HRP20010603A2 - Phenyl-and pyridinyl derivatives - Google Patents
Phenyl-and pyridinyl derivatives Download PDFInfo
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- HRP20010603A2 HRP20010603A2 HR20010603A HRP20010603A HRP20010603A2 HR P20010603 A2 HRP20010603 A2 HR P20010603A2 HR 20010603 A HR20010603 A HR 20010603A HR P20010603 A HRP20010603 A HR P20010603A HR P20010603 A2 HRP20010603 A2 HR P20010603A2
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- Prior art keywords
- compound
- phenyl
- methyl
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- 125000004076 pyridyl group Chemical group 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 160
- 238000000034 method Methods 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- -1 cyclic tertiary amine Chemical class 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- CVNRYRCGBTUCFY-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-6-morpholin-4-yl-4-phenoxypyridine-3-carboxamide Chemical compound C=1N=C(N2CCOCC2)C=C(OC=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CVNRYRCGBTUCFY-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 8
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims description 8
- HLFSMLPUTRFVHR-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-methyl-n-[2-(n-methylanilino)phenyl]propanamide Chemical compound C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(C)C(=O)N(C)C1=CC=CC=C1N(C)C1=CC=CC=C1 HLFSMLPUTRFVHR-UHFFFAOYSA-N 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 229940044551 receptor antagonist Drugs 0.000 claims description 5
- 239000002464 receptor antagonist Substances 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- LUXURCGHCPQELB-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[2-(2-methylphenoxy)phenyl]propanamide Chemical compound C=1C=CC=C(OC=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 LUXURCGHCPQELB-UHFFFAOYSA-N 0.000 claims description 3
- UQPNOJMVYMYAAK-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-(2,4-dichlorophenoxy)phenyl]-n,2-dimethylpropanamide Chemical compound C=1C=CC=C(OC=2C(=CC(Cl)=CC=2)Cl)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UQPNOJMVYMYAAK-UHFFFAOYSA-N 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 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 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- WEFSUSLWPKZJRX-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorophenoxy)-n-methyl-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WEFSUSLWPKZJRX-UHFFFAOYSA-N 0.000 claims description 3
- KCFLOTGOYFKTDU-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorophenoxy)-n-methyl-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCOCC2)C=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KCFLOTGOYFKTDU-UHFFFAOYSA-N 0.000 claims description 3
- VQEPVISZVOXBHJ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCOCC2)C=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VQEPVISZVOXBHJ-UHFFFAOYSA-N 0.000 claims description 3
- DOPMDLBAWFYRLG-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-(n-methylanilino)phenyl]acetamide Chemical compound C=1C=CC=C(NC(=O)CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=1N(C)C1=CC=CC=C1 DOPMDLBAWFYRLG-UHFFFAOYSA-N 0.000 claims description 2
- FYINLBOSVUIIOT-UHFFFAOYSA-N 4-benzoyl-n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C(=O)C=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FYINLBOSVUIIOT-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 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
- 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
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- NWFQMSVOTMMNET-UHFFFAOYSA-N n-[2-benzoyl-4-(4-methylpiperazin-1-yl)phenyl]-2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanamide Chemical compound C1CN(C)CCN1C(C=C1C(=O)C=2C=CC=CC=2)=CC=C1NC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NWFQMSVOTMMNET-UHFFFAOYSA-N 0.000 claims description 2
- RCDCKKVXQMPIPK-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorobenzoyl)-n-methyl-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C(=O)C=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RCDCKKVXQMPIPK-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
- 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 5
- 201000010099 disease Diseases 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 239000000203 mixture Substances 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 102100024304 Protachykinin-1 Human genes 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 239000000829 suppository Substances 0.000 description 8
- JBCUKQQIWSWEOK-UHFFFAOYSA-N 2-(benzenesulfonyl)aniline Chemical compound NC1=CC=CC=C1S(=O)(=O)C1=CC=CC=C1 JBCUKQQIWSWEOK-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 101800003906 Substance P Proteins 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 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 6
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- 239000000047 product Substances 0.000 description 6
- ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 5
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- SFEVQUPISPQHOG-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl chloride Chemical compound ClC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SFEVQUPISPQHOG-UHFFFAOYSA-N 0.000 description 4
- UWMLRAHCCDRPRJ-UHFFFAOYSA-N 2-benzyl-n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methylbenzamide Chemical compound C=1C=CC=C(CC=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UWMLRAHCCDRPRJ-UHFFFAOYSA-N 0.000 description 4
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- IZSZQQABJVGIFJ-UHFFFAOYSA-N (2-amino-2-methylpropyl) 4-benzoyl-6-(4-methylpiperazin-1-yl)pyridine-3-carboxylate Chemical compound C1CN(C)CCN1C1=CC(C(=O)C=2C=CC=CC=2)=C(C(=O)OCC(C)(C)N)C=N1 IZSZQQABJVGIFJ-UHFFFAOYSA-N 0.000 description 2
- WXEOPBYWJZTKGV-UHFFFAOYSA-N (3-aminopyridin-4-yl)-phenylmethanone Chemical compound NC1=CN=CC=C1C(=O)C1=CC=CC=C1 WXEOPBYWJZTKGV-UHFFFAOYSA-N 0.000 description 2
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- C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/29—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/30—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
- C07C233/33—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/44—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
- C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
- C07C317/40—Y being a hydrogen or a carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/40—Y being a hydrogen or a carbon atom
- C07C323/41—Y being a hydrogen or an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Otolaryngology (AREA)
- Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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EP99103502 | 1999-02-24 | ||
PCT/EP2000/001224 WO2000050398A2 (en) | 1999-02-24 | 2000-02-15 | Phenyl- and pyridinyl derivatives as neurokinin 1 antagonists |
Publications (1)
Publication Number | Publication Date |
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HRP20010603A2 true HRP20010603A2 (en) | 2002-08-31 |
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HR20010603A HRP20010603A2 (en) | 1999-02-24 | 2001-08-14 | Phenyl-and pyridinyl derivatives |
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JP (1) | JP4070957B2 (xx) |
KR (1) | KR100514236B1 (xx) |
CN (1) | CN1131212C (xx) |
AR (1) | AR044719A1 (xx) |
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AU (1) | AU767123B2 (xx) |
BR (1) | BR0008489A (xx) |
CA (1) | CA2364665C (xx) |
CO (1) | CO5140088A1 (xx) |
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DE (1) | DE60031513T2 (xx) |
ES (1) | ES2272264T3 (xx) |
HK (1) | HK1044941B (xx) |
HR (1) | HRP20010603A2 (xx) |
HU (1) | HUP0200124A3 (xx) |
IL (1) | IL144717A0 (xx) |
JO (1) | JO2244B1 (xx) |
MA (1) | MA26774A1 (xx) |
MY (1) | MY133237A (xx) |
NO (1) | NO320321B1 (xx) |
NZ (1) | NZ513322A (xx) |
PE (1) | PE20010009A1 (xx) |
PL (1) | PL350427A1 (xx) |
RU (1) | RU2238264C2 (xx) |
TR (1) | TR200102490T2 (xx) |
WO (1) | WO2000050398A2 (xx) |
YU (1) | YU59801A (xx) |
ZA (1) | ZA200106258B (xx) |
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TWI280239B (en) | 2003-07-15 | 2007-05-01 | Hoffmann La Roche | Process for preparation of pyridine derivatives |
MY139645A (en) * | 2004-02-11 | 2009-10-30 | Amgen Inc | Vanilloid receptor ligands and their use in treatments |
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ES2644450T3 (es) | 2004-12-31 | 2017-11-29 | Dr. Reddy's Laboratories Ltd. | Nuevos derivados de bencilamina como inhibidores de CETP |
WO2006089311A1 (en) * | 2005-02-15 | 2006-08-24 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
KR20070094666A (ko) | 2005-02-25 | 2007-09-20 | 에프. 호프만-라 로슈 아게 | 약제 물질 분산성이 향상된 정제 |
US20060235036A1 (en) * | 2005-04-15 | 2006-10-19 | Doherty Elizabeth M | Vanilloid receptor ligands and their use in treatments |
DK1928427T3 (da) | 2005-09-23 | 2010-03-08 | Hoffmann La Roche | Hidtil ukendt dosisformulering |
ES2439736T3 (es) | 2005-11-08 | 2014-01-24 | Vertex Pharmaceuticals Incorporated | Moduladores heterocíclicos de transportadores de casete de unión a ATP |
US7671221B2 (en) | 2005-12-28 | 2010-03-02 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
GB0603190D0 (en) * | 2006-02-16 | 2006-03-29 | Enigma Diagnostics Ltd | Detection system |
KR100932093B1 (ko) * | 2006-09-27 | 2009-12-16 | 주식회사종근당 | 미세소관 형성 저해제로서 유용한 벤조페논 유도체 |
MX2009003981A (es) * | 2006-10-26 | 2009-04-27 | Amgen Inc | Agentes moduladores del receptor de calcio. |
US7754739B2 (en) | 2007-05-09 | 2010-07-13 | Vertex Pharmaceuticals Incorporated | Modulators of CFTR |
CN104447716A (zh) | 2007-05-09 | 2015-03-25 | 沃泰克斯药物股份有限公司 | Cftr调节剂 |
WO2009051718A2 (en) * | 2007-10-15 | 2009-04-23 | Amgen Inc. | Calcium receptor modulating agents |
CN101910156B (zh) | 2007-12-07 | 2013-12-04 | 沃泰克斯药物股份有限公司 | 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的固体形式 |
CA2989620C (en) | 2007-12-07 | 2022-05-03 | Vertex Pharmaceuticals Incorporated | Processes for producing cycloalkylcarboxamido-pyridine benzoic acids |
EP2271622B1 (en) | 2008-02-28 | 2017-10-04 | Vertex Pharmaceuticals Incorporated | Heteroaryl derivatives as CFTR Modulators |
GB0808747D0 (en) | 2008-05-14 | 2008-06-18 | Glaxo Wellcome Mfg Pte Ltd | Novel compounds |
WO2010042642A1 (en) * | 2008-10-08 | 2010-04-15 | Amgen Inc. | Calcium receptor modulating agents |
JP2012529535A (ja) | 2009-06-12 | 2012-11-22 | ブリストル−マイヤーズ スクイブ カンパニー | キナーゼモジュレーターとして有用なニコチンアミド化合物 |
US8470820B2 (en) * | 2010-01-22 | 2013-06-25 | Hoffman-La Roche Inc. | Nitrogen-containing heteroaryl derivatives |
DK3150198T3 (da) | 2010-04-07 | 2021-11-01 | Vertex Pharma | Farmaceutiske sammensætninger af 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioxol-5-yl)-cyclopropancarboxamido)-3-methylpyriodin-2-yl)benzoesyre og indgivelse deraf |
DE102011007272A1 (de) | 2011-04-13 | 2012-10-18 | Bayer Pharma Aktiengesellschaft | Verzweigte 3-Phenylpropionsäure-Derivate und ihre Verwendung |
JP5964965B2 (ja) | 2011-08-18 | 2016-08-03 | ドクター レディズ ラボラトリーズ リミテッド | コレステリルエステル転送タンパク質(cetp)インヒビターとしての置換複素環式アミン化合物 |
MX352074B (es) | 2011-09-27 | 2017-11-08 | Dr Reddys Laboratories Ltd | Derivados de 5-bencilaminometil-6-aminopirazolo [3,4-b] piridina como inhibidores de proteina de transferencia de ester de colesterilo (cetp) utiles para el tratamiento de aterosclerosis. |
US10231932B2 (en) | 2013-11-12 | 2019-03-19 | Vertex Pharmaceuticals Incorporated | Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases |
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 |
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CN109678815B (zh) * | 2019-01-09 | 2022-11-29 | 中国药科大学 | N-苄基苯甲酰胺类衍生物及其制备方法与制药用途 |
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BR9408442A (pt) | 1993-12-29 | 1997-08-05 | Merck Sharp & Dohme | Composto composição farmacêutica processos para tratamento ou prevenção de distúrbios fisiológicos associados com um excesso de taquiquininas e para a preparação do composto e de uso do composto |
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US5972938A (en) | 1997-12-01 | 1999-10-26 | Merck & Co., Inc. | Method for treating or preventing psychoimmunological disorders |
AU2203800A (en) * | 1999-01-07 | 2000-07-24 | Warner-Lambert Company | Antiviral method using mek inhibitors |
ATE496032T1 (de) * | 1999-02-24 | 2011-02-15 | 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 |
DE60006340T2 (de) * | 1999-11-29 | 2004-09-09 | F. Hoffmann-La Roche Ag | 2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramid |
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2000
- 2000-02-15 TR TR2001/02490T patent/TR200102490T2/xx unknown
- 2000-02-15 CZ CZ20013046A patent/CZ20013046A3/cs unknown
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- 2000-02-15 DE DE60031513T patent/DE60031513T2/de not_active Expired - Lifetime
- 2000-02-15 AT AT00912462T patent/ATE343565T1/de not_active IP Right Cessation
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- 2000-02-15 WO PCT/EP2000/001224 patent/WO2000050398A2/en active IP Right Grant
- 2000-02-15 PL PL00350427A patent/PL350427A1/xx not_active Application Discontinuation
- 2000-02-15 KR KR10-2001-7010730A patent/KR100514236B1/ko not_active IP Right Cessation
- 2000-02-15 NZ NZ513322A patent/NZ513322A/en unknown
- 2000-02-15 EP EP00912462A patent/EP1157006B1/en not_active Expired - Lifetime
- 2000-02-15 CN CN00804240A patent/CN1131212C/zh not_active Expired - Fee Related
- 2000-02-15 JP JP2000600981A patent/JP4070957B2/ja not_active Expired - Fee Related
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- 2000-02-16 US US09/505,356 patent/US6407111B1/en not_active Expired - Fee Related
- 2000-02-18 PE PE2000000123A patent/PE20010009A1/es not_active Application Discontinuation
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- 2000-02-22 MY MYPI20000650A patent/MY133237A/en unknown
- 2000-02-22 CO CO00012296A patent/CO5140088A1/es unknown
- 2000-02-23 AR ARP000100755A patent/AR044719A1/es unknown
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2001
- 2001-07-30 ZA ZA200106258A patent/ZA200106258B/en unknown
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- 2001-08-23 MA MA26302A patent/MA26774A1/fr unknown
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2002
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