ME00593B - Derivati 4-fenil-piridina - Google Patents
Derivati 4-fenil-piridinaInfo
- Publication number
- ME00593B ME00593B MEP-2009-57A MEP5709A ME00593B ME 00593 B ME00593 B ME 00593B ME P5709 A MEP5709 A ME P5709A ME 00593 B ME00593 B ME 00593B
- Authority
- ME
- Montenegro
- Prior art keywords
- methyl
- tolyl
- nicotinamide
- trifluoromethyl
- benzyl
- Prior art date
Links
- 150000005362 4-phenylpyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 87
- 238000000034 method Methods 0.000 claims description 31
- -1 C1-7-alkoxy Chemical class 0.000 claims description 24
- FMQPGFVLWDLWPR-UHFFFAOYSA-N n-methyl-n-[(2-methylnaphthalen-1-yl)methyl]-4-(2-methylphenyl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound CC=1C=CC2=CC=CC=C2C=1CN(C)C(=O)C1=CN=C(N2CCOCC2)C=C1C1=CC=CC=C1C FMQPGFVLWDLWPR-UHFFFAOYSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 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
- HCNNJLLLMSVTFH-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical group C=1N=C(N2CCN(C)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 HCNNJLLLMSVTFH-UHFFFAOYSA-N 0.000 claims description 7
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims description 6
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- HZBSJCLPYPJTHM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-piperazin-1-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCNCC2)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 HZBSJCLPYPJTHM-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- WLFSWIPBWCLJIG-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CCO)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 WLFSWIPBWCLJIG-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229940044551 receptor antagonist Drugs 0.000 claims description 4
- 239000002464 receptor antagonist Substances 0.000 claims description 4
- 150000003512 tertiary amines Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- GLWUUJAEACZDNZ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-(4-formylpiperazin-1-yl)-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CC2)C=O)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 GLWUUJAEACZDNZ-UHFFFAOYSA-N 0.000 claims description 3
- VQHCPDADMQPSJL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CCOCCO)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 VQHCPDADMQPSJL-UHFFFAOYSA-N 0.000 claims description 3
- HINABYJPTBAFEL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(4-propylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C1CN(CCC)CCN1C1=CC(C=2C(=CC=CC=2)C)=C(C(=O)N(C)CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=N1 HINABYJPTBAFEL-UHFFFAOYSA-N 0.000 claims description 3
- SXYYITYNMZNYQV-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-[4-[(5-oxo-1,2-dihydro-1,2,4-triazol-3-yl)methyl]piperazin-1-yl]pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CC=3NC(=O)NN=3)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 SXYYITYNMZNYQV-UHFFFAOYSA-N 0.000 claims description 3
- DGRVWNYJJZUMSS-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCOCC2)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 DGRVWNYJJZUMSS-UHFFFAOYSA-N 0.000 claims description 3
- QYTHSLPCLPLAQP-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-6-[methyl(2-morpholin-4-ylethyl)amino]-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N(C)CCN2CCOCC2)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 QYTHSLPCLPLAQP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([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
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- MUQYNWRDIOWJMA-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(1-oxo-1,4-thiazinan-4-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCS(=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 MUQYNWRDIOWJMA-UHFFFAOYSA-N 0.000 claims description 2
- ZFUYBRRKEVIJEB-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-6-(4-methylpiperazin-1-yl)-4-naphthalen-1-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C3=CC=CC=C3C=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZFUYBRRKEVIJEB-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
- 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
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- DLESBWMTMZQQDE-UHFFFAOYSA-N 1-[5-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-4-(2-methylphenyl)pyridin-2-yl]piperidine-4-carboxylic acid Chemical class C=1N=C(N2CCC(CC2)C(O)=O)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 DLESBWMTMZQQDE-UHFFFAOYSA-N 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 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 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000000203 mixture Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 13
- AREZHNGVHWLGSF-UHFFFAOYSA-N 4-[5-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-4-(2-methylphenyl)pyridin-2-yl]piperazine-1-carboxylic acid Chemical class C=1N=C(N2CCN(CC2)C(O)=O)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 AREZHNGVHWLGSF-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 102100024304 Protachykinin-1 Human genes 0.000 description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- STBYRSZXHDPASK-UHFFFAOYSA-N 1-(chloromethyl)-2-methylnaphthalene Chemical compound C1=CC=CC2=C(CCl)C(C)=CC=C21 STBYRSZXHDPASK-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 101800003906 Substance P Proteins 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229960003966 nicotinamide Drugs 0.000 description 9
- 239000011570 nicotinamide Substances 0.000 description 9
- 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
- 238000001035 drying Methods 0.000 description 8
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 206010047700 Vomiting Diseases 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- QNQKCTPOGILUGX-UHFFFAOYSA-N 4-[5-(methylcarbamoyl)-4-(2-methylphenyl)pyridin-2-yl]piperazine-1-carboxylic acid Chemical class CNC(=O)C1=CN=C(N2CCN(CC2)C(O)=O)C=C1C1=CC=CC=C1C QNQKCTPOGILUGX-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- BMXZBYOYLNTJRL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-thiomorpholin-4-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCSCC2)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 BMXZBYOYLNTJRL-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 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 4
- 238000010992 reflux Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 230000008673 vomiting Effects 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- FCYRBVQBKKBPKD-UHFFFAOYSA-N n-methyl-4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound CNC(=O)C1=CN=C(N2CCN(C)CC2)C=C1C1=CC=CC=C1C FCYRBVQBKKBPKD-UHFFFAOYSA-N 0.000 description 3
- 239000002742 neurokinin 1 receptor antagonist Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000002462 tachykinin receptor antagonist Substances 0.000 description 3
- VEMXLMPSJAQQBW-UHFFFAOYSA-N tert-butyl 4-[5-(methylcarbamoyl)-4-(2-methylphenyl)pyridin-2-yl]piperazine-1-carboxylate Chemical compound CNC(=O)C1=CN=C(N2CCN(CC2)C(=O)OC(C)(C)C)C=C1C1=CC=CC=C1C VEMXLMPSJAQQBW-UHFFFAOYSA-N 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 2
- ATLQGZVLWOURFU-UHFFFAOYSA-N 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(CBr)=CC(C(F)(F)F)=C1 ATLQGZVLWOURFU-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- XGXZBEAMIBKQHL-UHFFFAOYSA-N 4-iodo-n-methyl-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C1=C(I)C(C(=O)NC)=CN=C1N1CCN(C)CC1 XGXZBEAMIBKQHL-UHFFFAOYSA-N 0.000 description 2
- GXMHAZCHUPKETI-UHFFFAOYSA-N 6-chloro-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound CNC(=O)C1=CN=C(Cl)C=C1C1=CC=CC=C1C GXMHAZCHUPKETI-UHFFFAOYSA-N 0.000 description 2
- DEYOMDZKXMQLCF-UHFFFAOYSA-N 6-chloro-n-methylpyridine-3-carboxamide Chemical compound CNC(=O)C1=CC=C(Cl)N=C1 DEYOMDZKXMQLCF-UHFFFAOYSA-N 0.000 description 2
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- 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
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- XDEPVFFKOVDUNO-UHFFFAOYSA-N pentafluorobenzyl bromide Chemical compound FC1=C(F)C(F)=C(CBr)C(F)=C1F XDEPVFFKOVDUNO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
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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
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- 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
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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
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—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 chain containing hetero atoms as chain links
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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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EP99103504 | 1999-02-24 | ||
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2000
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