ES2260265T3 - Derivados de 4-fenilpiridina como antagonistas del receptor de la neuroquinina-1. - Google Patents
Derivados de 4-fenilpiridina como antagonistas del receptor de la neuroquinina-1.Info
- Publication number
- ES2260265T3 ES2260265T3 ES01960529T ES01960529T ES2260265T3 ES 2260265 T3 ES2260265 T3 ES 2260265T3 ES 01960529 T ES01960529 T ES 01960529T ES 01960529 T ES01960529 T ES 01960529T ES 2260265 T3 ES2260265 T3 ES 2260265T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- compound
- formula
- bis
- trifluoromethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000005557 antagonist Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 127
- -1 2-hydroxy-ethylamino Chemical group 0.000 claims abstract description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 41
- 239000002253 acid Substances 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000000460 chlorine Substances 0.000 claims abstract description 12
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 10
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims abstract description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims abstract description 3
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 23
- ADTNSTHKMIPKIJ-UHFFFAOYSA-N 1-[3,5-bis(trifluoromethyl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ADTNSTHKMIPKIJ-UHFFFAOYSA-N 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 10
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 9
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- 206010047700 Vomiting Diseases 0.000 claims description 7
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 7
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- 125000001424 substituent group Chemical group 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
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- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 6
- JGFYMRNGUGQDSG-UHFFFAOYSA-N n-[6-acetamido-4-(2-methylphenyl)pyridin-3-yl]-2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethylpropanamide Chemical compound C=1N=C(NC(C)=O)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JGFYMRNGUGQDSG-UHFFFAOYSA-N 0.000 claims description 6
- DYXGCFCUGZADFP-UHFFFAOYSA-N n-[6-amino-4-(2-methylphenyl)pyridin-3-yl]-2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DYXGCFCUGZADFP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- NIHBNLUMJKDSTD-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-(2-hydroxyethylamino)-4-(2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(NCCO)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NIHBNLUMJKDSTD-UHFFFAOYSA-N 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- IPDWLEJECDILKJ-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-(2,3-dihydro-1,4-oxazin-4-yl)-4-(2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2C=COCC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IPDWLEJECDILKJ-UHFFFAOYSA-N 0.000 claims description 4
- DDFMLVKZOKQQOD-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-imidazol-1-yl-4-(2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2C=NC=C2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DDFMLVKZOKQQOD-UHFFFAOYSA-N 0.000 claims description 4
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- FSDMACCWCGENQO-UHFFFAOYSA-N n-[6-[acetyl(methyl)amino]-4-(2-methylphenyl)pyridin-3-yl]-2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethylpropanamide Chemical compound C1=NC(N(C(C)=O)C)=CC(C=2C(=CC=CC=2)C)=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FSDMACCWCGENQO-UHFFFAOYSA-N 0.000 claims description 4
- GPPHCXLGQAMULD-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(1,2,4-triazol-1-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2N=CN=C2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GPPHCXLGQAMULD-UHFFFAOYSA-N 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- OERDCPDEJUGQEH-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[6-(methylamino)-4-(2-methylphenyl)pyridin-3-yl]propanamide Chemical compound CC(C)(C(N(C)C(C(C1=C(C)C=CC=C1)=C1)=CN=C1NC)=O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OERDCPDEJUGQEH-UHFFFAOYSA-N 0.000 claims description 3
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- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
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- 229960005181 morphine Drugs 0.000 claims description 3
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- UJIYLHIYNCDQKJ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-(2-hydroxyethylamino)-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(NCCO)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UJIYLHIYNCDQKJ-UHFFFAOYSA-N 0.000 claims description 3
- SNEGYVCKNWPDFO-HXUWFJFHSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2C[C@H](O)CC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SNEGYVCKNWPDFO-HXUWFJFHSA-N 0.000 claims description 3
- 230000008673 vomiting Effects 0.000 claims description 3
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical group C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
- 208000012545 Psychophysiologic disease Diseases 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
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- 208000030533 eye disease Diseases 0.000 claims 1
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical group NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 abstract 1
- BVNIREPGHLFKNZ-UHFFFAOYSA-N n-methylcyclopropanecarboxamide Chemical group CNC(=O)C1CC1 BVNIREPGHLFKNZ-UHFFFAOYSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 64
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- 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 description 8
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- 239000012279 sodium borohydride Substances 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
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- 239000002462 tachykinin receptor antagonist Substances 0.000 description 1
- 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 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- KPZSTOVTJYRDIO-UHFFFAOYSA-K trichlorocerium;heptahydrate Chemical compound O.O.O.O.O.O.O.Cl[Ce](Cl)Cl KPZSTOVTJYRDIO-UHFFFAOYSA-K 0.000 description 1
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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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- 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
Landscapes
- Organic Chemistry (AREA)
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- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
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- Addiction (AREA)
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- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00115846 | 2000-07-24 | ||
| EP00115846 | 2000-07-24 |
Publications (1)
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| ES2260265T3 true ES2260265T3 (es) | 2006-11-01 |
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| ES01960529T Expired - Lifetime ES2260265T3 (es) | 2000-07-24 | 2001-07-20 | Derivados de 4-fenilpiridina como antagonistas del receptor de la neuroquinina-1. |
Country Status (37)
Families Citing this family (23)
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| EP1103545B1 (en) * | 1999-11-29 | 2003-11-05 | 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 |
| DK1501808T3 (da) | 2002-04-26 | 2008-10-13 | Lilly Co Eli | Tachykininreceptor-antagonister |
| EA007720B1 (ru) | 2002-04-26 | 2006-12-29 | Эли Лилли Энд Компани | Производные триазола в качестве антагонистов рецептора тахикинина |
| AU2003300018A1 (en) * | 2002-10-11 | 2004-05-04 | Bristol-Myers Squibb Company | Process for the preparation of tri-nitrogen containing heteroaryl-diamine derivatives useful as pharmaceutical agents and methods of producing pharmaceutical agents |
| US20060160794A1 (en) * | 2003-06-12 | 2006-07-20 | Amegadzie Albert K | Tachykinin receptor antagonists |
| BRPI0412291A (pt) * | 2003-07-03 | 2006-09-19 | Hoffmann La Roche | antagonistas duplos de nka/nk3 para o tratamento de esquizofrenia |
| US7288658B2 (en) * | 2003-07-15 | 2007-10-30 | Hoffmann-La Roche Inc. | Process for preparation of pyridine derivatives |
| DE602005026669D1 (de) | 2004-07-06 | 2011-04-14 | Hoffmann La Roche | Herstellungsverfahren für carboxamid-pyridin-derivate als zwischenprodukte bei der synthese von nk-1-rezeptor-antagonisten |
| US20060030600A1 (en) * | 2004-08-06 | 2006-02-09 | Patrick Schnider | Dual NK1/NK3 receptor antagonists for the treatment of schizophrenia |
| US20060069086A1 (en) * | 2004-09-23 | 2006-03-30 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| US20080045610A1 (en) * | 2004-09-23 | 2008-02-21 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| 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 |
| US8067662B2 (en) | 2009-04-01 | 2011-11-29 | Aalnex, Inc. | Systems and methods for wound protection and exudate management |
| US7816577B2 (en) | 2006-02-13 | 2010-10-19 | Aalnex, Inc. | Wound shield |
| WO2007137954A1 (en) | 2006-05-31 | 2007-12-06 | F. Hoffmann-La Roche Ag | Aryl-4-ethynyl-isoxazole derivatives |
| EP2117538A1 (en) | 2007-01-24 | 2009-11-18 | 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 |
| US8426450B1 (en) | 2011-11-29 | 2013-04-23 | Helsinn Healthcare Sa | Substituted 4-phenyl pyridines having anti-emetic effect |
| PL3067349T3 (pl) | 2013-11-08 | 2018-06-29 | Kissei Pharmaceutical Co., Ltd. | Pochodna karboksymetylopiperydyny |
| TWI649307B (zh) | 2014-05-07 | 2019-02-01 | 日商橘生藥品工業股份有限公司 | Cyclohexylpyridine derivative |
| WO2016149324A1 (en) | 2015-03-16 | 2016-09-22 | Vanderbilt University | Negative allosteric modulators of metabotropic glutamate receptor 2 |
| CN115531553A (zh) * | 2015-12-22 | 2022-12-30 | 武田药品工业株式会社 | 内体g蛋白-偶联的受体的三部分调节剂 |
| ES2980110T3 (es) | 2018-02-26 | 2024-09-30 | Ospedale San Raffaele Srl | Antagonistas de NK-1 para uso en el tratamiento del dolor ocular |
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| IL111960A (en) | 1993-12-17 | 1999-12-22 | Merck & Co Inc | Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them |
| SK283070B6 (sk) | 1993-12-29 | 2003-02-04 | Merck Sharp & Dohme Limited | Substituované morfolínové deriváty, spôsob ich výroby, farmaceutický prostriedok s ich obsahom a ich použitie |
| IL112778A0 (en) | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
| US5972938A (en) | 1997-12-01 | 1999-10-26 | Merck & Co., Inc. | Method for treating or preventing psychoimmunological disorders |
| JPH11322748A (ja) * | 1998-03-19 | 1999-11-24 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| BR9908895A (pt) | 1998-03-19 | 2000-12-05 | Takeda Chemical Industries Ltd | Composição farmacêutica, composto, pró-medicamento, composições para antagonizar um receptor, uso de um composto, e, processos para produzir um composto, para antagonizar um receptor, para evitar ou tratar distúrbios de micção em mamìferos e distúrbios de asma, artrite reumatóide, osteoartrite, dor, tosse, sìndrome do intestino irritável ou vÈmitos em mamìferos |
| PL350428A1 (en) * | 1999-02-24 | 2002-12-16 | Hoffmann La Roche | 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists |
| 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 |
| PT1035115E (pt) * | 1999-02-24 | 2005-01-31 | Hoffmann La Roche | Derivados de 4-fenilpiridina e a sua utilizacao como antagonistas do receptor nk-1 |
| US6291465B1 (en) * | 1999-03-09 | 2001-09-18 | Hoffmann-La Roche Inc. | Biphenyl derivatives |
| EP1103545B1 (en) * | 1999-11-29 | 2003-11-05 | 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 |
| US6303790B1 (en) * | 1999-11-29 | 2001-10-16 | Hoffman-La Roche Inc. | Process for the preparation of pyridine derivatives |
| ATE400556T1 (de) * | 2000-07-14 | 2008-07-15 | Hoffmann La Roche | N-oxide als nk1-rezeptorantagonistenprodrugs von 4-phenylpyridinderivaten |
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- 2001-07-20 HU HU0301272A patent/HU229231B1/hu unknown
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