CZ303639B6 - N-Oxid derivátu 4-fenylpyridinu, zpusob jeho prípravy a lécivo s jeho obsahem - Google Patents
N-Oxid derivátu 4-fenylpyridinu, zpusob jeho prípravy a lécivo s jeho obsahem Download PDFInfo
- Publication number
- CZ303639B6 CZ303639B6 CZ20030428A CZ2003428A CZ303639B6 CZ 303639 B6 CZ303639 B6 CZ 303639B6 CZ 20030428 A CZ20030428 A CZ 20030428A CZ 2003428 A CZ2003428 A CZ 2003428A CZ 303639 B6 CZ303639 B6 CZ 303639B6
- Authority
- CZ
- Czechia
- Prior art keywords
- methyl
- bis
- oxide
- oxymorpholin
- tolylnicotinamide
- Prior art date
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- 150000001204 N-oxides Chemical class 0.000 title claims abstract description 58
- 239000003814 drug Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims description 19
- 238000000034 method Methods 0.000 title claims description 13
- 150000005362 4-phenylpyridines Chemical class 0.000 title claims description 5
- 230000008569 process Effects 0.000 title claims description 4
- -1 4-phenyl pyridine derivative N-oxide Chemical class 0.000 claims abstract description 95
- 150000001875 compounds Chemical class 0.000 claims abstract description 53
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 239000002253 acid Substances 0.000 claims abstract description 28
- 239000000651 prodrug Substances 0.000 claims abstract description 24
- 229940002612 prodrug Drugs 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims abstract description 9
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims abstract description 9
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 8
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000001302 tertiary amino group Chemical group 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 5
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 11
- 229940047889 isobutyramide Drugs 0.000 claims description 11
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007800 oxidant agent Substances 0.000 claims description 5
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 claims description 4
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229960003966 nicotinamide Drugs 0.000 claims description 4
- 239000011570 nicotinamide Substances 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 239000005557 antagonist Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 150000004682 monohydrates Chemical class 0.000 claims description 3
- 102000005962 receptors Human genes 0.000 claims description 3
- 108020003175 receptors Proteins 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- IXHFNEAFAWRVCF-UHFFFAOYSA-N n,2-dimethylpropanamide Chemical compound CNC(=O)C(C)C IXHFNEAFAWRVCF-UHFFFAOYSA-N 0.000 claims description 2
- KVNIEWQWLOMTMV-UHFFFAOYSA-N n-[(2-chloro-5-methoxyphenyl)methyl]-n-methyl-4-(2-methylphenyl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound COC1=CC=C(Cl)C(CN(C)C(=O)C=2C(=CC(=NC=2)N2CCOCC2)C=2C(=CC=CC=2)C)=C1 KVNIEWQWLOMTMV-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 235000005152 nicotinamide Nutrition 0.000 claims 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 abstract description 3
- 229910052740 iodine Inorganic materials 0.000 abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000001819 mass spectrum Methods 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
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- 239000007858 starting material Substances 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 18
- 229940079593 drug Drugs 0.000 description 17
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
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- 235000011152 sodium sulphate Nutrition 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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- 239000005051 trimethylchlorosilane Substances 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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Classifications
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- 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
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero 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
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Medicinal Chemistry (AREA)
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- Veterinary Medicine (AREA)
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- Biomedical Technology (AREA)
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- Immunology (AREA)
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- Rheumatology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Otolaryngology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00115287 | 2000-07-14 |
Publications (1)
| Publication Number | Publication Date |
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| CZ303639B6 true CZ303639B6 (cs) | 2013-01-23 |
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Family Applications (1)
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| CZ20030428A CZ303639B6 (cs) | 2000-07-14 | 2001-07-09 | N-Oxid derivátu 4-fenylpyridinu, zpusob jeho prípravy a lécivo s jeho obsahem |
Country Status (38)
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1103545E (pt) * | 1999-11-29 | 2004-03-31 | Hoffmann La Roche | 2-(3,5-bis-trifluorometil-fenil)-n-metil-n-(6-morfolin-4-il-4-o-totil-piridin-3-il)-isobutiramida |
| PT1303490E (pt) * | 2000-07-14 | 2008-09-04 | Hoffmann La Roche | Óxidos de aminas como pró-fármacos de antagonistas dosreceptores nk1, de derivados de 4-fenil-piridina |
| TWI287003B (en) * | 2000-07-24 | 2007-09-21 | Hoffmann La Roche | 4-phenyl-pyridine derivatives |
| ATE323531T1 (de) * | 2001-04-23 | 2006-05-15 | Hoffmann La Roche | Verwendung von nk-1-rezeptorantagonisten gegen benigne prostatahyperplasie |
| SI1643998T1 (sl) * | 2003-07-03 | 2007-12-31 | Hoffmann La Roche | Dvojni nk1/nk3 antagonisti za zdravljenje shizofrenije |
| CN1984891B (zh) | 2004-07-06 | 2012-08-08 | 弗·哈夫曼-拉罗切有限公司 | 用作合成nk-1受体拮抗剂的中间体的甲酰胺吡啶衍生物的制备方法 |
| US20060030600A1 (en) * | 2004-08-06 | 2006-02-09 | Patrick Schnider | Dual NK1/NK3 receptor antagonists for the treatment of schizophrenia |
| JP2008531509A (ja) | 2005-02-25 | 2008-08-14 | エフ．ホフマン−ラ ロシュ アーゲー | 医薬品成分の改良された分散性を有する錠剤 |
| CA2602445C (en) * | 2005-03-23 | 2013-08-20 | F.Hoffmann-La Roche Ag | Metabolites for nk-i antagonists for emesis |
| JP2008280248A (ja) * | 2005-11-02 | 2008-11-20 | Eisai R & D Management Co Ltd | アルツハイマー型痴呆症治療薬塩酸ドネペジルのプロドラッグ |
| WO2008090114A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 2-methoxy-5- (5-trifluoromethyl-tetrazol-i-yl-benzyl) - (2s-phenyl-piperidin-3s-yl-) |
| GB0808747D0 (en) | 2008-05-14 | 2008-06-18 | Glaxo Wellcome Mfg Pte Ltd | Novel compounds |
| US8966414B2 (en) | 2009-05-29 | 2015-02-24 | Cypress Semiconductor Corporation | Implementing a circuit using an integrated circuit including parametric analog elements |
| US9858367B1 (en) * | 2009-08-31 | 2018-01-02 | Cypress Semiconductor Corporation | Integrated circuit including parametric analog elements |
| PT2722045T (pt) | 2009-11-18 | 2016-10-18 | Helsinn Healthcare Sa | Composições para o tratamento de náuseas e vómitos mediadas centralmente |
| EP2722045B1 (en) | 2009-11-18 | 2016-07-06 | Helsinn Healthcare SA | Compositions for treating centrally mediated nausea and vomiting |
| ES2579616T3 (es) | 2011-10-18 | 2016-08-12 | Helsinn Healthcare Sa | Combinaciones terapéuticas de netupitant y palonosetrón |
| US8426450B1 (en) | 2011-11-29 | 2013-04-23 | Helsinn Healthcare Sa | Substituted 4-phenyl pyridines having anti-emetic effect |
| HK1203412A1 (en) | 2011-12-28 | 2015-10-30 | Global Blood Therapeutics, Inc. | Substituted heteroaryl aldehyde compounds and methods for their use in increasing tissue oxygenation |
| ES2643403T3 (es) | 2011-12-28 | 2017-11-22 | Global Blood Therapeutics, Inc. | Compuestos de benzaldehído sustituidos y métodos para su uso en el aumento de la oxigenación tisular |
| CN105073728A (zh) | 2013-03-15 | 2015-11-18 | 全球血液疗法股份有限公司 | 化合物及其用于调节血红蛋白的用途 |
| MX379235B (es) * | 2013-03-15 | 2025-03-11 | Global Blood Therapeutics Inc | Compuestos y sus usos para modular la hemoglobina. |
| US9422279B2 (en) | 2013-03-15 | 2016-08-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9802900B2 (en) | 2013-03-15 | 2017-10-31 | Global Blood Therapeutics, Inc. | Bicyclic heteroaryl compounds and uses thereof for the modulation of hemoglobin |
| US8952171B2 (en) | 2013-03-15 | 2015-02-10 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9458139B2 (en) | 2013-03-15 | 2016-10-04 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US10100043B2 (en) | 2013-03-15 | 2018-10-16 | Global Blood Therapeutics, Inc. | Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation |
| US9604999B2 (en) | 2013-03-15 | 2017-03-28 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| WO2014150258A1 (en) | 2013-03-15 | 2014-09-25 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US10266551B2 (en) | 2013-03-15 | 2019-04-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| RU2673084C2 (ru) | 2013-11-08 | 2018-11-22 | Киссеи Фармасьютикал Ко., Лтд. | Производное карбоксиметилпиперидина |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| US10350098B2 (en) * | 2013-12-20 | 2019-07-16 | Volcano Corporation | Devices and methods for controlled endoluminal filter deployment |
| CN114181195A (zh) | 2014-02-07 | 2022-03-15 | 全球血液疗法股份有限公司 | 一种化合物的结晶多晶型物 |
| TWI649307B (zh) | 2014-05-07 | 2019-02-01 | 日商橘生藥品工業股份有限公司 | Cyclohexylpyridine derivative |
| CN106588899B (zh) * | 2015-10-15 | 2019-11-15 | 江苏恒瑞医药股份有限公司 | 吡啶基取代的6-氧杂螺[4.5]癸烷类衍生物、其制备方法及其在医药上的应用 |
| SG11201804647TA (en) | 2015-12-04 | 2018-06-28 | Global Blood Therapeutics Inc | Dosing regimens for 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde |
| TWI663160B (zh) | 2016-05-12 | 2019-06-21 | 全球血液治療公司 | 用於合成2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)-吡啶-3-基)甲氧基)苯甲醛之方法 |
| TW202332423A (zh) | 2016-10-12 | 2023-08-16 | 美商全球血液治療公司 | 包含2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)吡啶-3-基)甲氧基)-苯甲醛之片劑 |
| IL312486B2 (en) | 2017-04-10 | 2025-05-01 | Chase Therapeutics Corp | NK1 antagonist combination and method for treating synucleinopathies |
| CN121221782A (zh) | 2017-06-30 | 2025-12-30 | 傲拓神经科学公司 | 用于治疗抑郁的nk-1拮抗剂组合物和方法 |
| US11014884B2 (en) | 2018-10-01 | 2021-05-25 | Global Blood Therapeutics, Inc. | Modulators of hemoglobin |
| US12479816B2 (en) | 2019-02-08 | 2025-11-25 | University of Pittsburgh—of the Commonwealth System of Higher Education | 20-HETE formation inhibitors |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1035115A1 (en) * | 1999-02-24 | 2000-09-13 | F. Hoffmann-La Roche Ag | 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists |
| EP1103545A1 (en) * | 1999-11-29 | 2001-05-30 | F. Hoffmann-La Roche Ag | 2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56106286A (en) | 1980-01-28 | 1981-08-24 | Nippon Musical Instruments Mfg | Electronic musical instrument |
| EP0103545A3 (en) | 1982-09-13 | 1984-10-03 | Arc Technologies Systems, Ltd. | Electrode for arc furnaces |
| IL111960A (en) | 1993-12-17 | 1999-12-22 | Merck & Co Inc | Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them |
| CA2178219C (en) | 1993-12-29 | 2005-03-22 | Raymond Baker | Substituted morpholine derivatives and their use as therapeutic agents |
| IL112778A0 (en) | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
| DE19627431A1 (de) * | 1996-07-08 | 1998-01-15 | Bayer Ag | Heterocyclisch kondensierte Pyridine |
| AR008789A1 (es) * | 1996-07-31 | 2000-02-23 | Bayer Corp | Piridinas y bifenilos substituidos |
| US5972938A (en) | 1997-12-01 | 1999-10-26 | Merck & Co., Inc. | Method for treating or preventing psychoimmunological disorders |
| HRP20010603A2 (en) * | 1999-02-24 | 2002-08-31 | Hoffmann La Roche | Phenyl-and pyridinyl derivatives |
| SI1157005T1 (en) * | 1999-02-24 | 2005-02-28 | F. Hoffmann-La Roche Ag | 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists |
| PT1303490E (pt) * | 2000-07-14 | 2008-09-04 | Hoffmann La Roche | Óxidos de aminas como pró-fármacos de antagonistas dosreceptores nk1, de derivados de 4-fenil-piridina |
| US20030083345A1 (en) * | 2001-07-10 | 2003-05-01 | Torsten Hoffmann | Method of treatment and/or prevention of brain, spinal or nerve injury |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1035115A1 (en) * | 1999-02-24 | 2000-09-13 | F. Hoffmann-La Roche Ag | 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists |
| EP1103545A1 (en) * | 1999-11-29 | 2001-05-30 | F. Hoffmann-La Roche Ag | 2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide |
Non-Patent Citations (1)
| Title |
|---|
| Y. IKEURA ET AL: "Potent NK1 Receptor Antagonists: Synthesis and Antagonistic Activity of Various Heterocycles with an N-3,5-bis(trifluoromethyl)benzyl-N-methylcarbamoyl Substituent" CHEM. PHARM. BULL., vol. 45, no. 10, 1997, str. 1642-1652; abstarkt * |
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| Date | Code | Title | Description |
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| MK4A | Patent expired |
Effective date: 20210709 |