EA018434B1 - Имидазолкарбоксамиды - Google Patents
Имидазолкарбоксамиды Download PDFInfo
- Publication number
- EA018434B1 EA018434B1 EA201170227A EA201170227A EA018434B1 EA 018434 B1 EA018434 B1 EA 018434B1 EA 201170227 A EA201170227 A EA 201170227A EA 201170227 A EA201170227 A EA 201170227A EA 018434 B1 EA018434 B1 EA 018434B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- methyl
- mmol
- pharmaceutically acceptable
- hydroxy
- acceptable salt
- Prior art date
Links
- NMIZONYLXCOHEF-UHFFFAOYSA-N 1h-imidazole-2-carboxamide Chemical class NC(=O)C1=NC=CN1 NMIZONYLXCOHEF-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 184
- 150000003839 salts Chemical class 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 208000020401 Depressive disease Diseases 0.000 claims description 14
- 150000002431 hydrogen Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 229910052731 fluorine Chemical group 0.000 claims description 7
- 239000011737 fluorine Chemical group 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
- 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 description 5
- 125000001246 bromo group Chemical group Br* 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical group COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 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
- 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 230000008520 organization Effects 0.000 claims 1
- 238000001819 mass spectrum Methods 0.000 description 173
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 166
- -1 azidomethyl Chemical group 0.000 description 107
- 239000011541 reaction mixture Substances 0.000 description 73
- 238000003786 synthesis reaction Methods 0.000 description 73
- 230000015572 biosynthetic process Effects 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- 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
- 239000000203 mixture Substances 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 42
- 239000012044 organic layer Substances 0.000 description 40
- 239000000243 solution Substances 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 34
- 239000012458 free base Substances 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000012267 brine Substances 0.000 description 26
- 230000004044 response Effects 0.000 description 26
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 239000000126 substance Substances 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 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
- 108020003175 receptors Proteins 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- WZTRQGJMMHMFGH-UHFFFAOYSA-N 1-methyl-imidazole-4-carboxylic acid Chemical compound CN1C=NC(C(O)=O)=C1 WZTRQGJMMHMFGH-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 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 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
- 230000002787 reinforcement Effects 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 239000000047 product Substances 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
- 229910052740 iodine Inorganic materials 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 230000036760 body temperature Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-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
- 230000036506 anxiety Effects 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000036031 hyperthermia Effects 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 230000003389 potentiating effect 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
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 208000024891 symptom Diseases 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 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 208000029364 generalized anxiety disease Diseases 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
- 239000002244 precipitate Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000010926 purge Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- MWOGNXZJWMLRTF-UHFFFAOYSA-N 1-(2,4-dihydroxy-3-iodophenyl)-2-methylpropan-1-one Chemical compound CC(C)C(=O)C1=CC=C(O)C(I)=C1O MWOGNXZJWMLRTF-UHFFFAOYSA-N 0.000 description 3
- XMZKXYBXQCAUHQ-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-methylpropan-1-one Chemical compound CC(C)C(=O)C1=CC=C(O)C=C1O XMZKXYBXQCAUHQ-UHFFFAOYSA-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
- UQQHMXJCLHSYRV-UHFFFAOYSA-N 1-tritylimidazole-4-carboxylic acid Chemical compound C1=NC(C(=O)O)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UQQHMXJCLHSYRV-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
- 241000124008 Mammalia Species 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- 239000000556 agonist Substances 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
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- 230000000694 effects Effects 0.000 description 3
- 239000000284 extract Substances 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
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 208000024714 major depressive disease Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 102000006239 metabotropic receptors Human genes 0.000 description 3
- 108020004083 metabotropic receptors Proteins 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-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
- 239000000523 sample Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 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 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 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 2
- RFLAUWNOBFBDSR-UHFFFAOYSA-N 1-(2,4-dihydroxy-3-iodophenyl)-3-methylbutan-1-one Chemical compound CC(C)CC(=O)C1=CC=C(O)C(I)=C1O RFLAUWNOBFBDSR-UHFFFAOYSA-N 0.000 description 2
- AFLATBREDGLLKS-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-3-methylbutan-1-one Chemical compound CC(C)CC(=O)C1=CC=C(O)C=C1O AFLATBREDGLLKS-UHFFFAOYSA-N 0.000 description 2
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- CKIQYFBSBWCACB-UHFFFAOYSA-N cyclobutyl-[2,4-dihydroxy-3-(trifluoromethyl)phenyl]methanone Chemical compound OC1=C(C(F)(F)F)C(O)=CC=C1C(=O)C1CCC1 CKIQYFBSBWCACB-UHFFFAOYSA-N 0.000 description 1
- NZPBJLJEUCRVSU-UHFFFAOYSA-N cyclopentyl-(2,4-dihydroxyphenyl)methanone Chemical compound OC1=CC(O)=CC=C1C(=O)C1CCCC1 NZPBJLJEUCRVSU-UHFFFAOYSA-N 0.000 description 1
- GPVQBRRZDNFGDE-UHFFFAOYSA-N cyclopentyl-[2,4-dihydroxy-3-(trifluoromethyl)phenyl]methanone Chemical compound OC1=C(C(F)(F)F)C(O)=CC=C1C(=O)C1CCCC1 GPVQBRRZDNFGDE-UHFFFAOYSA-N 0.000 description 1
- SFZAZDNHIMVPIY-UHFFFAOYSA-N cyclopropyl-(2,4-dihydroxy-3-iodophenyl)methanone Chemical compound OC1=C(I)C(O)=CC=C1C(=O)C1CC1 SFZAZDNHIMVPIY-UHFFFAOYSA-N 0.000 description 1
- HFFJQBGUCYMTFY-UHFFFAOYSA-N cyclopropyl-(2,4-dihydroxyphenyl)methanone Chemical compound OC1=CC(O)=CC=C1C(=O)C1CC1 HFFJQBGUCYMTFY-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- SRLRUPFYGYMEIR-UHFFFAOYSA-N diazonio-[(3-methoxy-4-methoxycarbonylphenyl)methyl]azanide Chemical compound COC(=O)C1=CC=C(CN=[N+]=[N-])C=C1OC SRLRUPFYGYMEIR-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 239000000928 excitatory amino acid agonist Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- OXYWOYHZTYKFCT-UHFFFAOYSA-N fluorosulfonyl acetate Chemical compound CC(=O)OS(F)(=O)=O OXYWOYHZTYKFCT-UHFFFAOYSA-N 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001057 ionotropic effect Effects 0.000 description 1
- LVPMIMZXDYBCDF-UHFFFAOYSA-N isocinchomeronic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)N=C1 LVPMIMZXDYBCDF-UHFFFAOYSA-N 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 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
- 238000004895 liquid chromatography mass spectrometry Methods 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
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- FPISVJZHEXEKFZ-UHFFFAOYSA-N methyl 1-propan-2-ylimidazole-4-carboxylate Chemical compound COC(=O)C1=CN(C(C)C)C=N1 FPISVJZHEXEKFZ-UHFFFAOYSA-N 0.000 description 1
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-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
- YBEKNOSAAIRRRW-UHFFFAOYSA-N methyl 3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CNC(=O)OC(C)(C)C)=C1 YBEKNOSAAIRRRW-UHFFFAOYSA-N 0.000 description 1
- DFFXODHIBKZVSS-UHFFFAOYSA-N methyl 3-[[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN(C)C(=O)OC(C)(C)C)=C1 DFFXODHIBKZVSS-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
- IEPLSLWGRRQIPX-UHFFFAOYSA-N methyl 4-(aminomethyl)-2-chlorobenzoate Chemical compound COC(=O)C1=CC=C(CN)C=C1Cl IEPLSLWGRRQIPX-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
- 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
- LGEMXFQDNNYNGQ-UHFFFAOYSA-N methyl 4-(bromomethyl)-2-chlorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1Cl LGEMXFQDNNYNGQ-UHFFFAOYSA-N 0.000 description 1
- DCXFLSHDURQRML-UHFFFAOYSA-N methyl 4-(bromomethyl)-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1OC DCXFLSHDURQRML-UHFFFAOYSA-N 0.000 description 1
- BTSFXVSAECXZNJ-UHFFFAOYSA-N methyl 4-cyano-2-fluorobenzoate Chemical compound COC(=O)C1=CC=C(C#N)C=C1F BTSFXVSAECXZNJ-UHFFFAOYSA-N 0.000 description 1
- UDAQXROOFWMMQD-UHFFFAOYSA-N methyl 6-(azidomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CN=[N+]=[N-])N=C1 UDAQXROOFWMMQD-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- FEKRFYZGYUTGRY-UHFFFAOYSA-N n'-ethylmethanediimine Chemical compound CCN=C=N FEKRFYZGYUTGRY-UHFFFAOYSA-N 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
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- AOAKTDXVNCQZSB-UHFFFAOYSA-N n-[[4-[[3-hydroxy-4-(2-methylpropanoyl)-2-(trifluoromethyl)phenoxy]methyl]-2-methylphenyl]methyl]-1-methylimidazole-4-carboxamide Chemical compound FC(F)(F)C1=C(O)C(C(=O)C(C)C)=CC=C1OCC(C=C1C)=CC=C1CNC(=O)C1=CN(C)C=N1 AOAKTDXVNCQZSB-UHFFFAOYSA-N 0.000 description 1
- LDEYWJJVDZWHNP-UHFFFAOYSA-N n-[[4-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-(trifluoromethyl)phenoxy]methyl]-2-methylphenyl]methyl]-1-methylimidazole-4-carboxamide Chemical compound C=1C=C(CNC(=O)C=2N=CN(C)C=2)C(C)=CC=1COC1=CC=C(C(=O)CC(C)(C)C)C(O)=C1C(F)(F)F LDEYWJJVDZWHNP-UHFFFAOYSA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000012154 norepinephrine uptake Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- LJCNRYVRMXRIQR-UHFFFAOYSA-L potassium sodium tartrate Chemical compound [Na+].[K+].[O-]C(=O)C(O)C(O)C([O-])=O LJCNRYVRMXRIQR-UHFFFAOYSA-L 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 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
- 229960003770 reboxetine Drugs 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012549 training 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
- 238000005406 washing Methods 0.000 description 1
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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8177408P | 2008-07-18 | 2008-07-18 | |
| PCT/US2009/050440 WO2010009062A1 (en) | 2008-07-18 | 2009-07-14 | Imidazole carboxamides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201170227A1 EA201170227A1 (ru) | 2011-06-30 |
| EA018434B1 true EA018434B1 (ru) | 2013-07-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201170227A EA018434B1 (ru) | 2008-07-18 | 2009-07-14 | Имидазолкарбоксамиды |
Country Status (19)
| Country | Link |
|---|---|
| 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 |
| JP5547194B2 (ja) | 2008-09-02 | 2014-07-09 | ジャンセン ファーマシューティカルズ， インコーポレイテッド． | 代謝型グルタミン酸受容体の調節因子としての３−アザビシクロ［３．１．０］ヘキシル誘導体 |
| RU2517181C2 (ru) | 2008-10-16 | 2014-05-27 | Орто-Макнейл-Янссен Фармасьютикалз, Инк. | Производные индола и бензоморфолина в качестве модулятора метаботропных глутаматных рецепторов |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| CN102439008B (zh) | 2009-05-12 | 2015-04-29 | 杨森制药有限公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其用于治疗或预防神经和精神病症的用途 |
| MY153912A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 1, 2, 4,-triazolo[4,3-a[pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| CN103261195B (zh) | 2010-11-08 | 2015-09-02 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| PL2649069T3 (pl) | 2010-11-08 | 2016-01-29 | Janssen Pharmaceuticals Inc | Pochodne 1,2,4-triazolo[4,3-a]pirydyny i ich zastosowanie jako dodatnich allosterycznych modulatorów receptorów mGluR2 |
| CN103502218B (zh) * | 2011-03-04 | 2016-08-17 | 生命科技公司 | 用于缀合生物分子的化合物和方法 |
| EP2691393B1 (en) | 2011-03-31 | 2016-09-14 | Pfizer Inc | Novel bicyclic pyridinones |
| UA110688C2 (uk) | 2012-09-21 | 2016-01-25 | Пфайзер Інк. | Біциклічні піридинони |
| US20140206667A1 (en) | 2012-11-14 | 2014-07-24 | Michela Gallagher | Methods and compositions for treating schizophrenia |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| HUE053734T2 (hu) | 2014-01-21 | 2021-07-28 | Janssen Pharmaceutica Nv | 2-es altípusú metabotróp glutamáterg receptor pozitív allosztérikus modulátorait tartalmazó kombinációk és alkalmazásuk |
| KR20220049612A (ko) | 2014-01-21 | 2022-04-21 | 얀센 파마슈티카 엔.브이. | 대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도 |
| MX368391B (es) | 2015-02-03 | 2019-09-30 | Pfizer | Ciclopropabenzofuranil-piridopirazindionas novedosas. |
| CN107207449B (zh) * | 2015-04-23 | 2020-11-10 | 豪夫迈·罗氏有限公司 | 用于治疗精神障碍的四唑衍生物 |
| CN104788694B (zh) * | 2015-04-29 | 2018-06-08 | 江苏亚宝绝缘材料股份有限公司 | 一种超低收缩率的聚酰亚胺薄膜 |
| CN108137566B (zh) | 2015-10-06 | 2021-05-25 | 豪夫迈·罗氏有限公司 | 三唑衍生物 |
| EP3411365B1 (en) | 2016-02-02 | 2019-11-20 | H. Hoffnabb-La Roche Ag | Pyrazol-pyridine derivatives as eaat3 inhibitors |
| EP3464246B1 (en) | 2016-05-27 | 2020-07-08 | H. Hoffnabb-La Roche Ag | Pyrazol compounds as eaat3 inhibitors |
| CN109563049B (zh) | 2016-10-14 | 2022-11-29 | 豪夫迈·罗氏有限公司 | 作为eaat3抑制剂的咪唑化合物 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006014918A2 (en) * | 2004-07-30 | 2006-02-09 | Merck & Co., Inc. | Heterocyclic acetophenone potentiators of metabotropic glutamate receptors |
| WO2006057860A1 (en) * | 2004-11-22 | 2006-06-01 | Eli Lilly And Company | Potentiators of glutamate receptors |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DE69210091T2 (de) | 1991-05-31 | 1996-10-02 | Sumitomo Pharma | Leukotrien-B4-Antagonisten |
| WO2001056990A2 (en) | 2000-02-03 | 2001-08-09 | Eli Lilly And Company | Pyridine derivates as potentiators of glutamate receptors |
| JP2006502143A (ja) * | 2002-08-26 | 2006-01-19 | メルク エンド カムパニー インコーポレーテッド | 向代謝型グルタミン酸受容体のアセトフェノン増強因子 |
| EP1773792A1 (en) | 2004-07-30 | 2007-04-18 | Merck & Co., Inc. | Indanone potentiators of metabotropic glutamate receptors |
| TW200613272A (en) | 2004-08-13 | 2006-05-01 | Astrazeneca Ab | Isoindolone compounds and their use as metabotropic glutamate receptor potentiators |
| 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 |
| KR20070106690A (ko) | 2004-12-27 | 2007-11-05 | 아스트라제네카 아베 | 피라졸론 화합물 및 대사성 글루타메이트 수용체길항제로서 그들의 용도 |
| CN101309905A (zh) | 2005-08-12 | 2008-11-19 | 阿斯利康(瑞典)有限公司 | 取代的异吲哚酮及其作为代谢型谷氨酸受体增效剂的用途 |
-
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
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006014918A2 (en) * | 2004-07-30 | 2006-02-09 | Merck & Co., Inc. | Heterocyclic acetophenone potentiators of metabotropic glutamate receptors |
| WO2006057860A1 (en) * | 2004-11-22 | 2006-06-01 | Eli Lilly And Company | Potentiators of glutamate receptors |
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 |
| 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 |
| PT2318375E (pt) | 2012-10-22 |
| 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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