PT2318375E - Imidazole carboxamidas - Google Patents
Imidazole carboxamidas Download PDFInfo
- Publication number
- PT2318375E PT2318375E PT09790351T PT09790351T PT2318375E PT 2318375 E PT2318375 E PT 2318375E PT 09790351 T PT09790351 T PT 09790351T PT 09790351 T PT09790351 T PT 09790351T PT 2318375 E PT2318375 E PT 2318375E
- Authority
- PT
- Portugal
- Prior art keywords
- methyl
- compound
- trifluoromethyl
- mmol
- pharmaceutically acceptable
- Prior art date
Links
- NMIZONYLXCOHEF-UHFFFAOYSA-N 1h-imidazole-2-carboxamide Chemical class NC(=O)C1=NC=CN1 NMIZONYLXCOHEF-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 166
- 150000003839 salts Chemical class 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 14
- 150000002431 hydrogen Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 208000020401 Depressive disease Diseases 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims 6
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 2
- SKNNATYDYVUYGI-UHFFFAOYSA-N CC(C)C(C(C=CC(OCC1=CC=C(CN)C=C1)=C1C(F)(F)F)=C1O)=O.CN1C=NC(C(O)=O)=C1 Chemical compound CC(C)C(C(C=CC(OCC1=CC=C(CN)C=C1)=C1C(F)(F)F)=C1O)=O.CN1C=NC(C(O)=O)=C1 SKNNATYDYVUYGI-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- QCGGXGCODUUTLZ-UHFFFAOYSA-N [Na].[Na].[Na].[Na] Chemical compound [Na].[Na].[Na].[Na] QCGGXGCODUUTLZ-UHFFFAOYSA-N 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- RDOVSPPEPGMKEB-UHFFFAOYSA-L trisodium;sulfate Chemical compound [Na+].[Na+].[Na+].[O-]S([O-])(=O)=O RDOVSPPEPGMKEB-UHFFFAOYSA-L 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 164
- 238000001819 mass spectrum Methods 0.000 description 156
- -1 IMIDAZOLE CARBOXAMIDES Chemical class 0.000 description 84
- 238000002360 preparation method Methods 0.000 description 74
- 239000011541 reaction mixture Substances 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 42
- 239000000243 solution Substances 0.000 description 41
- 239000007787 solid Substances 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- 239000012458 free base Substances 0.000 description 35
- 238000000034 method Methods 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- 239000012267 brine Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 230000004044 response Effects 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000000126 substance Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 229910052938 sodium sulfate Inorganic materials 0.000 description 25
- 235000011152 sodium sulphate Nutrition 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- 239000012141 concentrate Substances 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 238000007792 addition Methods 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 208000019901 Anxiety disease Diseases 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 230000036506 anxiety Effects 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 230000036760 body temperature Effects 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- 206010020843 Hyperthermia Diseases 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 230000036031 hyperthermia Effects 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 230000002787 reinforcement Effects 0.000 description 6
- NYFNJYJWOHQAMU-UHFFFAOYSA-N 1-[2,4-dihydroxy-3-(trifluoromethyl)phenyl]-2-methylpropan-1-one Chemical compound CC(C)C(=O)C1=CC=C(O)C(C(F)(F)F)=C1O NYFNJYJWOHQAMU-UHFFFAOYSA-N 0.000 description 5
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 238000012002 interactive response technology Methods 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000001931 thermography Methods 0.000 description 5
- WZTRQGJMMHMFGH-UHFFFAOYSA-N 1-methyl-imidazole-4-carboxylic acid Chemical compound CN1C=NC(C(O)=O)=C1 WZTRQGJMMHMFGH-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- 208000011688 Generalised anxiety disease Diseases 0.000 description 4
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 4
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 208000029364 generalized anxiety disease Diseases 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 4
- 229910052808 lithium carbonate Inorganic materials 0.000 description 4
- 208000024714 major depressive disease Diseases 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000010926 purge Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 4
- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 3
- UIAJWNXLQAGBMA-UHFFFAOYSA-N 1-[2,4-bis(phenylmethoxy)-3-(trifluoromethyl)phenyl]-2-methylpropan-1-one Chemical compound FC(F)(F)C1=C(OCC=2C=CC=CC=2)C(C(=O)C(C)C)=CC=C1OCC1=CC=CC=C1 UIAJWNXLQAGBMA-UHFFFAOYSA-N 0.000 description 3
- ZZHILWYVFMYBGD-UHFFFAOYSA-N 1-[4-[[4-(aminomethyl)phenyl]methoxy]-2-hydroxy-3-(trifluoromethyl)phenyl]-2-methylpropan-1-one;hydrochloride Chemical compound Cl.FC(F)(F)C1=C(O)C(C(=O)C(C)C)=CC=C1OCC1=CC=C(CN)C=C1 ZZHILWYVFMYBGD-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000005909 Kieselgur Substances 0.000 description 3
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 3
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- GNSCYCNQOANMTI-UHFFFAOYSA-N [6-(aminomethyl)pyridin-3-yl]methanol Chemical compound NCC1=CC=C(CO)C=N1 GNSCYCNQOANMTI-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000010779 crude oil Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229960002464 fluoxetine Drugs 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- NLSUCNKNEPJLAV-UHFFFAOYSA-N methyl 1-tritylimidazole-4-carboxylate Chemical compound C1=NC(C(=O)OC)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 NLSUCNKNEPJLAV-UHFFFAOYSA-N 0.000 description 3
- UAYKHVMBFFBZFI-UHFFFAOYSA-N methyl 6-(chloromethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CCl)N=C1 UAYKHVMBFFBZFI-UHFFFAOYSA-N 0.000 description 3
- QVLONHSXRWCCAE-UHFFFAOYSA-N methyl 6-(hydroxymethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CO)N=C1 QVLONHSXRWCCAE-UHFFFAOYSA-N 0.000 description 3
- AMCABIVMXHPLIT-UHFFFAOYSA-N n-[[4-(iodomethyl)phenyl]methyl]-1-methylimidazole-4-carboxamide Chemical compound CN1C=NC(C(=O)NCC=2C=CC(CI)=CC=2)=C1 AMCABIVMXHPLIT-UHFFFAOYSA-N 0.000 description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
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- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
- KZPZTVKOJSKVBV-UHFFFAOYSA-N methyl 1-methylimidazole-4-carboxylate Chemical compound COC(=O)C1=CN(C)C=N1 KZPZTVKOJSKVBV-UHFFFAOYSA-N 0.000 description 1
- DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 description 1
- AVNQOBATVQLYET-UHFFFAOYSA-N methyl 2-chloro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=C(CNC(=O)OC(C)(C)C)C=C1Cl AVNQOBATVQLYET-UHFFFAOYSA-N 0.000 description 1
- PJZFAIKANVMKKU-UHFFFAOYSA-N methyl 2-chloro-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1Cl PJZFAIKANVMKKU-UHFFFAOYSA-N 0.000 description 1
- KTFQDZCNPGFKAH-UHFFFAOYSA-N methyl 3-chloro-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(Cl)=C1 KTFQDZCNPGFKAH-UHFFFAOYSA-N 0.000 description 1
- WAGSGHIIJKPOHK-UHFFFAOYSA-N methyl 3-methyl-4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=C(CNC(=O)OC(C)(C)C)C(C)=C1 WAGSGHIIJKPOHK-UHFFFAOYSA-N 0.000 description 1
- LCAZFABQXUTCSK-UHFFFAOYSA-N methyl 3-methyl-4-[[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]benzoate Chemical compound COC(=O)C1=CC=C(CN(C)C(=O)OC(C)(C)C)C(C)=C1 LCAZFABQXUTCSK-UHFFFAOYSA-N 0.000 description 1
- XPIUJBSUFHGVHI-UHFFFAOYSA-N methyl 4-(aminomethyl)-2,3-difluorobenzoate Chemical compound COC(=O)C1=CC=C(CN)C(F)=C1F XPIUJBSUFHGVHI-UHFFFAOYSA-N 0.000 description 1
- GGAFQXNKBHDZLI-UHFFFAOYSA-N methyl 4-(aminomethyl)-2-fluorobenzoate Chemical compound COC(=O)C1=CC=C(CN)C=C1F GGAFQXNKBHDZLI-UHFFFAOYSA-N 0.000 description 1
- GNBQLMBPFKIXJX-UHFFFAOYSA-N methyl 4-(aminomethyl)-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CN)C=C1OC GNBQLMBPFKIXJX-UHFFFAOYSA-N 0.000 description 1
- VXLLMVXXEXMLNL-UHFFFAOYSA-N methyl 4-(aminomethyl)-3-chlorobenzoate Chemical compound COC(=O)C1=CC=C(CN)C(Cl)=C1 VXLLMVXXEXMLNL-UHFFFAOYSA-N 0.000 description 1
- NNOBUPILNNMONK-UHFFFAOYSA-N methyl 4-(aminomethyl)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CN)C(OC)=C1 NNOBUPILNNMONK-UHFFFAOYSA-N 0.000 description 1
- CYGJEWIECWOXNH-UHFFFAOYSA-N methyl 4-(aminomethyl)-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(CN)C(C)=C1 CYGJEWIECWOXNH-UHFFFAOYSA-N 0.000 description 1
- TXWZNEPFUMOXPP-UHFFFAOYSA-N methyl 4-(azidomethyl)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CN=[N+]=[N-])C(OC)=C1 TXWZNEPFUMOXPP-UHFFFAOYSA-N 0.000 description 1
- DKTXXBLWUUYFNL-UHFFFAOYSA-N methyl 4-(bromomethyl)-2,3-difluorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(F)=C1F DKTXXBLWUUYFNL-UHFFFAOYSA-N 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- HDIWYFOUSUGFLF-UHFFFAOYSA-N n-[[2,3-difluoro-4-[[3-hydroxy-4-(2-methylpropanoyl)-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]-1-methylimidazole-4-carboxamide Chemical compound FC(F)(F)C1=C(O)C(C(=O)C(C)C)=CC=C1OCC(C(=C1F)F)=CC=C1CNC(=O)C1=CN(C)C=N1 HDIWYFOUSUGFLF-UHFFFAOYSA-N 0.000 description 1
- FGYPRXRXTADDTR-UHFFFAOYSA-N n-[[2-chloro-4-[[3-hydroxy-4-(2-methylpropanoyl)-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]-1-methylimidazole-4-carboxamide Chemical compound FC(F)(F)C1=C(O)C(C(=O)C(C)C)=CC=C1OCC(C=C1Cl)=CC=C1CNC(=O)C1=CN(C)C=N1 FGYPRXRXTADDTR-UHFFFAOYSA-N 0.000 description 1
- QMRIRVBALXSKSE-UHFFFAOYSA-N n-[[3-[[4-acetyl-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]-n,3-dimethylimidazole-4-carboxamide Chemical compound C=1N=CN(C)C=1C(=O)N(C)CC(C=1)=CC=CC=1COC1=CC=C(C(C)=O)C(O)=C1C(F)(F)F QMRIRVBALXSKSE-UHFFFAOYSA-N 0.000 description 1
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- MKYANLSHZXGNJT-UHFFFAOYSA-N n-[[4-[[4-(cyclopentanecarbonyl)-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]-1-methylimidazole-4-carboxamide Chemical compound CN1C=NC(C(=O)NCC=2C=CC(COC=3C(=C(O)C(C(=O)C4CCCC4)=CC=3)C(F)(F)F)=CC=2)=C1 MKYANLSHZXGNJT-UHFFFAOYSA-N 0.000 description 1
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
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- 229920000656 polylysine Polymers 0.000 description 1
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- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
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- 230000003389 potentiating effect Effects 0.000 description 1
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- 150000003254 radicals Chemical class 0.000 description 1
- CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 1
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
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- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
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- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- BOCWGBMVJKSUOD-UHFFFAOYSA-N tert-butyl 1h-imidazole-5-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=CN1 BOCWGBMVJKSUOD-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- NFHDHPLNCCIKPF-UHFFFAOYSA-N tert-butyl n-[[3-(hydroxymethyl)phenyl]methyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=CC=CC(CO)=C1 NFHDHPLNCCIKPF-UHFFFAOYSA-N 0.000 description 1
- QNDFFICIIGQGDV-UHFFFAOYSA-N tert-butyl n-[[3-(hydroxymethyl)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(CO)=C1 QNDFFICIIGQGDV-UHFFFAOYSA-N 0.000 description 1
- JFXAHPWMRAOYGV-UHFFFAOYSA-N tert-butyl n-[[3-(iodomethyl)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(CI)=C1 JFXAHPWMRAOYGV-UHFFFAOYSA-N 0.000 description 1
- BIHMLEFRUOZAOB-UHFFFAOYSA-N tert-butyl n-[[3-[[4-acetyl-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]carbamate Chemical compound FC(F)(F)C1=C(O)C(C(=O)C)=CC=C1OCC1=CC=CC(CNC(=O)OC(C)(C)C)=C1 BIHMLEFRUOZAOB-UHFFFAOYSA-N 0.000 description 1
- PDMDQEVZJFWYLS-UHFFFAOYSA-N tert-butyl n-[[4-[[4-(2-cyclopropylacetyl)-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1COC(C(=C1O)C(F)(F)F)=CC=C1C(=O)CC1CC1 PDMDQEVZJFWYLS-UHFFFAOYSA-N 0.000 description 1
- ODSPNWKLTCAOTM-UHFFFAOYSA-N tert-butyl n-[[4-[[4-(cyclobutanecarbonyl)-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1COC(C(=C1O)C(F)(F)F)=CC=C1C(=O)C1CCC1 ODSPNWKLTCAOTM-UHFFFAOYSA-N 0.000 description 1
- KIOHVWNAAOEGRB-UHFFFAOYSA-N tert-butyl n-[[4-[[4-(cyclopentanecarbonyl)-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1COC(C(=C1O)C(F)(F)F)=CC=C1C(=O)C1CCCC1 KIOHVWNAAOEGRB-UHFFFAOYSA-N 0.000 description 1
- VGIDHHRUTLKSPP-UHFFFAOYSA-N tert-butyl n-[[4-[[4-(cyclopropanecarbonyl)-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1COC(C(=C1O)C(F)(F)F)=CC=C1C(=O)C1CC1 VGIDHHRUTLKSPP-UHFFFAOYSA-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
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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Classifications
-
- 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
- C07D233/66—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 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
-
- 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
- C07D233/66—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 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
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Developing Agents For Electrophotography (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8177408P | 2008-07-18 | 2008-07-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2318375E true PT2318375E (pt) | 2012-10-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT09790351T PT2318375E (pt) | 2008-07-18 | 2009-07-14 | Imidazole carboxamidas |
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|---|---|
| US (1) | US7754742B2 (https=) |
| EP (1) | EP2318375B1 (https=) |
| JP (1) | JP5379227B2 (https=) |
| KR (1) | KR101287713B1 (https=) |
| CN (1) | CN102099344B (https=) |
| AR (1) | AR074631A1 (https=) |
| BR (1) | BRPI0915977A2 (https=) |
| CA (1) | CA2731215C (https=) |
| CY (1) | CY1113315T1 (https=) |
| DK (1) | DK2318375T3 (https=) |
| EA (1) | EA018434B1 (https=) |
| ES (1) | ES2393243T3 (https=) |
| HR (1) | HRP20120830T1 (https=) |
| MX (1) | MX2011000611A (https=) |
| PL (1) | PL2318375T3 (https=) |
| PT (1) | PT2318375E (https=) |
| SI (1) | SI2318375T1 (https=) |
| TW (1) | TW201006801A (https=) |
| WO (1) | WO2010009062A1 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI417095B (zh) | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | １，４-二取代之３-氰基-吡啶酮衍生物及其作為ｍＧｌｕＲ２-受體之正向異位性調節劑之用途 |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| US8722894B2 (en) | 2007-09-14 | 2014-05-13 | Janssen Pharmaceuticals, Inc. | 1,3-disubstituted-4-phenyl-1H-pyridin-2-ones |
| PL2203439T3 (pl) | 2007-09-14 | 2011-06-30 | Addex Pharmaceuticals Sa | 1',3'-dipodstawione-4-fenylo-3,4,5,6-tetrahydro-2H, 1'H-[1, 4']bipirydynylo-2'-ketony |
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| ES494769A0 (es) | 1979-09-05 | 1981-07-16 | Glaxo Group Ltd | Un procedimiento para la pre-paracion de fenoxialcoxifenil- derivados. |
| US4666928A (en) | 1984-08-30 | 1987-05-19 | Merck Frosst Canada, Ind. | Propylphenoxy pyridine carboxylates as leukotriene antagonists |
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| CN101048157A (zh) | 2004-10-25 | 2007-10-03 | 默克公司 | 代谢型谷氨酸受体的杂环二氢茚酮增强剂 |
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| KR20070106690A (ko) | 2004-12-27 | 2007-11-05 | 아스트라제네카 아베 | 피라졸론 화합물 및 대사성 글루타메이트 수용체길항제로서 그들의 용도 |
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-
2009
- 2009-07-10 TW TW098123468A patent/TW201006801A/zh unknown
- 2009-07-13 AR ARP090102635A patent/AR074631A1/es not_active Application Discontinuation
- 2009-07-14 WO PCT/US2009/050440 patent/WO2010009062A1/en not_active Ceased
- 2009-07-14 BR BRPI0915977A patent/BRPI0915977A2/pt not_active IP Right Cessation
- 2009-07-14 KR KR1020117001166A patent/KR101287713B1/ko not_active Expired - Fee Related
- 2009-07-14 JP JP2011518823A patent/JP5379227B2/ja not_active Expired - Fee Related
- 2009-07-14 US US12/502,252 patent/US7754742B2/en not_active Expired - Fee Related
- 2009-07-14 CN CN2009801274345A patent/CN102099344B/zh not_active Expired - Fee Related
- 2009-07-14 ES ES09790351T patent/ES2393243T3/es active Active
- 2009-07-14 EP EP09790351A patent/EP2318375B1/en active Active
- 2009-07-14 HR HRP20120830AT patent/HRP20120830T1/hr unknown
- 2009-07-14 PL PL09790351T patent/PL2318375T3/pl unknown
- 2009-07-14 DK DK09790351.2T patent/DK2318375T3/da active
- 2009-07-14 EA EA201170227A patent/EA018434B1/ru not_active IP Right Cessation
- 2009-07-14 CA CA2731215A patent/CA2731215C/en not_active Expired - Fee Related
- 2009-07-14 SI SI200930350T patent/SI2318375T1/sl unknown
- 2009-07-14 PT PT09790351T patent/PT2318375E/pt unknown
- 2009-07-14 MX MX2011000611A patent/MX2011000611A/es active IP Right Grant
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2012
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Also Published As
| Publication number | Publication date |
|---|---|
| JP5379227B2 (ja) | 2013-12-25 |
| MX2011000611A (es) | 2011-03-01 |
| CN102099344B (zh) | 2013-10-30 |
| KR101287713B1 (ko) | 2013-07-23 |
| CN102099344A (zh) | 2011-06-15 |
| CA2731215C (en) | 2013-08-27 |
| EP2318375B1 (en) | 2012-09-19 |
| SI2318375T1 (sl) | 2012-11-30 |
| TW201006801A (en) | 2010-02-16 |
| KR20110022676A (ko) | 2011-03-07 |
| EA018434B1 (ru) | 2013-07-30 |
| WO2010009062A1 (en) | 2010-01-21 |
| EP2318375A1 (en) | 2011-05-11 |
| ES2393243T3 (es) | 2012-12-19 |
| DK2318375T3 (da) | 2012-10-08 |
| CY1113315T1 (el) | 2016-04-13 |
| AU2009271105A1 (en) | 2010-01-21 |
| US7754742B2 (en) | 2010-07-13 |
| US20100016373A1 (en) | 2010-01-21 |
| HRP20120830T1 (hr) | 2012-11-30 |
| PL2318375T3 (pl) | 2013-02-28 |
| AR074631A1 (es) | 2011-02-02 |
| EA201170227A1 (ru) | 2011-06-30 |
| CA2731215A1 (en) | 2010-01-21 |
| JP2011528658A (ja) | 2011-11-24 |
| BRPI0915977A2 (pt) | 2018-10-30 |
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