as ror-gamma-t inhibitors and uses thereof |
| WO2017075178A1 (en) | 2015-10-27 | 2017-05-04 | Merck Sharp & Dohme Corp. | SUBSTITUTED BICYCLIC PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF |
| AU2016344118A1 (en) | 2015-10-27 | 2018-05-10 | Merck Sharp & Dohme Corp. | Heteroaryl substituted benzoic acids as rorgammat inhibitors and uses thereof |
| RU2018117503A (ru) | 2015-10-27 | 2019-11-28 | Мерк Шарп И Доум Корп. | ЗАМЕЩЕННЫЕ ИНДАЗОЛЬНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ RORγТ И ИХ ПРИМЕНЕНИЕ |
| CN115572218B (zh) * | 2022-08-29 | 2024-04-16 | 江阴勒森生物科技有限公司 | 一种2-溴-3-羟基苯甲醛及其相关化学发光底物中间体的制备方法 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0311059A (ja) * | 1989-04-22 | 1991-01-18 | John Wyeth & Bros Ltd | ピペラジン誘導体類 |
| JPH06199784A (ja) * | 1991-08-13 | 1994-07-19 | Adir | 新規なアリールエチアミン化合物、その製法、及びこれを含有する医薬組成物。 |
| JPH08199784A (ja) * | 1995-01-26 | 1996-08-06 | Ig Tech Res Inc | 役物下型材 |
| JPH09511215A (ja) * | 1993-10-28 | 1997-11-11 | ヘキスト・マリオン・ルセル・インコーポレイテツド | ヘテロアリールピペリジン、ピロリジンおよびピペラジンならびに抗精神病剤および鎮痛剤としてのその使用 |
| JPH10502658A (ja) * | 1994-07-15 | 1998-03-10 | ビーエーエスエフ アクチェンゲゼルシャフト | ドーパミン−d▲下3▼−配位子としての複素環式化合物の使用 |
| JPH10152470A (ja) * | 1996-09-25 | 1998-06-09 | Yoshitomi Pharmaceut Ind Ltd | ピペラジン化合物 |
| JPH11147872A (ja) * | 1997-08-18 | 1999-06-02 | F Hoffmann La Roche Ag | Ccr−3受容体アンタゴニスト |
| JP2003519225A (ja) * | 1999-12-30 | 2003-06-17 | ハー・ルンドベック・アクチエゼルスカベット | 4−フェニル−1−ピペラジニル、−ピペリジニル、および−テトラヒドロピリジル誘導体 |
| JP2004501912A (ja) * | 2000-06-29 | 2004-01-22 | ハー・ルンドベック・アクチエゼルスカベット | Cns障害の治療に有用なインドール誘導体 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US354411A (en) | 1886-12-14 | Castle | ||
| US5116970A (en) * | 1988-02-18 | 1992-05-26 | New James S | Psychotropic heterobicycloalkylpiperazine derivatives: 2. fused pyridazinones |
| US5364866A (en) | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
| US5708018A (en) * | 1993-08-06 | 1998-01-13 | Pharmacia & Upjohn Company | 2-aminoindans as selective dopamine D3 ligands |
| GB9821978D0 (en) | 1998-10-08 | 1998-12-02 | Smithkline Beecham Plc | Compounds |
| GB0117950D0 (en) * | 2001-02-16 | 2001-09-19 | Aventis Pharma Inc | Novel heterocyclic urea derivatives andd their use as dopamine D3 receptor ligands |
-
2001
- 2001-07-19 GB GBGB0117577.7A patent/GB0117577D0/en not_active Ceased
-
2002
- 2002-02-15 JP JP2002565962A patent/JP4685331B2/ja not_active Expired - Fee Related
- 2002-02-15 DE DE60229673T patent/DE60229673D1/de not_active Expired - Lifetime
- 2002-02-15 CO CO02013028A patent/CO5370677A1/es not_active Application Discontinuation
- 2002-02-18 PA PA20028540001A patent/PA8540001A1/es unknown
- 2002-02-18 UY UY27179A patent/UY27179A1/es unknown
-
2004
- 2004-04-06 US US10/819,037 patent/US7186724B2/en not_active Expired - Fee Related
-
2007
- 2007-03-05 US US11/714,047 patent/US7521445B2/en not_active Expired - Fee Related
-
2009
- 2009-04-17 US US12/425,731 patent/US7772252B2/en not_active Expired - Fee Related
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0311059A (ja) * | 1989-04-22 | 1991-01-18 | John Wyeth & Bros Ltd | ピペラジン誘導体類 |
| JPH06199784A (ja) * | 1991-08-13 | 1994-07-19 | Adir | 新規なアリールエチアミン化合物、その製法、及びこれを含有する医薬組成物。 |
| JPH09511215A (ja) * | 1993-10-28 | 1997-11-11 | ヘキスト・マリオン・ルセル・インコーポレイテツド | ヘテロアリールピペリジン、ピロリジンおよびピペラジンならびに抗精神病剤および鎮痛剤としてのその使用 |
| JPH10502658A (ja) * | 1994-07-15 | 1998-03-10 | ビーエーエスエフ アクチェンゲゼルシャフト | ドーパミン−d▲下3▼−配位子としての複素環式化合物の使用 |
| JPH08199784A (ja) * | 1995-01-26 | 1996-08-06 | Ig Tech Res Inc | 役物下型材 |
| JPH10152470A (ja) * | 1996-09-25 | 1998-06-09 | Yoshitomi Pharmaceut Ind Ltd | ピペラジン化合物 |
| JPH11147872A (ja) * | 1997-08-18 | 1999-06-02 | F Hoffmann La Roche Ag | Ccr−3受容体アンタゴニスト |
| JP2003519225A (ja) * | 1999-12-30 | 2003-06-17 | ハー・ルンドベック・アクチエゼルスカベット | 4−フェニル−1−ピペラジニル、−ピペリジニル、および−テトラヒドロピリジル誘導体 |
| JP2004501912A (ja) * | 2000-06-29 | 2004-01-22 | ハー・ルンドベック・アクチエゼルスカベット | Cns障害の治療に有用なインドール誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CO5370677A1 (es) | 2004-02-27 |
| GB0117577D0 (en) | 2001-09-12 |
| PA8540001A1 (es) | 2002-12-30 |
| DE60229673D1 (de) | 2008-12-11 |
| US20040220173A1 (en) | 2004-11-04 |
| US20090247509A1 (en) | 2009-10-01 |
| US7521445B2 (en) | 2009-04-21 |
| US7186724B2 (en) | 2007-03-06 |
| JP2004518740A (ja) | 2004-06-24 |
| US7772252B2 (en) | 2010-08-10 |
| UY27179A1 (es) | 2002-07-31 |
| US20070161641A1 (en) | 2007-07-12 |
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