NO328714B1 - Aryl- og heteroarylpiperaziner, farmasoytiske preparater som omfatter minst en slik forbindelse, samt anvendelser av slike forbindelser til fremstilling av farmasoytiske preparater - Google Patents
Aryl- og heteroarylpiperaziner, farmasoytiske preparater som omfatter minst en slik forbindelse, samt anvendelser av slike forbindelser til fremstilling av farmasoytiske preparater Download PDFInfo
- Publication number
- NO328714B1 NO328714B1 NO20043709A NO20043709A NO328714B1 NO 328714 B1 NO328714 B1 NO 328714B1 NO 20043709 A NO20043709 A NO 20043709A NO 20043709 A NO20043709 A NO 20043709A NO 328714 B1 NO328714 B1 NO 328714B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- compound
- cycloalkyl
- alkoxy
- halogen
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 167
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 38
- 125000003118 aryl group Chemical group 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title description 17
- -1 cyan Chemical group 0.000 claims description 89
- 239000000203 mixture Substances 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
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- 206010033307 Overweight Diseases 0.000 claims description 8
- 235000020824 obesity Nutrition 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
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- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- JYNZIOFUHBJABQ-UHFFFAOYSA-N allyl-{6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl-}-methyl-amin Chemical compound C=1OC2=CC(OCCCCCCN(C)CC=C)=CC=C2C=1C1=CC=C(Br)C=C1 JYNZIOFUHBJABQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 4
- 235000014632 disordered eating Nutrition 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 201000003631 narcolepsy Diseases 0.000 claims description 4
- 208000032841 Bulimia Diseases 0.000 claims description 3
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000012886 Vertigo Diseases 0.000 claims description 2
- 230000036626 alertness Effects 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims description 2
- 235000019789 appetite Nutrition 0.000 claims description 2
- 230000036528 appetite Effects 0.000 claims description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
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- 231100000889 vertigo Toxicity 0.000 claims description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
- 206010020710 Hyperphagia Diseases 0.000 claims 1
- 208000007107 Stomach Ulcer Diseases 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 60
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 47
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 102000004384 Histamine H3 receptors Human genes 0.000 description 29
- 108090000981 Histamine H3 receptors Proteins 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000000556 agonist Substances 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 150000003254 radicals Chemical class 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
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- 239000007787 solid Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000005557 antagonist Substances 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- PVMCQBPJKPMOKM-UHFFFAOYSA-N 1-cyclopentylpiperazine Chemical compound C1CCCC1N1CCNCC1 PVMCQBPJKPMOKM-UHFFFAOYSA-N 0.000 description 8
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- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 8
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 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 7
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Classifications
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- 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
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US39930402P | 2002-07-26 | 2002-07-26 | |
DKPA200201142 | 2002-07-26 | ||
PCT/DK2003/000071 WO2003066604A2 (fr) | 2002-02-05 | 2003-02-05 | Nouvelles aryl- et heteroarylpiperazines |
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NO328714B1 true NO328714B1 (no) | 2010-05-03 |
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EP (1) | EP1474401A2 (fr) |
JP (1) | JP4607458B2 (fr) |
CN (1) | CN1628109A (fr) |
AU (2) | AU2003203148A1 (fr) |
BR (1) | BR0307429A (fr) |
CA (1) | CA2474214A1 (fr) |
IL (1) | IL162859A0 (fr) |
MX (1) | MXPA04007612A (fr) |
NO (1) | NO328714B1 (fr) |
PL (1) | PL372390A1 (fr) |
WO (1) | WO2003066604A2 (fr) |
ZA (1) | ZA200405694B (fr) |
Families Citing this family (72)
Publication number | Priority date | Publication date | Assignee | Title |
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US7390813B1 (en) | 2001-12-21 | 2008-06-24 | Xenon Pharmaceuticals Inc. | Pyridylpiperazines and aminonicotinamides and their use as therapeutic agents |
GB0224084D0 (en) * | 2002-10-16 | 2002-11-27 | Glaxo Group Ltd | Novel compounds |
EP1556046A1 (fr) | 2002-10-23 | 2005-07-27 | Janssen Pharmaceutica N.V. | Phenylpiperidines et phenylpyrrolidines utilisees comme modulateurs du recepteur h3 de l'histamine |
AU2004259263B2 (en) | 2003-07-29 | 2010-12-16 | High Point Pharmaceuticals, Llc | Pyridazinyl- piperazines and their use as histamine H3 receptor ligands |
RU2006105716A (ru) * | 2003-07-30 | 2007-09-10 | Зинон Фармасьютиклз Инк. (Ca) | Производные пиридазина и их применение в качестве терапевтических средств |
US7754711B2 (en) * | 2003-07-30 | 2010-07-13 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives and their use as therapeutic agents |
BRPI0412352A (pt) | 2003-07-30 | 2006-09-05 | Xenon Pharmaceuticals Inc | processo para a preparação de derivados de tetrazol de azidas de organo boro e organo alumìnio |
TWI345974B (en) | 2003-07-30 | 2011-08-01 | Xenon Pharmaceuticals Inc | Pyridazine derivatives and their use in the inhibition of stearoyl-coa desaturase |
WO2005035521A1 (fr) * | 2003-10-09 | 2005-04-21 | Argenta Discovery Ltd. | Quinoleines substituees, utilisees comme modulateurs de la mch |
GB0324159D0 (en) | 2003-10-15 | 2003-11-19 | Glaxo Group Ltd | Novel compounds |
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 |
CA2561791A1 (fr) * | 2004-03-31 | 2005-10-20 | Janssen Pharmaceutica, N.V. | Composes heterocycliques non-imidazole |
EP2305352A1 (fr) | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | Inhibiteurs de la 5-alpha-reductase pour le traitement d'hommes aux troubles métaboliques et anthropométriques |
US20050256309A1 (en) * | 2004-05-12 | 2005-11-17 | Altenbach Robert J | Tri-and bi-cyclic heteroaryl histamine-3 receptor ligands |
MXPA06015267A (es) * | 2004-06-22 | 2007-03-15 | Pfizer Prod Inc | Antagonistas diazabiciclicos del receptor histamina-3. |
CA2580857A1 (fr) * | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Derives heterocycliques et leur utilisation en tant qu'agents therapeutiques |
EP1807085B1 (fr) | 2004-09-20 | 2013-08-21 | Xenon Pharmaceuticals Inc. | Dérivés hétérocycliques et leur utilisation en tant qu'agents thérapeutiques |
CA2580781A1 (fr) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Derives heterocycliques bicycliques et leur utilisation comme inhibiteurs de stearoyl-coa desaturase (scd) |
US7919496B2 (en) | 2004-09-20 | 2011-04-05 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-CoA desaturase enzymes |
JP5043668B2 (ja) | 2004-09-20 | 2012-10-10 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 複素環誘導体および治療薬としてのそれらの使用 |
MX2007003330A (es) * | 2004-09-20 | 2007-06-05 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como agentes terapeuticos. |
JP5094398B2 (ja) | 2004-09-20 | 2012-12-12 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 複素環式誘導体およびステアロイル−CoAデサチュラーゼのメディエータとしてのそれらの使用 |
BRPI0515489A (pt) | 2004-09-20 | 2008-07-29 | Xenon Pharmaceuticals Inc | derivados heterocìclicos e sua utilização como inibidores de estearoil-coa desaturase |
CN101083992A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 抑制人硬脂酰CoA去饱和酶的哒嗪衍生物 |
ES2543813T3 (es) * | 2004-11-02 | 2015-08-24 | Northwestern University | Compuestos de piridazina para el tratamiento de enfermedades inflamatorias |
US7700595B2 (en) | 2005-03-01 | 2010-04-20 | Wyeth Llc | Cinnoline compounds |
WO2007130075A1 (fr) | 2005-06-03 | 2007-11-15 | Xenon Pharmaceuticals Inc. | Derives aminothiazole utilises en tant qu'inhibiteurs de la stearoyle-coa desaturase humaine |
ES2375929T3 (es) | 2005-07-04 | 2012-03-07 | High Point Pharmaceuticals, Llc | Antagonistas del receptor histamina h3. |
JP4787321B2 (ja) * | 2005-07-05 | 2011-10-05 | エフ.ホフマン−ラ ロシュ アーゲー | ピリダジン誘導体 |
US8686002B2 (en) | 2005-08-21 | 2014-04-01 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as binding partners for 5-HT5 receptors |
GB0517184D0 (en) * | 2005-08-22 | 2005-09-28 | Glaxo Group Ltd | Compounds |
ATE463481T1 (de) * | 2005-09-16 | 2010-04-15 | Janssen Pharmaceutica Nv | Cyclopropylamine als modulatoren des histamin-h3- rezeptors |
JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
CN101410385B (zh) | 2006-03-28 | 2011-08-24 | 高点制药有限责任公司 | 具有组胺h3受体活性的苯并噻唑类 |
CA2650625A1 (fr) * | 2006-04-28 | 2007-11-08 | Northwestern University | Formulations contenant un compose de pyridazine |
JP2009537596A (ja) | 2006-05-23 | 2009-10-29 | ハイ ポイント ファーマシューティカルズ,リミティド ライアビリティ カンパニー | 6−(4−シクロプロピルピペリジン−1−イル)−2’−メチル−[3,4’]−ビピリジン及びその医薬としての使用 |
SG163547A1 (en) | 2006-05-29 | 2010-08-30 | High Point Pharmaceuticals Llc | 3- (1, 3-benz0di0x0l-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine h3 receptor antagonist |
CN101495456B (zh) | 2006-05-30 | 2014-03-19 | 詹森药业有限公司 | 作为组胺h3受体的调节剂的取代的吡啶基酰胺化合物 |
CN101448820A (zh) * | 2006-05-30 | 2009-06-03 | 霍夫曼-拉罗奇有限公司 | 哌啶基嘧啶衍生物 |
WO2007150010A2 (fr) | 2006-06-23 | 2007-12-27 | Abbott Laboratories | Dérivés de cyclopropylamines |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
WO2008003702A2 (fr) * | 2006-07-03 | 2008-01-10 | Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg | Quinazolines et composés hétérocycliques associés, et leur utilisation dans le domaine thérapeutique |
JO2642B1 (en) | 2006-12-08 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
JO2849B1 (en) * | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
DK2148873T3 (da) | 2007-04-23 | 2012-11-26 | Janssen Pharmaceutica Nv | 4-alkoxypyridazinderivater som hurtigt dissocierende dopamin 2- receptorantagonister |
EP2148879B1 (fr) | 2007-04-23 | 2012-11-28 | Janssen Pharmaceutica, N.V. | Thia(dia)zoles en tant qu'antagonistes du récepteur de la dopamine à dissociation rapide |
JP5603770B2 (ja) * | 2007-05-31 | 2014-10-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr2受容体拮抗薬およびその使用 |
EP2014656A3 (fr) * | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | Nouveaux antagonistes d'hétéocycliques h3 |
KR20100039429A (ko) * | 2007-08-02 | 2010-04-15 | 에프. 호프만-라 로슈 아게 | Cns 질환의 치료를 위한 벤즈아미드 유도체의 용도 |
ES2384414T3 (es) | 2007-09-06 | 2012-07-04 | Glaxo Group Limited | Derivado de piperazina que tiene afinidad por el receptor H3 de histamina |
MY158253A (en) | 2007-11-20 | 2016-09-30 | Janssen Pharmaceutica Nv | Cycloalkyloxy- and heterocycloalkyloxypyridine compounds as modulators of the histamine h3 receptor |
WO2009079593A1 (fr) * | 2007-12-17 | 2009-06-25 | Janssen Pharmaceutica N.V. | Dérivés pipérazinyle utiles comme modulateurs du récepteur du neuropeptide y2 |
US20120129870A1 (en) * | 2007-12-17 | 2012-05-24 | Wenying Chai | Piperazinyl derivatives useful as modulators of the neuropeptide y2 receptor |
CN102159554B (zh) | 2008-07-03 | 2014-09-24 | 詹森药业有限公司 | 作为5-ht6受体拮抗剂的取代的6-(1-哌嗪基)-哒嗪 |
EA019048B1 (ru) | 2008-07-31 | 2013-12-30 | Янссен Фармацевтика Нв | Пиперазин-1-илтрифторметилзамещенные пиридины в качестве быстро диссоциирующихся антагонистов d-рецепторов дофамина |
PE20120061A1 (es) | 2008-12-19 | 2012-02-19 | Boehringer Ingelheim Int | Derivados de pirimidina como antagonistas del receptor ccr2 |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
BR112012015873B1 (pt) | 2009-12-17 | 2021-06-01 | Centrexion Therapeutics Corporation | Antagonistas de receptores ccr2 |
TWI510241B (zh) | 2010-02-18 | 2015-12-01 | Vtv Therapeutice Llc | 苯基-雜芳基衍生物及其使用方法 |
US8877745B2 (en) | 2010-05-12 | 2014-11-04 | Boehringer Ingelheim International Gmbh | CCR2 receptor antagonists, method for producing the same, and use thereof as medicaments |
WO2011141477A1 (fr) | 2010-05-12 | 2011-11-17 | Boehringer Ingelheim International Gmbh | Nouveaux antagonistes du récepteur ccr2, leur procédé de production et leur utilisation en tant que médicaments |
JP5647339B2 (ja) | 2010-05-17 | 2014-12-24 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr2アンタゴニスト及びこれらの使用 |
JP5636094B2 (ja) | 2010-05-25 | 2014-12-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ccr2受容体アンタゴニスト |
WO2011151251A1 (fr) | 2010-06-01 | 2011-12-08 | Boehringer Ingelheim International Gmbh | Nouveaux antagonistes du ccr2 |
US8853390B2 (en) | 2010-09-16 | 2014-10-07 | Abbvie Inc. | Processes for preparing 1,2-substituted cyclopropyl derivatives |
WO2013010839A1 (fr) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Antagonistes de ccr2 nouveaux et sélectifs |
WO2013151982A1 (fr) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Méthodes et composés utiles pour traiter le prurit, et procédés d'identification desdits composés |
BR112017002214B1 (pt) | 2014-08-04 | 2023-03-07 | Nuevolution A/S | Composto de fórmula (i), e uso de um composto |
BR112017028492B1 (pt) | 2015-07-02 | 2023-12-26 | Centrexion Therapeutics Corporation | Citrato de (4-((3r,4r)-3-metoxitetra-hidro-piran-4- ilamino)piperidin-1-il) (5- metil-6-(((2r, 6s)-6-(p-tolil) tetra-hidro-2h-piran-2-il)metilamino)pirimidin-4-il) metanona, seu uso e seu método de preparação, e composição farmacêutica |
AU2020405446A1 (en) | 2019-12-20 | 2022-05-26 | Nuevolution A/S | Compounds active towards nuclear receptors |
WO2021198956A1 (fr) | 2020-03-31 | 2021-10-07 | Nuevolution A/S | Composés actifs vis-à-vis des récepteurs nucléaires |
MX2022012260A (es) | 2020-03-31 | 2022-11-30 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB753166A (en) * | 1953-05-22 | 1956-07-18 | Miles Lab | Improvements in or relating to substituted piperazines |
US2993899A (en) * | 1958-03-31 | 1961-07-25 | Miles Lab | Acetylenically unsaturated piperazine derivatives |
US3309370A (en) * | 1964-07-16 | 1967-03-14 | Miles Lab | Bicycloalkyl piperazine derivatives and process |
FR2306694A1 (fr) * | 1975-04-07 | 1976-11-05 | Parcor | Derives de la piperazine |
US4144346A (en) * | 1977-01-31 | 1979-03-13 | Janssen Pharmaceutica N.V. | Novel 1-(1,3-dioxolan-2-ylmethyl)-1H-imidazoles |
US4163849A (en) * | 1978-03-17 | 1979-08-07 | Merck & Co., Inc. | Piperazinylpyrazines |
JPS56118074A (en) * | 1980-02-22 | 1981-09-16 | Tanabe Seiyaku Co Ltd | Propane derivative and its preparation |
US4339579A (en) * | 1980-12-29 | 1982-07-13 | American Home Products Corporation | 2,6-Bis-(pyrrolopyrazinyl)pyrazines |
US5001125A (en) * | 1984-03-26 | 1991-03-19 | Janssen Pharmaceutica N.V. | Anti-virally active pyridazinamines |
FR2573075B1 (fr) * | 1984-09-14 | 1987-03-20 | Innothera Lab Sa | Nouvelles (pyridyl-2)-1 piperazines, leur procede de preparation et leur application en therapeutique |
DK111387A (da) * | 1986-03-05 | 1987-09-06 | Otsuka Pharma Co Ltd | Carbostyrilderivater og salte deraf, laegemiddel indeholdende saadanne derivater samt fremgangsmaade til fremstilling af derivaterne |
JP2576862B2 (ja) * | 1986-03-05 | 1997-01-29 | 大塚製薬 株式会社 | カルボスチリル誘導体 |
AU639529B2 (en) * | 1987-03-04 | 1993-07-29 | Higuchi, Yoshinari | Carbostyril derivatives and salts thereof and anti-arrhythmic agents containing the carbostyril derivatives |
DE3803860A1 (de) * | 1988-02-09 | 1989-08-17 | Basf Ag | N,n'-disubstituierte piperazine |
US5021421A (en) * | 1989-03-03 | 1991-06-04 | Dainippon Pharmaceutical Co., Ltd. | 2-(1-Piperazinyl)-4-phenylcycloalkanopyridine derivatives, processes for the production thereof, and pharmaceutical composition containing the same |
GB9012316D0 (en) * | 1990-06-01 | 1990-07-18 | Wellcome Found | Pharmacologically active cns compounds |
WO1997002245A1 (fr) * | 1995-07-06 | 1997-01-23 | Japan Tobacco Inc. | Derives de benzamidoxime et leur utilisation a des fins medicinales |
JPH0971564A (ja) * | 1995-07-06 | 1997-03-18 | Japan Tobacco Inc | ベンズアミドオキシム誘導体及びその医薬用途 |
DZ2376A1 (fr) * | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant. |
EP1020445B1 (fr) * | 1997-10-02 | 2008-08-13 | Eisai R&D Management Co., Ltd. | Derives de pyridine condenses |
JP3989102B2 (ja) * | 1997-10-02 | 2007-10-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 縮合ピリジン誘導体 |
WO2000066578A1 (fr) * | 1999-04-30 | 2000-11-09 | Pfizer Products Inc. | Composes pour le traitement de l'obesite |
GB9926303D0 (en) * | 1999-11-05 | 2000-01-12 | Smithkline Beecham Plc | Novel compounds |
GB9926302D0 (en) * | 1999-11-05 | 2000-01-12 | Smithkline Beecham Plc | Novel compounds |
ES2243337T3 (es) * | 1999-12-16 | 2005-12-01 | Schering Corporation | Imidazoles sustituidos antagonistas del receptor y5 del neuropeptido y. |
FI20000480A0 (fi) * | 2000-03-01 | 2000-03-01 | Orion Yhtymae Oyj | Kinoliini- ja naftaleenijohdannaisia alfa-2 antagonisteina |
HUP0401858A3 (en) * | 2001-01-31 | 2009-06-29 | Lundbeck & Co As H | Gal3 receptor antagonist pyrimidine and indolone-derivatives and their use for preparation of pharmaceutical compositions suitable for the treatment of depression and/or anxiety |
AU2003229535A1 (en) * | 2002-06-06 | 2003-12-22 | Novo Nordisk A/S | Substituted hexahydropyrrolo(1,2-a)pyrazines, octahydropyrido(1,2-a)pyrazines and decahydropyrazino(1,2-a)azepines |
-
2003
- 2003-02-05 AU AU2003203148A patent/AU2003203148A1/en not_active Abandoned
- 2003-02-05 JP JP2003565978A patent/JP4607458B2/ja not_active Expired - Fee Related
- 2003-02-05 MX MXPA04007612A patent/MXPA04007612A/es not_active Application Discontinuation
- 2003-02-05 BR BR0307429-3A patent/BR0307429A/pt not_active Application Discontinuation
- 2003-02-05 CA CA002474214A patent/CA2474214A1/fr not_active Abandoned
- 2003-02-05 CN CNA038033607A patent/CN1628109A/zh active Pending
- 2003-02-05 IL IL16285903A patent/IL162859A0/xx unknown
- 2003-02-05 EP EP03701482A patent/EP1474401A2/fr not_active Withdrawn
- 2003-02-05 PL PL03372390A patent/PL372390A1/xx not_active Application Discontinuation
- 2003-02-05 WO PCT/DK2003/000071 patent/WO2003066604A2/fr active Application Filing
-
2004
- 2004-07-16 ZA ZA2004/05694A patent/ZA200405694B/en unknown
- 2004-09-03 NO NO20043709A patent/NO328714B1/no not_active IP Right Cessation
-
2010
- 2010-01-13 AU AU2010200135A patent/AU2010200135A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1474401A2 (fr) | 2004-11-10 |
AU2010200135A1 (en) | 2010-02-04 |
JP2005533747A (ja) | 2005-11-10 |
JP4607458B2 (ja) | 2011-01-05 |
MXPA04007612A (es) | 2004-11-10 |
WO2003066604A3 (fr) | 2003-12-04 |
AU2003203148A1 (en) | 2003-09-02 |
PL372390A1 (en) | 2005-07-25 |
NO20043709L (no) | 2004-09-03 |
BR0307429A (pt) | 2004-12-28 |
CA2474214A1 (fr) | 2003-08-14 |
CN1628109A (zh) | 2005-06-15 |
IL162859A0 (en) | 2005-11-20 |
WO2003066604A2 (fr) | 2003-08-14 |
ZA200405694B (en) | 2005-09-28 |
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