MXPA04012439A - Amidas de acidos 2-heteroarilcarboxilicos. - Google Patents
Amidas de acidos 2-heteroarilcarboxilicos.Info
- Publication number
- MXPA04012439A MXPA04012439A MXPA04012439A MXPA04012439A MXPA04012439A MX PA04012439 A MXPA04012439 A MX PA04012439A MX PA04012439 A MXPA04012439 A MX PA04012439A MX PA04012439 A MXPA04012439 A MX PA04012439A MX PA04012439 A MXPA04012439 A MX PA04012439A
- Authority
- MX
- Mexico
- Prior art keywords
- mmol
- alkyl
- oct
- azabicyclo
- carboxamide
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 335
- -1 1-aza-bicyclo [2.2.2]oct-3-yl Chemical group 0.000 claims abstract description 257
- 239000002904 solvent Substances 0.000 claims abstract description 147
- 150000003839 salts Chemical class 0.000 claims abstract description 81
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 51
- 150000002367 halogens Chemical class 0.000 claims abstract description 51
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 44
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 33
- 125000003118 aryl group Chemical group 0.000 claims abstract description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 229910052717 sulfur Chemical group 0.000 claims abstract description 18
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001301 oxygen Substances 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000005605 benzo group Chemical group 0.000 claims abstract description 13
- 239000011593 sulfur Chemical group 0.000 claims abstract description 13
- 230000015654 memory Effects 0.000 claims abstract description 12
- 230000013016 learning Effects 0.000 claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
- 238000011321 prophylaxis Methods 0.000 claims abstract description 7
- 230000008447 perception Effects 0.000 claims abstract description 6
- 201000010099 disease Diseases 0.000 claims abstract description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 224
- 239000012453 solvate Substances 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 150000002431 hydrogen Chemical class 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 21
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 20
- 239000000460 chlorine Chemical group 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 239000011737 fluorine Chemical group 0.000 claims description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- 239000002585 base Substances 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000007513 acids Chemical class 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 125000000732 arylene group Chemical group 0.000 claims description 7
- 125000005549 heteroarylene group Chemical group 0.000 claims description 7
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 5
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims description 5
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 5
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 4
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 241001024304 Mino Species 0.000 claims 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 411
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 303
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 275
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 174
- 239000000243 solution Substances 0.000 description 152
- 239000000203 mixture Substances 0.000 description 139
- 239000012458 free base Substances 0.000 description 124
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 121
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 113
- 229910002666 PdCl2 Inorganic materials 0.000 description 111
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 105
- 239000000047 product Substances 0.000 description 100
- 238000001035 drying Methods 0.000 description 98
- 238000002953 preparative HPLC Methods 0.000 description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 95
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- 239000011541 reaction mixture Substances 0.000 description 81
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
- 239000012043 crude product Substances 0.000 description 66
- 238000000746 purification Methods 0.000 description 63
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 62
- 229910000029 sodium carbonate Inorganic materials 0.000 description 62
- 235000002639 sodium chloride Nutrition 0.000 description 62
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 235000017550 sodium carbonate Nutrition 0.000 description 59
- 235000011121 sodium hydroxide Nutrition 0.000 description 57
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 239000005909 Kieselgur Substances 0.000 description 50
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 46
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 46
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 39
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 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 30
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 29
- 239000003480 eluent Substances 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 238000012360 testing method Methods 0.000 description 27
- 238000001816 cooling Methods 0.000 description 25
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 23
- 235000011056 potassium acetate Nutrition 0.000 description 23
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 19
- JWCRXRGSXCXKPX-ZOWNYOTGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-bromo-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@H]1NC(=O)C1=CC(C=CC=C2Br)=C2O1 JWCRXRGSXCXKPX-ZOWNYOTGSA-N 0.000 description 18
- 238000004611 spectroscopical analysis Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- CSDWOMRGGUXKTK-ZOWNYOTGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-bromo-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@H]1NC(=O)C1=CC(C=CC=C2Br)=C2S1 CSDWOMRGGUXKTK-ZOWNYOTGSA-N 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 16
- 150000002500 ions Chemical class 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229910052796 boron Inorganic materials 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000002156 mixing Methods 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 14
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 235000019253 formic acid Nutrition 0.000 description 12
- 238000000926 separation method Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 11
- 208000002193 Pain Diseases 0.000 description 11
- HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-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
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 206010012289 Dementia Diseases 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 230000002378 acidificating effect Effects 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 230000003197 catalytic effect Effects 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- GRHBNDHCXARNLO-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-bromo-1-benzofuran-2-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC(Br)=CC=C2O1 GRHBNDHCXARNLO-ZDUSSCGKSA-N 0.000 description 9
- KXMRMWGSFCMYEJ-ZOWNYOTGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-bromo-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC=C(Br)C=C2S1 KXMRMWGSFCMYEJ-ZOWNYOTGSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 8
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- FKSLYSSVKFYJKE-UHFFFAOYSA-N n,n-diethylethanamine;methanol Chemical compound OC.CCN(CC)CC FKSLYSSVKFYJKE-UHFFFAOYSA-N 0.000 description 8
- OMJHFZCWUQSYEQ-CYBMUJFWSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-bromo-1-benzofuran-2-carboxamide Chemical compound C1N(CC2)CCC2[C@@H]1NC(=O)C1=CC(C=CC=C2Br)=C2O1 OMJHFZCWUQSYEQ-CYBMUJFWSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 235000011181 potassium carbonates Nutrition 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- WHDIUBHAKZDSJL-UHFFFAOYSA-N (4-morpholin-4-ylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1N1CCOCC1 WHDIUBHAKZDSJL-UHFFFAOYSA-N 0.000 description 6
- SBDOSRWGEWIYEP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2OC(C(=O)N)=CC2=C1 SBDOSRWGEWIYEP-UHFFFAOYSA-N 0.000 description 6
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- VQVGFSXPIRLHTJ-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-morpholin-4-ylphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.N([C@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C(C=C1)=CC=C1N1CCOCC1 VQVGFSXPIRLHTJ-GNAFDRTKSA-N 0.000 description 1
- DHOHZNJDTBESFH-HXUWFJFHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide Chemical compound OCC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@H]1C3CCN(CC3)C1)=C2 DHOHZNJDTBESFH-HXUWFJFHSA-N 0.000 description 1
- NZAWQLDJVDNGEG-GJFSDDNBSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(piperidine-1-carbonyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.N([C@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C(C=1)=CC=CC=1C(=O)N1CCCCC1 NZAWQLDJVDNGEG-GJFSDDNBSA-N 0.000 description 1
- KXNXPLFXTDYMHK-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(morpholine-4-carbonyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.N([C@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C(C=C1)=CC=C1C(=O)N1CCOCC1 KXNXPLFXTDYMHK-GNAFDRTKSA-N 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004718 n-hexylthio group Chemical group C(CCCCC)S* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000007996 neuronal plasticity Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- ZHVULPDNOFUIML-UHFFFAOYSA-N octane;hydrochloride Chemical compound Cl.CCCCCCCC ZHVULPDNOFUIML-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- DVCFNCQPOANJGU-UHFFFAOYSA-N oxolane-2-carbonyl chloride Chemical compound ClC(=O)C1CCCO1 DVCFNCQPOANJGU-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 125000004675 pentylcarbonyl group Chemical group C(CCCC)C(=O)* 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000004673 propylcarbonyl group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QKIPWYSRBGTXRG-UHFFFAOYSA-N tert-butyl 4-(4-bromophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(Br)C=C1 QKIPWYSRBGTXRG-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000000542 thalamic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10225536 | 2002-06-10 | ||
| DE10257078A DE10257078A1 (de) | 2002-12-06 | 2002-12-06 | 2-Heteroarylcarbonsäureamide |
| DE2002157537 DE10257537A1 (de) | 2002-12-10 | 2002-12-10 | 2-Heteroarylcarbonsäureamide |
| DE10305922A DE10305922A1 (de) | 2002-06-10 | 2003-02-13 | 2-Heteroarylcarbonsäureamide |
| PCT/EP2003/005735 WO2003104227A1 (de) | 2002-01-20 | 2003-06-02 | 2-heteroarylcarbonsäureamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA04012439A true MXPA04012439A (es) | 2005-04-19 |
Family
ID=29740887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA04012439A MXPA04012439A (es) | 2002-06-10 | 2003-06-02 | Amidas de acidos 2-heteroarilcarboxilicos. |
Country Status (16)
| Country | Link |
|---|---|
| US (5) | US7977485B2 (enExample) |
| EP (1) | EP1515967B1 (enExample) |
| JP (1) | JP4542891B2 (enExample) |
| CN (1) | CN1675204A (enExample) |
| AT (1) | ATE344262T1 (enExample) |
| AU (1) | AU2003238450A1 (enExample) |
| BR (1) | BR0312446A (enExample) |
| CA (1) | CA2488761C (enExample) |
| DE (1) | DE50305587D1 (enExample) |
| ES (1) | ES2276072T3 (enExample) |
| IL (1) | IL165505A0 (enExample) |
| MX (1) | MXPA04012439A (enExample) |
| NO (1) | NO20050063L (enExample) |
| PL (1) | PL374551A1 (enExample) |
| UY (1) | UY27841A1 (enExample) |
| WO (1) | WO2003104227A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| ATE344262T1 (de) * | 2002-06-10 | 2006-11-15 | Bayer Healthcare Ag | 2-heteroarylcarbonsäureamide |
| AU2003276919B2 (en) | 2002-09-25 | 2013-05-16 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
| DE602004031124D1 (de) | 2003-08-13 | 2011-03-03 | Neurosearch As | Neue chinuklidinderivative und deren pharmazeutische verwendung |
| WO2005063767A2 (en) | 2003-12-22 | 2005-07-14 | Memory Pharmaceuticals Corporation | Indoles, 1h-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof |
| US20050234095A1 (en) | 2004-03-25 | 2005-10-20 | Wenge Xie | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| US7514450B2 (en) | 2004-05-19 | 2009-04-07 | Neurosearch A/S | Azabicyclic aryl derivatives |
| CN100588657C (zh) | 2004-10-15 | 2010-02-10 | 神经研究公司 | 新的氮杂双环芳基衍生物及其医药用途 |
| US8106066B2 (en) * | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
| CN101910159B (zh) | 2007-12-26 | 2013-06-19 | 卫材R&D管理有限公司 | 杂环取代吡啶衍生物的制备方法 |
| US8367676B2 (en) * | 2009-06-30 | 2013-02-05 | Astrazeneca Ab | 2-carboxamide-7-piperazinyl-benzofuran derivatives 774 |
| JP5749797B2 (ja) | 2010-05-17 | 2015-07-15 | フォルム ファーマシューティカルズ、インコーポレイテッド | （ｒ）−７−クロロ−ｎ−（キヌクリジン−３−イル）ベンゾ［ｂ］チオフェン−２−カルボキサミド塩酸塩一水和物の結晶形 |
| KR20130132932A (ko) | 2010-12-20 | 2013-12-05 | 아스트라제네카 아베 | 2-카르복스아미드-4-피페라지닐-벤조푸란 유도체 |
| KR101928505B1 (ko) * | 2011-01-28 | 2018-12-12 | 에스케이바이오팜 주식회사 | 피리돈 유도체 및 이를 포함하는 약학적 조성물 |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| CN111205283A (zh) * | 2020-01-20 | 2020-05-29 | 广州九植医药科技有限公司 | 一种盐酸帕洛诺司琼有关物质b的合成方法 |
| CN111205284A (zh) * | 2020-01-20 | 2020-05-29 | 广州九植医药科技有限公司 | 一种盐酸帕洛诺司琼有关物质a的合成方法 |
| EP4213832A4 (en) * | 2020-09-18 | 2024-10-16 | Merck Sharp & Dohme LLC | Modified benzofuran-carboxamides as glucosylceramide synthase inhibitors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0000540D0 (sv) * | 2000-02-18 | 2000-02-18 | Astrazeneca Ab | New compounds |
| JP4616971B2 (ja) * | 2000-07-18 | 2011-01-19 | 田辺三菱製薬株式会社 | １−アザビシクロアルカン化合物およびその医薬用途 |
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| EA007429B1 (ru) | 2001-10-02 | 2006-10-27 | Фармация Энд Апджон Компани | Азабициклические замещённые конденсированные гетероарильные соединения |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| ATE344262T1 (de) * | 2002-06-10 | 2006-11-15 | Bayer Healthcare Ag | 2-heteroarylcarbonsäureamide |
| DE10234424A1 (de) | 2002-07-29 | 2004-02-12 | Bayer Ag | Benzothiophen-, Benzofuran- und Indolharnstoffe |
-
2003
- 2003-06-02 AT AT03732517T patent/ATE344262T1/de not_active IP Right Cessation
- 2003-06-02 AU AU2003238450A patent/AU2003238450A1/en not_active Abandoned
- 2003-06-02 CA CA2488761A patent/CA2488761C/en not_active Expired - Fee Related
- 2003-06-02 PL PL03374551A patent/PL374551A1/xx not_active Application Discontinuation
- 2003-06-02 MX MXPA04012439A patent/MXPA04012439A/es unknown
- 2003-06-02 CN CNA038188511A patent/CN1675204A/zh active Pending
- 2003-06-02 US US10/516,777 patent/US7977485B2/en not_active Expired - Fee Related
- 2003-06-02 BR BR0312446-0A patent/BR0312446A/pt not_active Application Discontinuation
- 2003-06-02 EP EP03732517A patent/EP1515967B1/de not_active Expired - Lifetime
- 2003-06-02 JP JP2004511297A patent/JP4542891B2/ja not_active Expired - Fee Related
- 2003-06-02 WO PCT/EP2003/005735 patent/WO2003104227A1/de not_active Ceased
- 2003-06-02 ES ES03732517T patent/ES2276072T3/es not_active Expired - Lifetime
- 2003-06-02 DE DE50305587T patent/DE50305587D1/de not_active Expired - Lifetime
- 2003-06-10 UY UY27841A patent/UY27841A1/es not_active Application Discontinuation
-
2004
- 2004-12-02 IL IL16550504A patent/IL165505A0/xx unknown
-
2005
- 2005-01-06 NO NO20050063A patent/NO20050063L/no not_active Application Discontinuation
-
2011
- 2011-07-11 US US13/179,957 patent/US20110263591A1/en not_active Abandoned
-
2012
- 2012-03-06 US US13/412,946 patent/US20120258964A1/en not_active Abandoned
-
2014
- 2014-04-25 US US14/261,616 patent/US9067931B2/en not_active Expired - Fee Related
-
2015
- 2015-06-08 US US14/733,804 patent/US10214524B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20060160877A1 (en) | 2006-07-20 |
| UY27841A1 (es) | 2003-12-31 |
| PL374551A1 (en) | 2005-10-31 |
| NO20050063L (no) | 2005-01-06 |
| US20120258964A1 (en) | 2012-10-11 |
| US7977485B2 (en) | 2011-07-12 |
| US10214524B2 (en) | 2019-02-26 |
| CA2488761C (en) | 2011-05-31 |
| WO2003104227A1 (de) | 2003-12-18 |
| EP1515967B1 (de) | 2006-11-02 |
| AU2003238450A1 (en) | 2003-12-22 |
| US20160122337A1 (en) | 2016-05-05 |
| BR0312446A (pt) | 2005-04-19 |
| CN1675204A (zh) | 2005-09-28 |
| JP4542891B2 (ja) | 2010-09-15 |
| IL165505A0 (en) | 2006-01-15 |
| US20140350008A1 (en) | 2014-11-27 |
| JP2005533052A (ja) | 2005-11-04 |
| DE50305587D1 (en) | 2006-12-14 |
| EP1515967A1 (de) | 2005-03-23 |
| US9067931B2 (en) | 2015-06-30 |
| ATE344262T1 (de) | 2006-11-15 |
| ES2276072T3 (es) | 2007-06-16 |
| CA2488761A1 (en) | 2003-12-18 |
| US20110263591A1 (en) | 2011-10-27 |
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