HRP20010604A2 - 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists - Google Patents
3-phenylpyridine derivatives and their use as nk-1 receptor antagonists Download PDFInfo
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- HRP20010604A2 HRP20010604A2 HR20010604A HRP20010604A HRP20010604A2 HR P20010604 A2 HRP20010604 A2 HR P20010604A2 HR 20010604 A HR20010604 A HR 20010604A HR P20010604 A HRP20010604 A HR P20010604A HR P20010604 A2 HRP20010604 A2 HR P20010604A2
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- Croatia
- Prior art keywords
- methyl
- compound
- formula
- trifluoromethyl
- phenyl
- Prior art date
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- 108010040718 Neurokinin-1 Receptors Proteins 0.000 title claims description 8
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 title claims description 8
- 229940044551 receptor antagonist Drugs 0.000 title claims description 6
- 239000002464 receptor antagonist Substances 0.000 title claims description 6
- 150000005361 3-phenylpyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 116
- 238000000034 method Methods 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- -1 cyclic tertiary amine Chemical class 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229940047889 isobutyramide Drugs 0.000 claims description 4
- KICAKRBUXIXEIU-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-(2-chlorophenyl)-n-methyl-2-(4-methylpiperazin-1-yl)pyridine-4-carboxamide Chemical compound C=1C(N2CCN(C)CC2)=NC=C(C=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KICAKRBUXIXEIU-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- WRKCFWQULJFVBO-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[3-(2-methylphenyl)pyridin-4-yl]propanamide Chemical group C=1C=NC=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 WRKCFWQULJFVBO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- QOQSAUOBLCCCRM-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-5-(2-methoxyphenyl)-n-methyl-2-(4-methylpiperazin-1-yl)pyridine-4-carboxamide Chemical compound COC1=CC=CC=C1C1=CN=C(N2CCN(C)CC2)C=C1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 QOQSAUOBLCCCRM-UHFFFAOYSA-N 0.000 claims description 3
- HJBXFIIMRLNJEP-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-(2-methoxyphenyl)-n-methyl-2-(4-methylpiperazin-1-yl)pyridine-4-carboxamide Chemical compound COC1=CC=CC=C1C1=CN=C(N2CCN(C)CC2)C=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HJBXFIIMRLNJEP-UHFFFAOYSA-N 0.000 claims description 3
- KEIMCAPEIBJVLW-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-2-(4-methylpiperazin-1-yl)-5-phenylpyridine-4-carboxamide Chemical compound C=1C(N2CCN(C)CC2)=NC=C(C=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KEIMCAPEIBJVLW-UHFFFAOYSA-N 0.000 claims description 3
- SCPYZUAEPUWQKQ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-3-(2-methylphenyl)pyridine-4-carboxamide Chemical compound C=1C=NC=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SCPYZUAEPUWQKQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- BTKNEPOTETXVAE-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[3-(2-methoxyphenyl)pyridin-4-yl]-n,2-dimethylpropanamide Chemical compound COC1=CC=CC=C1C1=CN=CC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BTKNEPOTETXVAE-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- IHTFHQQTYOIZOZ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(2-chlorophenyl)-n-methylpyridine-4-carboxamide Chemical compound C=1C=NC=C(C=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IHTFHQQTYOIZOZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 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
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 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 description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 239000000243 solution Substances 0.000 description 57
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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 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 16
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000013078 crystal Substances 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 102100024304 Protachykinin-1 Human genes 0.000 description 9
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- FFVZOVSQIUBVSK-UHFFFAOYSA-N n-methyl-2-(2-methylphenyl)pyridin-4-amine Chemical compound CNC1=CC=NC(C=2C(=CC=CC=2)C)=C1 FFVZOVSQIUBVSK-UHFFFAOYSA-N 0.000 description 1
- FIEHZAKKSDHCAY-UHFFFAOYSA-N n-methyl-3-(2-methylphenyl)pyridin-4-amine Chemical compound CNC1=CC=NC=C1C1=CC=CC=C1C FIEHZAKKSDHCAY-UHFFFAOYSA-N 0.000 description 1
- LSCYTCMNCWMCQE-UHFFFAOYSA-N n-methylpyridin-4-amine Chemical compound CNC1=CC=NC=C1 LSCYTCMNCWMCQE-UHFFFAOYSA-N 0.000 description 1
- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 1
- 108010072906 phosphoramidon Proteins 0.000 description 1
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- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
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- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002466 tachykinin receptor agonist Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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- 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
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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
- 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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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (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 |
|---|---|---|---|
| EP99103503 | 1999-02-24 | ||
| PCT/EP2000/001223 WO2000050401A1 (en) | 1999-02-24 | 2000-02-15 | 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20010604A2 true HRP20010604A2 (en) | 2002-08-31 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20010604A HRP20010604A2 (en) | 1999-02-24 | 2001-08-14 | 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists |
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| MA (1) | MA26773A1 (cs) |
| MY (1) | MY122630A (cs) |
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| SI (1) | SI1157005T1 (cs) |
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| GB9928222D0 (en) * | 1999-11-30 | 2000-01-26 | Univ Sheffield | Chiral catalysts for asymmetric acylation and related transformations |
| AUPQ514600A0 (en) | 2000-01-18 | 2000-02-10 | James Cook University | Brain injury treatment |
| TWI287003B (en) * | 2000-07-24 | 2007-09-21 | Hoffmann La Roche | 4-phenyl-pyridine derivatives |
| SE0004245D0 (sv) | 2000-11-20 | 2000-11-20 | Pharmacia Ab | Novel compounds and their use |
| DE60142355D1 (de) * | 2000-11-20 | 2010-07-22 | Biovitrum Ab Publ | Piperazinylpyrazinverbindungen als agonisten oder antagonisten am serotonin-5ht-2-rezeptor |
| US20030083345A1 (en) * | 2001-07-10 | 2003-05-01 | Torsten Hoffmann | Method of treatment and/or prevention of brain, spinal or nerve injury |
| US7176322B2 (en) * | 2002-05-23 | 2007-02-13 | Amgen Inc. | Calcium receptor modulating agents |
| US6908935B2 (en) * | 2002-05-23 | 2005-06-21 | Amgen Inc. | Calcium receptor modulating agents |
| WO2004026823A1 (en) * | 2002-09-20 | 2004-04-01 | Pfizer Products Inc. | Amide and sulfonamide ligands for the estrogen receptor |
| CN101128189A (zh) | 2005-02-25 | 2008-02-20 | 弗·哈夫曼-拉罗切有限公司 | 药物物质分散性改善的片剂 |
| KR101331768B1 (ko) | 2005-11-08 | 2013-11-22 | 버텍스 파마슈티칼스 인코포레이티드 | Ａｔｐ 결합 카세트 수송체의 헤테로사이클릭 조정제 |
| US7671221B2 (en) | 2005-12-28 | 2010-03-02 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| US7754739B2 (en) | 2007-05-09 | 2010-07-13 | Vertex Pharmaceuticals Incorporated | Modulators of CFTR |
| US20080275085A1 (en) * | 2007-04-24 | 2008-11-06 | Junya Shirai | Piperidine derivative and use thereof |
| WO2008141119A2 (en) | 2007-05-09 | 2008-11-20 | Vertex Pharmaceuticals Incorporated | Modulators of cftr |
| SG186638A1 (en) | 2007-12-07 | 2013-01-30 | Vertex Pharma | Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3] dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid |
| KR20150066608A (ko) | 2007-12-07 | 2015-06-16 | 버텍스 파마슈티칼스 인코포레이티드 | 사이클로알킬카복시아미도-피리딘 벤조산의 제조 방법 |
| CA2716109C (en) | 2008-02-28 | 2016-07-19 | Vertex Pharmaceuticals Incorporated | Heteroaryl derivatives as cftr modulators |
| KR100943878B1 (ko) * | 2008-07-11 | 2010-02-24 | 오토스테크 주식회사 | 디지털방식 눈부심 방지 장치 및 그 제어 방법 |
| EP2350010B1 (en) * | 2008-10-30 | 2014-03-26 | Merck Sharp & Dohme Corp. | Isonicotinamide orexin receptor antagonists |
| JP5654608B2 (ja) * | 2009-11-17 | 2015-01-14 | ノバルティス アーゲー | アルドステロンシンターゼ阻害剤としてのアリール−ピリジン誘導体 |
| RU2592368C2 (ru) | 2010-04-07 | 2016-07-20 | Вертекс Фармасьютикалз Инкорпорейтед | ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, ВКЛЮЧАЮЩИЕ 3-(2, 2-ДИФТОРБЕНЗО[d][1, 3]ДИОКСОЛ-5-ИЛ)ЦИКЛОПРОПАНКАРБОКСАМИДО)-3-МЕТИЛПИРИДИН-2-ИЛ)БЕНЗОЙНУЮ КИСЛОТУ, И ИХ ВВЕДЕНИЕ |
| US8410107B2 (en) * | 2010-10-15 | 2013-04-02 | Hoffmann-La Roche Inc. | N-pyridin-3-yl or N-pyrazin-2-yl carboxamides |
| EP3067349B1 (en) | 2013-11-08 | 2018-02-28 | Kissei Pharmaceutical Co., Ltd. | Carboxymethyl piperidine derivative |
| AU2014349010C1 (en) | 2013-11-12 | 2020-08-06 | Vertex Pharmaceuticals Incorporated | Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases |
| TWI649307B (zh) | 2014-05-07 | 2019-02-01 | 日商橘生藥品工業股份有限公司 | Cyclohexylpyridine derivative |
| JP6494757B2 (ja) | 2014-11-18 | 2019-04-03 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | ハイスループット試験高速液体クロマトグラフィーを行うプロセス |
| EP3393519A1 (en) | 2015-12-22 | 2018-10-31 | Takeda Pharmaceutical Company Limited | Tripartite modulators of endosomal g protein-coupled receptors |
| JP2023538713A (ja) | 2020-05-06 | 2023-09-11 | バイエル、アクチエンゲゼルシャフト | 殺真菌性化合物としてのピリジン（チオ）アミド |
| EP4161914A1 (en) | 2020-06-04 | 2023-04-12 | Bayer Aktiengesellschaft | Heterocyclyl pyridines as novel fungicides |
| WO2023099445A1 (en) | 2021-11-30 | 2023-06-08 | Bayer Aktiengesellschaft | Bis(hetero)aryl thioether oxadiazines as fungicidal compounds |
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| US4174209A (en) * | 1978-06-19 | 1979-11-13 | Eli Lilly And Company | Herbicidal 1-alkyl-3-phenylpyridinium salts |
| IL111960A (en) | 1993-12-17 | 1999-12-22 | Merck & Co Inc | Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them |
| ATE278687T1 (de) | 1993-12-29 | 2004-10-15 | Merck Sharp & Dohme | Substituierte morpholinderivate und ihre verwendung als therapeutische mittel |
| IL112778A0 (en) | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
| DE69628484T2 (de) * | 1995-03-24 | 2004-05-19 | Takeda Chemical Industries, Ltd. | Zyklische Verbindungen, ihre Herstellung und ihre Verwendung als Tachykininrezeptorantagonisten |
| US5972938A (en) | 1997-12-01 | 1999-10-26 | Merck & Co., Inc. | Method for treating or preventing psychoimmunological disorders |
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2000
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