RU2201924C2 - Морфолиновое производное и фармацевтическая композиция на его основе - Google Patents
Морфолиновое производное и фармацевтическая композиция на его основе Download PDFInfo
- Publication number
- RU2201924C2 RU2201924C2 RU96115181/04A RU96115181A RU2201924C2 RU 2201924 C2 RU2201924 C2 RU 2201924C2 RU 96115181/04 A RU96115181/04 A RU 96115181/04A RU 96115181 A RU96115181 A RU 96115181A RU 2201924 C2 RU2201924 C2 RU 2201924C2
- Authority
- RU
- Russia
- Prior art keywords
- phenyl
- trifluoromethyl
- ethoxy
- morpholine
- methyl
- Prior art date
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- 150000002780 morpholines Chemical class 0.000 title claims abstract 3
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract 16
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 7
- 239000001257 hydrogen Substances 0.000 claims abstract 7
- 150000003839 salts Chemical class 0.000 claims abstract 6
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract 3
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract 3
- 125000001425 triazolyl group Chemical group 0.000 claims abstract 3
- 230000000694 effects Effects 0.000 claims abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 18
- -1 1- (S) - (3,5-bis (trifluoromethyl) phenyl) ethoxy Chemical group 0.000 claims 13
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 10
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical group 0.000 claims 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 229910052740 iodine Inorganic materials 0.000 claims 2
- 239000011630 iodine Substances 0.000 claims 2
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims 1
- JWXUKAGXMGNASM-VQTKTOELSA-N (2S,3S)-3-(4-fluorophenyl)-2-[(1R)-1-[3-fluoro-5-(trifluoromethyl)phenyl]ethoxy]morpholine Chemical compound FC=1C=C(C=C(C1)C(F)(F)F)[C@@H](C)O[C@H]1[C@@H](NCCO1)C1=CC=C(C=C1)F JWXUKAGXMGNASM-VQTKTOELSA-N 0.000 claims 1
- UTDANMPTVJPQFZ-OCBCSQNSSA-N (2r,3s)-2-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=CC=C1 UTDANMPTVJPQFZ-OCBCSQNSSA-N 0.000 claims 1
- AFBDSAJOMZYQAI-FJNPEDAXSA-N (2r,3s)-2-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=C(F)C=C1 AFBDSAJOMZYQAI-FJNPEDAXSA-N 0.000 claims 1
- UTDANMPTVJPQFZ-UYHISHBKSA-N (2r,3s)-2-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=CC=C1 UTDANMPTVJPQFZ-UYHISHBKSA-N 0.000 claims 1
- AFBDSAJOMZYQAI-CNOZUTPLSA-N (2s,3r)-2-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=C(F)C=C1 AFBDSAJOMZYQAI-CNOZUTPLSA-N 0.000 claims 1
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims 1
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims 1
- 102100024304 Protachykinin-1 Human genes 0.000 claims 1
- 101800003906 Substance P Proteins 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 4
- 125000005843 halogen group Chemical group 0.000 abstract 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- 102000007124 Tachykinin Receptors Human genes 0.000 abstract 1
- 108010072901 Tachykinin Receptors Proteins 0.000 abstract 1
- 239000005557 antagonist Substances 0.000 abstract 1
- 230000007721 medicinal effect Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
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- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16988993A | 1993-12-17 | 1993-12-17 | |
| US169,889 | 1993-12-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU96115181A RU96115181A (ru) | 1998-10-27 |
| RU2201924C2 true RU2201924C2 (ru) | 2003-04-10 |
Family
ID=22617632
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU96115181/04A RU2201924C2 (ru) | 1993-12-17 | 1994-12-13 | Морфолиновое производное и фармацевтическая композиция на его основе |
Country Status (40)
Families Citing this family (109)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69428913T2 (de) * | 1993-12-29 | 2002-05-29 | Merck Sharp & Dohme Ltd., Hoddesdon | Substituierte morpholinderivate und ihre verwendung als arzneimittel |
| TW385308B (en) * | 1994-03-04 | 2000-03-21 | Merck & Co Inc | Prodrugs of morpholine tachykinin receptor antagonists |
| JPH10500944A (ja) * | 1994-05-05 | 1998-01-27 | メルク シヤープ エンド ドーム リミテツド | モルホリン誘導体及びタキキニンのアンタゴニストとしてのそれらの使用 |
| WO1996005181A1 (en) * | 1994-08-15 | 1996-02-22 | Merck Sharp & Dohme Limited | Morpholine derivatives and their use as therapeutic agents |
| GB9417956D0 (en) * | 1994-09-02 | 1994-10-26 | Merck Sharp & Dohme | Therapeutic agents |
| GB9505491D0 (en) * | 1995-03-18 | 1995-05-03 | Merck Sharp & Dohme | Therapeutic agents |
| GB9511031D0 (en) * | 1995-06-01 | 1995-07-26 | Merck Sharp & Dohme | Chemical process |
| GB9513118D0 (en) * | 1995-06-28 | 1995-08-30 | Merck Sharp & Dohme | Therapeutic agents |
| GB9523244D0 (en) * | 1995-11-14 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
| US5750549A (en) * | 1996-10-15 | 1998-05-12 | Merck & Co., Inc. | Cycloalkyl tachykinin receptor antagonists |
| DE69838421D1 (en) * | 1997-07-02 | 2007-10-25 | Merck & Co Inc | Polymorphe form des tachykininrezeptorantagonisten 2-(r)-(1-(r)-(3,5-bis(trifluormethyl)phenyl)ethoxy)-3-(s)-(4-fluor)phenyl-4-(3-5-oxo-1h,4h-1,2,4-triazolo)methylmorpholin |
| ZA985765B (en) | 1997-07-02 | 1999-08-04 | Merck & Co Inc | Polymorphic form of a tachykinin receptor antagonist. |
| GB9813025D0 (en) * | 1998-06-16 | 1998-08-12 | Merck Sharp & Dohme | Chemical synthesis |
| CN1131212C (zh) * | 1999-02-24 | 2003-12-17 | 弗·哈夫曼-拉罗切有限公司 | 苯基－和吡啶基衍生物 |
| CN1134417C (zh) | 1999-02-24 | 2004-01-14 | 弗·哈夫曼-拉罗切有限公司 | 3-苯基吡啶衍生物及其作为nk-1受体拮抗剂的应用 |
| DE60045564D1 (de) | 1999-02-24 | 2011-03-03 | Hoffmann La Roche | 4-Phenylpyridinderivate und deren Verwendung als NK-1 Rezeptorantagonisten |
| US6291465B1 (en) | 1999-03-09 | 2001-09-18 | Hoffmann-La Roche Inc. | Biphenyl derivatives |
| US7163949B1 (en) | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
| KR100885986B1 (ko) | 1999-11-03 | 2009-03-03 | 에이엠알 테크놀로지, 인크. | 노르에피네프린, 도파민 및 세로토닌의 재흡수를 방지하기위한 아릴 및 헤테로아릴 치환된테트라하이드로이소퀴놀린 및 이들의 용도 |
| ES2208205T3 (es) * | 1999-11-29 | 2004-06-16 | F. Hoffmann-La Roche Ag | 2-(3,5-bis-trifluorometil-fenil)-n-metil-n-(6-morfolin-4-il-4-otolil-piridin-3-il)-isobutiramida. |
| US6452001B2 (en) | 2000-05-25 | 2002-09-17 | Hoffmann-La Roche Inc. | Diazapane derivatives useful as antagonists of neurokinin 1 receptor and methods for their formation |
| AR030284A1 (es) | 2000-06-08 | 2003-08-20 | Merck & Co Inc | Proceso para la sintesis de (2r, 2-alfa-r,3a) -2-[1-(3,5-bis(trifluorometil) fenil) etoxi]-3-(4-fluorofenil)-1,4-oxazina; dicho compuesto y sus formas polimorficas |
| US6482829B2 (en) | 2000-06-08 | 2002-11-19 | Hoffmann-La Roche Inc. | Substituted heterocyclic siprodecane compound active as an antagonist of neurokinin 1 receptor |
| CA2415532C (en) | 2000-07-11 | 2010-05-11 | Albany Molecular Research, Inc. | Novel 4-phenyl substituted tetrahydroisoquinolines therapeutic use thereof |
| CA2415890C (en) | 2000-07-14 | 2009-04-07 | F. Hoffmann-La Roche Ag | N-oxides as nk1 receptor antagonist prodrugs of 4-phenyl-pyridine derivatives |
| TWI287003B (en) | 2000-07-24 | 2007-09-21 | Hoffmann La Roche | 4-phenyl-pyridine derivatives |
| TWI259180B (en) | 2000-08-08 | 2006-08-01 | Hoffmann La Roche | 4-Phenyl-pyridine derivatives |
| YU39503A (sh) | 2000-11-22 | 2006-05-25 | F. Hoffmann-La Roche Ag. | Derivati pirimidina |
| US6642226B2 (en) | 2001-02-06 | 2003-11-04 | Hoffman-La Roche Inc. | Substituted phenyl-piperidine methanone compounds |
| DE60227657D1 (de) * | 2001-05-14 | 2008-08-28 | Hoffmann La Roche | 1-OXA-3,9-DIAZASPIROc5.5ÜUNDECAN-2-ONDERIVATE UND ZEPTORS |
| US6849624B2 (en) | 2001-07-31 | 2005-02-01 | Hoffmann-La Roche Inc. | Aromatic and heteroaromatic substituted amides |
| US6638981B2 (en) | 2001-08-17 | 2003-10-28 | Epicept Corporation | Topical compositions and methods for treating pain |
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