AU2003238450A1 - 2-heteroaryl carboxamides - Google Patents
2-heteroaryl carboxamides Download PDFInfo
- Publication number
- AU2003238450A1 AU2003238450A1 AU2003238450A AU2003238450A AU2003238450A1 AU 2003238450 A1 AU2003238450 A1 AU 2003238450A1 AU 2003238450 A AU2003238450 A AU 2003238450A AU 2003238450 A AU2003238450 A AU 2003238450A AU 2003238450 A1 AU2003238450 A1 AU 2003238450A1
- Authority
- AU
- Australia
- Prior art keywords
- mmol
- oct
- azabicyclo
- alkyl
- salts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 230000013016 learning Effects 0.000 claims abstract description 11
- 230000015654 memory Effects 0.000 claims abstract description 10
- 239000003814 drug Substances 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 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 331
- 238000000034 method Methods 0.000 claims description 231
- -1 1-azabicyclo[2.2.2]oct-3-yl Chemical group 0.000 claims description 212
- 239000000203 mixture Substances 0.000 claims description 162
- 239000002904 solvent Substances 0.000 claims description 147
- 150000003839 salts Chemical class 0.000 claims description 82
- 239000012453 solvate Substances 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 56
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 150000002431 hydrogen Chemical class 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 27
- 239000000460 chlorine Substances 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 239000005864 Sulphur Substances 0.000 claims description 12
- 125000005605 benzo group Chemical group 0.000 claims description 12
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 9
- 230000008569 process Effects 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
- 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 7
- 125000005549 heteroarylene group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- WXLPFZKLJWNZSL-UHFFFAOYSA-N [N].C1CC2CCN1CC2 Chemical group [N].C1CC2CCN1CC2 WXLPFZKLJWNZSL-UHFFFAOYSA-N 0.000 claims description 4
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 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 3
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 519
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 305
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 216
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 195
- 238000004128 high performance liquid chromatography Methods 0.000 description 178
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 176
- 239000000243 solution Substances 0.000 description 169
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 156
- 239000012458 free base Substances 0.000 description 128
- 238000005160 1H NMR spectroscopy Methods 0.000 description 127
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 119
- 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
- 238000001035 drying Methods 0.000 description 101
- 239000000047 product Substances 0.000 description 101
- 101150003085 Pdcl gene Proteins 0.000 description 97
- 238000002953 preparative HPLC Methods 0.000 description 95
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- 239000011541 reaction mixture Substances 0.000 description 83
- 238000007429 general method Methods 0.000 description 79
- 238000000746 purification Methods 0.000 description 67
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
- 239000012043 crude product Substances 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 65
- 229910000029 sodium carbonate Inorganic materials 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- 235000017550 sodium carbonate Nutrition 0.000 description 58
- 235000011121 sodium hydroxide Nutrition 0.000 description 58
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 48
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 29
- 238000001816 cooling Methods 0.000 description 29
- 239000003480 eluent Substances 0.000 description 29
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
- 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 27
- 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 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- 235000011056 potassium acetate Nutrition 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 23
- 238000012360 testing method Methods 0.000 description 22
- 238000010438 heat treatment Methods 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 21
- 150000003254 radicals Chemical class 0.000 description 21
- BVYUKLDJKTVDRA-FYZYNONXSA-N 3-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzofuran-7-yl]benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 BVYUKLDJKTVDRA-FYZYNONXSA-N 0.000 description 20
- 238000001914 filtration Methods 0.000 description 19
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
- 239000007821 HATU Substances 0.000 description 18
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 17
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 17
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
- 238000004611 spectroscopical analysis Methods 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 150000002500 ions Chemical class 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- VZGVVSVVVHCQOR-FYZYNONXSA-N 3-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 VZGVVSVVVHCQOR-FYZYNONXSA-N 0.000 description 15
- 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
- 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
- 229910021529 ammonia Inorganic materials 0.000 description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 14
- 229940087646 methanolamine Drugs 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- YYSWMYSFKQPZMS-FYZYNONXSA-N 7-(3-aminophenyl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.NC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 YYSWMYSFKQPZMS-FYZYNONXSA-N 0.000 description 13
- 101100028920 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cfp gene Proteins 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 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 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- UVKVGWAZQWEEQA-IBGZPJMESA-N 7-(3-aminophenyl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 UVKVGWAZQWEEQA-IBGZPJMESA-N 0.000 description 12
- 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
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 12
- 235000019253 formic acid Nutrition 0.000 description 12
- 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 12
- 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 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229960001866 silicon dioxide Drugs 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
- 125000005842 heteroatom Chemical group 0.000 description 11
- STZHBULOYDCZET-KLXURFKVSA-N (3r)-1-azabicyclo[2.2.2]octan-3-amine;dihydrochloride Chemical compound Cl.Cl.C1CC2[C@@H](N)CN1CC2 STZHBULOYDCZET-KLXURFKVSA-N 0.000 description 10
- 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 10
- 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 235000011054 acetic acid Nutrition 0.000 description 10
- 150000003857 carboxamides Chemical class 0.000 description 10
- 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 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 9
- 230000003197 catalytic effect Effects 0.000 description 9
- NTMXUUXGPAUABI-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-bromo-1-benzofuran-2-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC=C(Br)C=C2O1 NTMXUUXGPAUABI-ZDUSSCGKSA-N 0.000 description 9
- OMJHFZCWUQSYEQ-ZDUSSCGKSA-N n-[(3r)-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-ZDUSSCGKSA-N 0.000 description 9
- CSDWOMRGGUXKTK-BTQNPOSSSA-N n-[(3s)-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-BTQNPOSSSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- WHDIUBHAKZDSJL-UHFFFAOYSA-N (4-morpholin-4-ylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1N1CCOCC1 WHDIUBHAKZDSJL-UHFFFAOYSA-N 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 8
- 206010012289 Dementia Diseases 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 239000003054 catalyst Substances 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
- 239000012071 phase Substances 0.000 description 8
- 229920001467 poly(styrenesulfonates) Polymers 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
- QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 7
- SIBGLSZEOSPDIJ-IBGZPJMESA-N 7-(2-aminophenyl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound NC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 SIBGLSZEOSPDIJ-IBGZPJMESA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 7
- XLTANAWLDBYGFU-VTLKBQQISA-N methyllycaconitine Chemical compound C([C@]12CN([C@@H]3[C@@]4(O)[C@]5(O)[C@H]6[C@@H](OC)[C@@H]([C@H](C5)OC)C[C@H]6[C@@]3([C@@H]1[C@@H]4OC)[C@@H](OC)CC2)CC)OC(=O)C1=CC=CC=C1N1C(=O)C[C@H](C)C1=O XLTANAWLDBYGFU-VTLKBQQISA-N 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- GGWMDIVPQQRETL-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 GGWMDIVPQQRETL-FYZYNONXSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
- FHIPWWBGMKCJOZ-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2SC(C(=O)N)=CC2=C1 FHIPWWBGMKCJOZ-UHFFFAOYSA-N 0.000 description 6
- BVYUKLDJKTVDRA-FSRHSHDFSA-N 3-[2-[[(3s)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzofuran-7-yl]benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 BVYUKLDJKTVDRA-FSRHSHDFSA-N 0.000 description 6
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 6
- OPYANDYWSZSRSD-UHFFFAOYSA-N 7-bromo-1-benzofuran-2-carboxylic acid Chemical compound C1=CC(Br)=C2OC(C(=O)O)=CC2=C1 OPYANDYWSZSRSD-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- AFHOBSCDNXGFMO-UHFFFAOYSA-N [2-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=CC=C1B(O)O AFHOBSCDNXGFMO-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- RXHKXPZVNJCVKS-GXKRWWSZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[(e)-n'-hydroxycarbamimidoyl]-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC=C(C(=NO)N)C=C2S1 RXHKXPZVNJCVKS-GXKRWWSZSA-N 0.000 description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000000825 ultraviolet detection Methods 0.000 description 6
- DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical class C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 5
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 4
- IBTSWKLSEOGJGJ-UHFFFAOYSA-N (3-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=CC(B(O)O)=C1 IBTSWKLSEOGJGJ-UHFFFAOYSA-N 0.000 description 4
- FXNQUGGIXKWAJA-UHFFFAOYSA-N (3-morpholin-4-ylphenyl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC(N2CCOCC2)=C1 FXNQUGGIXKWAJA-UHFFFAOYSA-N 0.000 description 4
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 4
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- WGSHXXURTKJFMP-UHFFFAOYSA-N [4-(morpholine-4-carbonyl)phenyl] trifluoromethanesulfonate Chemical compound C1=CC(OS(=O)(=O)C(F)(F)F)=CC=C1C(=O)N1CCOCC1 WGSHXXURTKJFMP-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- 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 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 3
- MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 3
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 3
- KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 description 3
- DBVFWZMQJQMJCB-UHFFFAOYSA-N 3-boronobenzoic acid Chemical compound OB(O)C1=CC=CC(C(O)=O)=C1 DBVFWZMQJQMJCB-UHFFFAOYSA-N 0.000 description 3
- UDLGTTKXEYIEMM-UHFFFAOYSA-N 3-bromo-1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2C(Br)=C(C(=O)O)SC2=C1 UDLGTTKXEYIEMM-UHFFFAOYSA-N 0.000 description 3
- SOYBEXQHNURCGE-UHFFFAOYSA-N 3-ethoxypropan-1-amine Chemical compound CCOCCCN SOYBEXQHNURCGE-UHFFFAOYSA-N 0.000 description 3
- FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical compound COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 description 3
- SZMBYXUOLCRIIL-UHFFFAOYSA-N 4-(4-bromophenyl)morpholin-3-one Chemical compound C1=CC(Br)=CC=C1N1C(=O)COCC1 SZMBYXUOLCRIIL-UHFFFAOYSA-N 0.000 description 3
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 3
- 208000008035 Back Pain Diseases 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 208000000094 Chronic Pain Diseases 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- HGTDLKXUWVKLQX-UHFFFAOYSA-N [3-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=CC(B(O)O)=C1 HGTDLKXUWVKLQX-UHFFFAOYSA-N 0.000 description 3
- RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 3
- PZRPBPMLSSNFOM-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=C(B(O)O)C=C1 PZRPBPMLSSNFOM-UHFFFAOYSA-N 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 230000000366 juvenile effect Effects 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- DFNZFCPEUDSNEO-UHFFFAOYSA-N tert-butyl n-[(2-bromophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC=C1Br DFNZFCPEUDSNEO-UHFFFAOYSA-N 0.000 description 3
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- WQPLCWXXJWECGD-UHFFFAOYSA-N (2-morpholin-4-ylphenyl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC=C1N1CCOCC1 WQPLCWXXJWECGD-UHFFFAOYSA-N 0.000 description 2
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 2
- STZHBULOYDCZET-XCUBXKJBSA-N (3s)-1-azabicyclo[2.2.2]octan-3-amine;dihydrochloride Chemical compound Cl.Cl.C1CC2[C@H](N)CN1CC2 STZHBULOYDCZET-XCUBXKJBSA-N 0.000 description 2
- DCNMATSPQKWETQ-UHFFFAOYSA-N (5-acetylthiophen-2-yl)boronic acid Chemical compound CC(=O)C1=CC=C(B(O)O)S1 DCNMATSPQKWETQ-UHFFFAOYSA-N 0.000 description 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 2
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 2
- NASLINFISOTVJJ-UHFFFAOYSA-N 1,2-oxazole-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=NO1 NASLINFISOTVJJ-UHFFFAOYSA-N 0.000 description 2
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
- SKCNYQBWULWGAP-UHFFFAOYSA-N 1-(3-bromophenyl)pyrrolidine Chemical compound BrC1=CC=CC(N2CCCC2)=C1 SKCNYQBWULWGAP-UHFFFAOYSA-N 0.000 description 2
- YINFEFUSAQRZGG-UHFFFAOYSA-N 1-(4-bromophenyl)pyrrolidin-2-one Chemical compound C1=CC(Br)=CC=C1N1C(=O)CCC1 YINFEFUSAQRZGG-UHFFFAOYSA-N 0.000 description 2
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical class C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 2
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 2
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 2
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- STBGLXMINLWCNL-UHFFFAOYSA-N 3-bromo-2-hydroxybenzaldehyde Chemical compound OC1=C(Br)C=CC=C1C=O STBGLXMINLWCNL-UHFFFAOYSA-N 0.000 description 2
- UJTKZWNRUPTHSB-UHFFFAOYSA-N 4-(4-bromophenyl)morpholine Chemical compound C1=CC(Br)=CC=C1N1CCOCC1 UJTKZWNRUPTHSB-UHFFFAOYSA-N 0.000 description 2
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
- ONNFNEFYXIPHCA-UHFFFAOYSA-N 5-bromo-1-benzothiophene-2-carboxylic acid Chemical compound BrC1=CC=C2SC(C(=O)O)=CC2=C1 ONNFNEFYXIPHCA-UHFFFAOYSA-N 0.000 description 2
- ULBSHNJYWRMJRZ-UHFFFAOYSA-N 6-bromo-1-benzofuran-2-carboxylic acid Chemical compound C1=C(Br)C=C2OC(C(=O)O)=CC2=C1 ULBSHNJYWRMJRZ-UHFFFAOYSA-N 0.000 description 2
- PTCGELMNYHRYFV-UHFFFAOYSA-N 6-cyano-1-benzothiophene-2-carboxylic acid Chemical compound C1=C(C#N)C=C2SC(C(=O)O)=CC2=C1 PTCGELMNYHRYFV-UHFFFAOYSA-N 0.000 description 2
- KUHIBBPVHSFXGO-UHFFFAOYSA-N 7-(2-methoxyphenyl)-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=CC=C1C1=CC=CC2=C1OC(C(O)=O)=C2 KUHIBBPVHSFXGO-UHFFFAOYSA-N 0.000 description 2
- WOMIRHBFYRQSAJ-FJSYBICCSA-N 7-[2-(aminomethyl)phenyl]-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.NCC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 WOMIRHBFYRQSAJ-FJSYBICCSA-N 0.000 description 2
- MNDJMYUMAYIZFS-FJSYBICCSA-N 7-[2-(aminomethyl)phenyl]-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.NCC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 MNDJMYUMAYIZFS-FJSYBICCSA-N 0.000 description 2
- WOMIRHBFYRQSAJ-FAVHNTAZSA-N 7-[2-(aminomethyl)phenyl]-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.NCC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@H]1C3CCN(CC3)C1)=C2 WOMIRHBFYRQSAJ-FAVHNTAZSA-N 0.000 description 2
- YYKIKWNYRWUIKB-UHFFFAOYSA-N 7-bromo-1-benzothiophene-2-carboxylic acid Chemical compound C1=CC(Br)=C2SC(C(=O)O)=CC2=C1 YYKIKWNYRWUIKB-UHFFFAOYSA-N 0.000 description 2
- IZWDHPQCEFISNF-UHFFFAOYSA-N 7-bromo-5-fluoro-1-benzofuran-2-carboxylic acid Chemical compound FC1=CC(Br)=C2OC(C(=O)O)=CC2=C1 IZWDHPQCEFISNF-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 206010013496 Disturbance in attention Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 208000008930 Low Back Pain Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- HUOFUOCSQCYFPW-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(OC(F)(F)F)C=C1 HUOFUOCSQCYFPW-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N anhydrous diethylene glycol Natural products OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 125000006309 butyl amino group Chemical group 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229950005499 carbon tetrachloride Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229940125810 compound 20 Drugs 0.000 description 2
- WEPUZBYKXNKSDH-UHFFFAOYSA-N cyclopentanecarbonyl chloride Chemical compound ClC(=O)C1CCCC1 WEPUZBYKXNKSDH-UHFFFAOYSA-N 0.000 description 2
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000005826 halohydrocarbons Chemical class 0.000 description 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- KRRAZMUPVIGDCU-UHFFFAOYSA-N methyl 1-benzothiophene-2-carboxylate Chemical class C1=CC=C2SC(C(=O)OC)=CC2=C1 KRRAZMUPVIGDCU-UHFFFAOYSA-N 0.000 description 2
- XDYVZHUZZZKQOS-UHFFFAOYSA-N methyl 5-bromo-1-benzothiophene-2-carboxylate Chemical compound BrC1=CC=C2SC(C(=O)OC)=CC2=C1 XDYVZHUZZZKQOS-UHFFFAOYSA-N 0.000 description 2
- SFDVDNLBYGHFNF-UHFFFAOYSA-N methyl 6-bromo-1-benzothiophene-2-carboxylate Chemical compound C1=C(Br)C=C2SC(C(=O)OC)=CC2=C1 SFDVDNLBYGHFNF-UHFFFAOYSA-N 0.000 description 2
- BXZLWSCTNQNCPB-UHFFFAOYSA-N methyl 6-cyano-1-benzothiophene-2-carboxylate Chemical compound C1=C(C#N)C=C2SC(C(=O)OC)=CC2=C1 BXZLWSCTNQNCPB-UHFFFAOYSA-N 0.000 description 2
- 229940095102 methyl benzoate Drugs 0.000 description 2
- 229940073584 methylene chloride Drugs 0.000 description 2
- FRZAEBZEHFXWKR-UHFFFAOYSA-N methyllycaconitine Natural products CCN1CC2(COC(=O)c3ccccc3N4C(=O)CC(C)C4=O)CCC(O)C56C7CC8C(O)C7C(O)(CC8OC)C(O)(C(OC)C25)C16 FRZAEBZEHFXWKR-UHFFFAOYSA-N 0.000 description 2
- XLTANAWLDBYGFU-UHFFFAOYSA-N methyllycaconitine hydrochloride Natural products C1CC(OC)C2(C3C4OC)C5CC(C(C6)OC)C(OC)C5C6(O)C4(O)C2N(CC)CC31COC(=O)C1=CC=CC=C1N1C(=O)CC(C)C1=O XLTANAWLDBYGFU-UHFFFAOYSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- XWOAOKQHDOCPIG-ZOWNYOTGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-bromo-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC(Br)=CC=C2S1 XWOAOKQHDOCPIG-ZOWNYOTGSA-N 0.000 description 2
- MQXVJFYRXWZXAI-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-formylphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(C=O)=CC=C1C1=CC=C(C=C(S2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 MQXVJFYRXWZXAI-BDQAORGHSA-N 0.000 description 2
- KKJJEXUJVQOYHW-UQKRIMTDSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-cyano-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1=C(C#N)C=C2SC(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC2=C1 KKJJEXUJVQOYHW-UQKRIMTDSA-N 0.000 description 2
- JHWISQRMMDVQNX-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.OCC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 JHWISQRMMDVQNX-BDQAORGHSA-N 0.000 description 2
- KYJLJVCNRRBZOH-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-bromo-5-fluoro-1-benzofuran-2-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC(F)=CC(Br)=C2O1 KYJLJVCNRRBZOH-ZDUSSCGKSA-N 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- BEBHRWCMWLGUCJ-UHFFFAOYSA-N thiophene-2-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1=CC=CS1 BEBHRWCMWLGUCJ-UHFFFAOYSA-N 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- CMMXCVYESRODNH-UHFFFAOYSA-N trichloroepoxyethane Chemical class ClC1OC1(Cl)Cl CMMXCVYESRODNH-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- QOZLFNQLIKOGDR-UHFFFAOYSA-N (2,5-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(OC)C(B(O)O)=C1 QOZLFNQLIKOGDR-UHFFFAOYSA-N 0.000 description 1
- UKTAURVTSWDIQR-UHFFFAOYSA-N (3-aminophenyl)boronic acid;sulfuric acid Chemical compound OS(O)(=O)=O.NC1=CC=CC(B(O)O)=C1.NC1=CC=CC(B(O)O)=C1 UKTAURVTSWDIQR-UHFFFAOYSA-N 0.000 description 1
- HJBGZJMKTOMQRR-UHFFFAOYSA-N (3-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=O)=C1 HJBGZJMKTOMQRR-UHFFFAOYSA-N 0.000 description 1
- JKXVWJCIIFBENM-UHFFFAOYSA-N (3-piperidin-1-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(N2CCCCC2)=C1 JKXVWJCIIFBENM-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- GJHYHTYGGHFYNN-UHFFFAOYSA-N (4-hydroxyphenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(O)=CC=C1C(=O)N1CCOCC1 GJHYHTYGGHFYNN-UHFFFAOYSA-N 0.000 description 1
- YUTPAZKVEOJQCY-UHFFFAOYSA-N (4-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=NC=C1B(O)O YUTPAZKVEOJQCY-UHFFFAOYSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- LEUXOIBRUWVBGM-UHFFFAOYSA-N 1-(3-bromophenyl)pyrrole Chemical compound BrC1=CC=CC(N2C=CC=C2)=C1 LEUXOIBRUWVBGM-UHFFFAOYSA-N 0.000 description 1
- BVEGBJXZICCEQW-UHFFFAOYSA-N 1-(4-bromophenyl)pyrrolidine Chemical compound C1=CC(Br)=CC=C1N1CCCC1 BVEGBJXZICCEQW-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- REUAXQZIRFXQML-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-amine Chemical compound C1CC2C(N)CN1CC2 REUAXQZIRFXQML-UHFFFAOYSA-N 0.000 description 1
- KHAKFKRESWHJHB-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-amine;hydrochloride Chemical compound Cl.C1CC2C(N)CN1CC2 KHAKFKRESWHJHB-UHFFFAOYSA-N 0.000 description 1
- DYEHDACATJUKSZ-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octane;bromide Chemical compound [Br-].C1CC2CC[NH+]1CC2 DYEHDACATJUKSZ-UHFFFAOYSA-N 0.000 description 1
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- PBBBVRMFQSDGTP-UHFFFAOYSA-N 1h-quinolin-2-ylidenemethanone Chemical compound C1=CC=C2C=CC(=C=O)NC2=C1 PBBBVRMFQSDGTP-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- ZCJRWQDZPIIYLM-UHFFFAOYSA-N 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC=C1N ZCJRWQDZPIIYLM-UHFFFAOYSA-N 0.000 description 1
- LIALQTZNSARKNP-UHFFFAOYSA-N 2-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CCN=C=NC(C)CN(C)C LIALQTZNSARKNP-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- MLONYBFKXHEPCD-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO MLONYBFKXHEPCD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MEYRABVEYCFHHB-UHFFFAOYSA-N 2-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Br MEYRABVEYCFHHB-UHFFFAOYSA-N 0.000 description 1
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- VMPYFWTYGZZUMY-UHFFFAOYSA-N 2-morpholin-4-ylphenol Chemical compound OC1=CC=CC=C1N1CCOCC1 VMPYFWTYGZZUMY-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- MPSXGPCFLAGJOM-UHFFFAOYSA-M 2-tert-butyl-5-methyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1=CC=[N+](C(C)(C)C)O1 MPSXGPCFLAGJOM-UHFFFAOYSA-M 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- XWEZXLNRMJJYKB-IBGZPJMESA-N 3-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 XWEZXLNRMJJYKB-IBGZPJMESA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
- AWUMBCKNGJAKOM-UHFFFAOYSA-N 3-amino-1-benzothiophene-2-carboxylic acid Chemical class C1=CC=C2C(N)=C(C(O)=O)SC2=C1 AWUMBCKNGJAKOM-UHFFFAOYSA-N 0.000 description 1
- OUAZPCKRSSEQKB-UHFFFAOYSA-N 3-bromo-2-fluorobenzaldehyde Chemical compound FC1=C(Br)C=CC=C1C=O OUAZPCKRSSEQKB-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- BMGSGGYIUOQZBZ-UHFFFAOYSA-N 3-morpholin-4-ylphenol Chemical compound OC1=CC=CC(N2CCOCC2)=C1 BMGSGGYIUOQZBZ-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- SGUXGSGHYOGBDH-UHFFFAOYSA-N 4-(2-bromophenyl)morpholine Chemical compound BrC1=CC=CC=C1N1CCOCC1 SGUXGSGHYOGBDH-UHFFFAOYSA-N 0.000 description 1
- FAICPWQABJYYLF-FYZYNONXSA-N 4-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzofuran-7-yl]benzoic acid;hydrochloride Chemical compound Cl.C1=CC(C(=O)O)=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 FAICPWQABJYYLF-FYZYNONXSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- LAYNZUFIYSYHIV-UHFFFAOYSA-N 4-bromo-1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1Br LAYNZUFIYSYHIV-UHFFFAOYSA-N 0.000 description 1
- UPCARQPLANFGQJ-UHFFFAOYSA-N 4-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC(Br)=CC=C1C=O UPCARQPLANFGQJ-UHFFFAOYSA-N 0.000 description 1
- HXTWKHXDFATMSP-UHFFFAOYSA-N 4-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC(Br)=CC=C1C=O HXTWKHXDFATMSP-UHFFFAOYSA-N 0.000 description 1
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
- KNKVNTDAQHBEAW-UHFFFAOYSA-N 4-formyl-3-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC(C#N)=CC=C1C=O KNKVNTDAQHBEAW-UHFFFAOYSA-N 0.000 description 1
- FHQRDEDZJIFJAL-UHFFFAOYSA-N 4-phenylmorpholine Chemical compound C1COCCN1C1=CC=CC=C1 FHQRDEDZJIFJAL-UHFFFAOYSA-N 0.000 description 1
- WSRGGSAGSUEJKQ-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=CN=C1 WSRGGSAGSUEJKQ-UHFFFAOYSA-N 0.000 description 1
- QKUWZCOVKRUXKX-UHFFFAOYSA-N 5-bromo-1-benzofuran-2-carboxylic acid Chemical compound BrC1=CC=C2OC(C(=O)O)=CC2=C1 QKUWZCOVKRUXKX-UHFFFAOYSA-N 0.000 description 1
- MMFGGDVQLQQQRX-UHFFFAOYSA-N 5-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C=C1C=O MMFGGDVQLQQQRX-UHFFFAOYSA-N 0.000 description 1
- SFPGNDANMWJZEN-UHFFFAOYSA-N 6-(4-bromophenyl)piperidin-2-one Chemical compound C1=CC(Br)=CC=C1C1NC(=O)CCC1 SFPGNDANMWJZEN-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- CKBBSFOOIOHLPC-UHFFFAOYSA-N 6-bromo-1-benzothiophene-2-carboxylic acid Chemical compound C1=C(Br)C=C2SC(C(=O)O)=CC2=C1 CKBBSFOOIOHLPC-UHFFFAOYSA-N 0.000 description 1
- SXAKEWUEIOCXEV-IAXIZFETSA-N 7-(2-methoxyphenyl)-n-[(3r)-1-oxido-1-azoniabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CC[N+](CC3)([O-])C1)=C2 SXAKEWUEIOCXEV-IAXIZFETSA-N 0.000 description 1
- UDOCDIRMIYYLOB-BOXHHOBZSA-N 7-(3-acetamidophenyl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 UDOCDIRMIYYLOB-BOXHHOBZSA-N 0.000 description 1
- UDOCDIRMIYYLOB-ZMBIFBSDSA-N 7-(3-acetamidophenyl)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 UDOCDIRMIYYLOB-ZMBIFBSDSA-N 0.000 description 1
- KLCDWRDHDCFWNP-UHFFFAOYSA-N 7-(4-morpholin-4-ylphenyl)-1-benzothiophene-2-carboxylic acid Chemical compound C=12SC(C(=O)O)=CC2=CC=CC=1C(C=C1)=CC=C1N1CCOCC1 KLCDWRDHDCFWNP-UHFFFAOYSA-N 0.000 description 1
- BNLHHFZQAXVKEK-LMOVPXPDSA-N 7-(5-acetylthiophen-2-yl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.S1C(C(=O)C)=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 BNLHHFZQAXVKEK-LMOVPXPDSA-N 0.000 description 1
- ZJXLBJPXKJOKNV-LMOVPXPDSA-N 7-(5-acetylthiophen-2-yl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.S1C(C(=O)C)=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 ZJXLBJPXKJOKNV-LMOVPXPDSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- CSPZDOVYNLEOMR-RFVHGSKJSA-N Cl.N12C[C@H](C(CC1)CC2)C2=C(SC1=C2C=CC=C1Br)C(=O)N Chemical compound Cl.N12C[C@H](C(CC1)CC2)C2=C(SC1=C2C=CC=C1Br)C(=O)N CSPZDOVYNLEOMR-RFVHGSKJSA-N 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- XJZSCIADJSDAIV-FTBISJDPSA-N [2-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]phenyl]methyl n-ethylcarbamate;hydrochloride Chemical compound Cl.CCNC(=O)OCC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 XJZSCIADJSDAIV-FTBISJDPSA-N 0.000 description 1
- XBWQNXGLLASYCC-BOXHHOBZSA-N [2-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]phenyl]methyl n-methylcarbamate;hydrochloride Chemical compound Cl.CNC(=O)OCC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 XBWQNXGLLASYCC-BOXHHOBZSA-N 0.000 description 1
- UWDFWVLAHRQSKK-UHFFFAOYSA-N [3-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(OC(F)(F)F)=C1 UWDFWVLAHRQSKK-UHFFFAOYSA-N 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- NEAFVIGRLGRBAB-FYZYNONXSA-N acetic acid;n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzofuran-2-carboxamide Chemical compound CC(O)=O.COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 NEAFVIGRLGRBAB-FYZYNONXSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 208000019804 backache Diseases 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 125000006251 butylcarbonyl group Chemical group 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 208000022371 chronic pain syndrome Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- 229960002887 deanol Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- IGSSNLHDFIYOIL-UHFFFAOYSA-N furan-2-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1=CC=CO1 IGSSNLHDFIYOIL-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 239000004312 hexamethylene tetramine Substances 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- 125000004871 hexylcarbonyl group Chemical group C(CCCCC)C(=O)* 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000006328 iso-butylcarbonyl group Chemical group [H]C([H])([H])C([H])(C(*)=O)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000028252 learning or memory Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- GWAOCMULROPWPS-UHFFFAOYSA-N methyl 7-(4-morpholin-4-ylphenyl)-1-benzothiophene-2-carboxylate Chemical compound C=12SC(C(=O)OC)=CC2=CC=CC=1C(C=C1)=CC=C1N1CCOCC1 GWAOCMULROPWPS-UHFFFAOYSA-N 0.000 description 1
- JEHZRZXWHVICJQ-UHFFFAOYSA-N methyl 7-bromo-1-benzothiophene-2-carboxylate Chemical compound C1=CC(Br)=C2SC(C(=O)OC)=CC2=C1 JEHZRZXWHVICJQ-UHFFFAOYSA-N 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- JKRHDMPWBFBQDZ-UHFFFAOYSA-N n'-hexylmethanediimine Chemical compound CCCCCCN=C=N JKRHDMPWBFBQDZ-UHFFFAOYSA-N 0.000 description 1
- CSDWOMRGGUXKTK-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-7-bromo-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2C1NC(=O)C1=CC(C=CC=C2Br)=C2S1 CSDWOMRGGUXKTK-UHFFFAOYSA-N 0.000 description 1
- LIJYXDKEMCTTAV-UHFFFAOYSA-N n-(3-bromophenyl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC(Br)=C1 LIJYXDKEMCTTAV-UHFFFAOYSA-N 0.000 description 1
- JRLDZDJDIKSMTP-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC2=C1 JRLDZDJDIKSMTP-ZDUSSCGKSA-N 0.000 description 1
- RPGSBNZLXGYEKO-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-(3-methoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=C3C=C(OC3=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 RPGSBNZLXGYEKO-BDQAORGHSA-N 0.000 description 1
- FEYMFOUQQMUELV-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-(4-methoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=C(OC(=C2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 FEYMFOUQQMUELV-BDQAORGHSA-N 0.000 description 1
- RXMHJWNJWYSNCK-NRFANRHFSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-[4-(dimethylamino)phenyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(OC(=C2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 RXMHJWNJWYSNCK-NRFANRHFSA-N 0.000 description 1
- UFEJUOHNLUOPIF-FQEVSTJZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-[4-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(CO)=CC=C1C1=CC=C(OC(=C2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 UFEJUOHNLUOPIF-FQEVSTJZSA-N 0.000 description 1
- KPVMQUJHIISKGL-ZOWNYOTGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-bromo-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC(Br)=CC=C2O1 KPVMQUJHIISKGL-ZOWNYOTGSA-N 0.000 description 1
- CHNNZNDVGNIBEB-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-fluoro-7-(4-fluorophenyl)-1-benzofuran-2-carboxamide Chemical compound C1=CC(F)=CC=C1C1=CC(F)=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 CHNNZNDVGNIBEB-IBGZPJMESA-N 0.000 description 1
- AZRZXPYNZJVMDQ-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-fluoro-7-[4-(trifluoromethoxy)phenyl]-1-benzofuran-2-carboxamide Chemical compound C=12OC(C(=O)N[C@@H]3C4CCN(CC4)C3)=CC2=CC(F)=CC=1C1=CC=C(OC(F)(F)F)C=C1 AZRZXPYNZJVMDQ-IBGZPJMESA-N 0.000 description 1
- BOYCRXDKBSPERF-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-phenyl-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=CC=2)=CC1=CC=2C1=CC=CC=C1 BOYCRXDKBSPERF-FYZYNONXSA-N 0.000 description 1
- LBQLTMAXUSYZKK-LMOVPXPDSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-pyrimidin-5-yl-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(OC1=CC=2)=CC1=CC=2C1=CN=CN=C1 LBQLTMAXUSYZKK-LMOVPXPDSA-N 0.000 description 1
- FGHDVXYYCDBAFO-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-formylphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.O=CC1=CC=CC(C=2C=C3SC(=CC3=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 FGHDVXYYCDBAFO-BDQAORGHSA-N 0.000 description 1
- ZDHIFKIDPBIPPW-INIZCTEOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-hydroxyprop-1-ynyl)-1-benzofuran-2-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC=C(C#CCO)C=C2O1 ZDHIFKIDPBIPPW-INIZCTEOSA-N 0.000 description 1
- VDZOZSIMSNEDBY-INIZCTEOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-hydroxyprop-1-ynyl)-1-benzothiophene-2-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=CC2=CC=C(C#CCO)C=C2S1 VDZOZSIMSNEDBY-INIZCTEOSA-N 0.000 description 1
- VVYFGHNZDYRXRI-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(3-methoxyphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=C3SC(=CC3=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 VVYFGHNZDYRXRI-BDQAORGHSA-N 0.000 description 1
- XDWQZQIWGVTRTI-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-fluorophenyl)-1-benzofuran-2-carboxamide Chemical compound C1=CC(F)=CC=C1C1=CC=C(C=C(O2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 XDWQZQIWGVTRTI-IBGZPJMESA-N 0.000 description 1
- YNMJIGUDTCTTHO-FQEVSTJZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-methoxyphenyl)-1-benzofuran-2-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C=C(O2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 YNMJIGUDTCTTHO-FQEVSTJZSA-N 0.000 description 1
- PFMCNPVNIZGPAY-QHCPKHFHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-morpholin-4-ylphenyl)-1-benzofuran-2-carboxamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(OC1=C2)=CC1=CC=C2C(C=C1)=CC=C1N1CCOCC1 PFMCNPVNIZGPAY-QHCPKHFHSA-N 0.000 description 1
- ZAVFLRDPMNSGPW-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(4-morpholin-4-ylphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=C2)=CC1=CC=C2C(C=C1)=CC=C1N1CCOCC1 ZAVFLRDPMNSGPW-BQAIUKQQSA-N 0.000 description 1
- PMTCGDOKLIKVHF-RSAXXLAASA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-(5-methyl-1,2,4-oxadiazol-3-yl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.O1C(C)=NC(C=2C=C3SC(=CC3=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=N1 PMTCGDOKLIKVHF-RSAXXLAASA-N 0.000 description 1
- GEVDLXSDEVMRLS-FQEVSTJZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[2-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide Chemical compound OCC1=CC=CC=C1C1=CC=C(C=C(O2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 GEVDLXSDEVMRLS-FQEVSTJZSA-N 0.000 description 1
- DNWAPYMKRABKSE-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[2-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.OCC1=CC=CC=C1C1=CC=C(C=C(S2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 DNWAPYMKRABKSE-BDQAORGHSA-N 0.000 description 1
- KMQBVTHMASPRAA-FQEVSTJZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[3-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide Chemical compound OCC1=CC=CC(C=2C=C3OC(=CC3=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 KMQBVTHMASPRAA-FQEVSTJZSA-N 0.000 description 1
- BQIKNBOYMQMZDE-ASMAMLKCSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[3-(morpholin-4-ylmethyl)phenyl]-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=C2)=CC1=CC=C2C(C=1)=CC=CC=1CN1CCOCC1 BQIKNBOYMQMZDE-ASMAMLKCSA-N 0.000 description 1
- XVTVUSYKOFWVTB-FQEVSTJZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[4-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(CO)=CC=C1C1=CC=C(C=C(O2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 XVTVUSYKOFWVTB-FQEVSTJZSA-N 0.000 description 1
- MTLZWDFZDOFDBK-ASMAMLKCSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[4-(morpholin-4-ylmethyl)phenyl]-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=C2)=CC1=CC=C2C(C=C1)=CC=C1CN1CCOCC1 MTLZWDFZDOFDBK-ASMAMLKCSA-N 0.000 description 1
- IQDSWXURZMFZKF-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-[4-(trifluoromethoxy)phenyl]-1-benzofuran-2-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(C=C(O2)C(=O)N[C@@H]3C4CCN(CC4)C3)C2=C1 IQDSWXURZMFZKF-IBGZPJMESA-N 0.000 description 1
- WASYXBGARLFHSX-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-6-phenyl-1-benzothiophene-2-carboxamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=C2)=CC1=CC=C2C1=CC=CC=C1 WASYXBGARLFHSX-IBGZPJMESA-N 0.000 description 1
- PSPIUJWJEVFDDH-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2,5-dimethoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 PSPIUJWJEVFDDH-BDQAORGHSA-N 0.000 description 1
- AULKCNUFUPZRCK-SFHVURJKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-hydroxyphenyl)-1-benzofuran-2-carboxamide Chemical compound OC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 AULKCNUFUPZRCK-SFHVURJKSA-N 0.000 description 1
- GUUAJKBOCMZUJW-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzofuran-2-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 GUUAJKBOCMZUJW-IBGZPJMESA-N 0.000 description 1
- CSAZWGWDFFIKDS-UTOQZODRSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzofuran-2-carboxamide;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 CSAZWGWDFFIKDS-UTOQZODRSA-N 0.000 description 1
- QCKKKAHWUBUBML-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzofuran-2-carboxamide;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 QCKKKAHWUBUBML-FYZYNONXSA-N 0.000 description 1
- LPIKUFDOSAFHCV-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzofuran-2-carboxamide;oxalic acid Chemical compound OC(=O)C(O)=O.COC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 LPIKUFDOSAFHCV-FYZYNONXSA-N 0.000 description 1
- QWGGANSVBBSVLS-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 QWGGANSVBBSVLS-FYZYNONXSA-N 0.000 description 1
- RRUSDGCJDDYNKV-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-morpholin-4-ylphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C1=CC=CC=C1N1CCOCC1 RRUSDGCJDDYNKV-FTBISJDPSA-N 0.000 description 1
- PTANFUHXXBXNJD-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-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=2C1=CC=CC=C1N1CCOCC1 PTANFUHXXBXNJD-FTBISJDPSA-N 0.000 description 1
- YBWWPQLXTGSLEJ-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-methoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 YBWWPQLXTGSLEJ-BDQAORGHSA-N 0.000 description 1
- JRUROZRRJHDYIP-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-methoxyphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 JRUROZRRJHDYIP-BDQAORGHSA-N 0.000 description 1
- GILITAGDTCAGEC-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-morpholin-4-ylphenyl)-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=1N1CCOCC1 GILITAGDTCAGEC-BQAIUKQQSA-N 0.000 description 1
- VEQDEPHGTYSSBX-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-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=1)=CC=CC=1N1CCOCC1 VEQDEPHGTYSSBX-BQAIUKQQSA-N 0.000 description 1
- OOKYCCUYJUVKQY-ASMAMLKCSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-piperidin-1-ylphenyl)-1-benzofuran-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C(C=1)=CC=CC=1N1CCCCC1 OOKYCCUYJUVKQY-ASMAMLKCSA-N 0.000 description 1
- WMQAXBPDNWDIAT-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-pyrrolidin-1-ylphenyl)-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=1N1CCCC1 WMQAXBPDNWDIAT-BQAIUKQQSA-N 0.000 description 1
- MNNRRGIOLLLBDZ-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-pyrrolidin-1-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=1)=CC=CC=1N1CCCC1 MNNRRGIOLLLBDZ-BQAIUKQQSA-N 0.000 description 1
- FMCSVMYTDGOSFW-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-methoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 FMCSVMYTDGOSFW-BDQAORGHSA-N 0.000 description 1
- SFXWDUQQWCCHMJ-FERBBOLQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-methoxypyridin-3-yl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=NC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 SFXWDUQQWCCHMJ-FERBBOLQSA-N 0.000 description 1
- UXZWHBDXIHZGPY-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-morpholin-4-ylphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C(C=C1)=CC=C1N1CCOCC1 UXZWHBDXIHZGPY-BQAIUKQQSA-N 0.000 description 1
- JEEDRXZYYQURBJ-IFUPQEAVSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-piperazin-1-ylphenyl)-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C(C=C1)=CC=C1N1CCNCC1 JEEDRXZYYQURBJ-IFUPQEAVSA-N 0.000 description 1
- YYBOSAHFOHEJFD-IFUPQEAVSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-pyrrolidin-1-ylphenyl)-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C(C=C1)=CC=C1N1CCCC1 YYBOSAHFOHEJFD-IFUPQEAVSA-N 0.000 description 1
- RULFMYJGMPXNON-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-(cyclobutanecarbonylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC=C(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)C=1NC(=O)C1CCC1 RULFMYJGMPXNON-BQAIUKQQSA-N 0.000 description 1
- FAAWEYGJDQWJBZ-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-(ethylcarbamoylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CCNC(=O)NC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 FAAWEYGJDQWJBZ-BOXHHOBZSA-N 0.000 description 1
- VPDLWAPCYGDQSH-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.OCC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 VPDLWAPCYGDQSH-BDQAORGHSA-N 0.000 description 1
- HNDHLQMCEPDYKU-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-(propan-2-ylcarbamoylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)NC(=O)NC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 HNDHLQMCEPDYKU-FTBISJDPSA-N 0.000 description 1
- IKSNOXFXVLTGJH-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-[(2-methoxyacetyl)amino]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COCC(=O)NC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 IKSNOXFXVLTGJH-BOXHHOBZSA-N 0.000 description 1
- DPPMJAJTWZWWBT-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-[(methylcarbamoylamino)methyl]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CNC(=O)NCC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 DPPMJAJTWZWWBT-BOXHHOBZSA-N 0.000 description 1
- RLGNNWRAYZFPIZ-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-[(methylcarbamoylamino)methyl]phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.CNC(=O)NCC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 RLGNNWRAYZFPIZ-BOXHHOBZSA-N 0.000 description 1
- NGZLVZLQFRXUKS-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(2,2-dimethylpropanoylamino)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)(C)C(=O)NC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 NGZLVZLQFRXUKS-FTBISJDPSA-N 0.000 description 1
- KPCPIGJYUKZWAM-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(2-methylpropanoylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)C(=O)NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 KPCPIGJYUKZWAM-FTBISJDPSA-N 0.000 description 1
- XZDAYHJEICUNSL-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(2-methylpropylcarbamoyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)CNC(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 XZDAYHJEICUNSL-BQAIUKQQSA-N 0.000 description 1
- VGAARBLRMOMEAD-JIDHJSLPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(3-ethoxypropylcarbamoyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.CCOCCCNC(=O)C1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 VGAARBLRMOMEAD-JIDHJSLPSA-N 0.000 description 1
- URLGVVDSLMSPML-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(3-methoxypropylcarbamoyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COCCCNC(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 URLGVVDSLMSPML-BQAIUKQQSA-N 0.000 description 1
- CQTKWZYWTQSQGA-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(3-methoxypropylcarbamoyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COCCCNC(=O)C1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 CQTKWZYWTQSQGA-BQAIUKQQSA-N 0.000 description 1
- QYTQGBMLQDJXPS-ASMAMLKCSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(4-methylpiperazine-1-carbonyl)phenyl]-1-benzofuran-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 QYTQGBMLQDJXPS-ASMAMLKCSA-N 0.000 description 1
- MKWFYTIDPCPAGM-ASMAMLKCSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(4-methylpiperazine-1-carbonyl)phenyl]-1-benzothiophene-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C(=O)C1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 MKWFYTIDPCPAGM-ASMAMLKCSA-N 0.000 description 1
- ACSMKOODFZIJDP-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(cyclobutanecarbonylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=CC=1NC(=O)C1CCC1 ACSMKOODFZIJDP-BQAIUKQQSA-N 0.000 description 1
- BTBGGJXFBDRXHG-JIDHJSLPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(cyclopentanecarbonylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=CC=1NC(=O)C1CCCC1 BTBGGJXFBDRXHG-JIDHJSLPSA-N 0.000 description 1
- BOBSKHDTCNZPRE-JIDHJSLPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(cyclopentanecarbonylamino)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=CC=1NC(=O)C1CCCC1 BOBSKHDTCNZPRE-JIDHJSLPSA-N 0.000 description 1
- MPIBSWXKPBIYSY-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(cyclopropanecarbonylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=CC=1NC(=O)C1CC1 MPIBSWXKPBIYSY-FTBISJDPSA-N 0.000 description 1
- AXWUBRGTWLIONY-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(cyclopropylcarbamoyl)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)NC1CC1 AXWUBRGTWLIONY-FTBISJDPSA-N 0.000 description 1
- PJRQXFGWPCLKOK-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(cyclopropylcarbamoyl)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=1)=CC=CC=1C(=O)NC1CC1 PJRQXFGWPCLKOK-FTBISJDPSA-N 0.000 description 1
- KXXZIZSSAZZGCD-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(ethylcarbamoylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CCNC(=O)NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 KXXZIZSSAZZGCD-BOXHHOBZSA-N 0.000 description 1
- ZETSMJQVULWERM-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(furan-2-carbonylamino)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=1NC(=O)C1=CC=CO1 ZETSMJQVULWERM-FTBISJDPSA-N 0.000 description 1
- YIIRHVZCNHETFZ-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(hydroxymethyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.OCC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 YIIRHVZCNHETFZ-BDQAORGHSA-N 0.000 description 1
- DCRJXEQUQPIBRH-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.OCC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 DCRJXEQUQPIBRH-BDQAORGHSA-N 0.000 description 1
- IGBWREDAHGJHLG-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(methanesulfonamido)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CS(=O)(=O)NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 IGBWREDAHGJHLG-BDQAORGHSA-N 0.000 description 1
- BUGAZEVYWQMRHV-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(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=1)=CC=CC=1C(=O)N1CCOCC1 BUGAZEVYWQMRHV-BQAIUKQQSA-N 0.000 description 1
- NZAWQLDJVDNGEG-JIDHJSLPSA-N n-[(3r)-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-JIDHJSLPSA-N 0.000 description 1
- KAAUMICKZHJLGK-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(propan-2-ylcarbamoylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)NC(=O)NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 KAAUMICKZHJLGK-FTBISJDPSA-N 0.000 description 1
- OJCVNGSYAMOWFW-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(tert-butylcarbamoylamino)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)(C)NC(=O)NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 OJCVNGSYAMOWFW-FTBISJDPSA-N 0.000 description 1
- RMLFSSUWADQBFL-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(trifluoromethoxy)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.FC(F)(F)OC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 RMLFSSUWADQBFL-FYZYNONXSA-N 0.000 description 1
- FXFDFVSZGLMPKA-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[(2-methoxyacetyl)amino]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COCC(=O)NC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 FXFDFVSZGLMPKA-BOXHHOBZSA-N 0.000 description 1
- JZZGTWVIDNGWED-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[(2-methoxyacetyl)amino]phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COCC(=O)NC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 JZZGTWVIDNGWED-BOXHHOBZSA-N 0.000 description 1
- IQLVDIUWRNJMOS-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[2-methoxyethyl(methyl)carbamoyl]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COCCN(C)C(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 IQLVDIUWRNJMOS-BQAIUKQQSA-N 0.000 description 1
- BDAZXZLNMPTPKT-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[ethyl(methyl)carbamoyl]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CCN(C)C(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 BDAZXZLNMPTPKT-FTBISJDPSA-N 0.000 description 1
- JNLZMZQMSGDAAS-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[ethyl(methyl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.CCN(C)C(=O)C1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 JNLZMZQMSGDAAS-FTBISJDPSA-N 0.000 description 1
- UWJKYUUDBJCIDO-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(2-oxopyrrolidin-1-yl)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=C1)=CC=C1N1CCCC1=O UWJKYUUDBJCIDO-FTBISJDPSA-N 0.000 description 1
- ZRKKJQQHZXQEOT-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(2-oxopyrrolidin-1-yl)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=C1N1CCCC1=O ZRKKJQQHZXQEOT-FTBISJDPSA-N 0.000 description 1
- JDZFIDNSGNVXOD-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(3-oxomorpholin-4-yl)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=C1)=CC=C1N1CCOCC1=O JDZFIDNSGNVXOD-FTBISJDPSA-N 0.000 description 1
- ZIELOMLFWGWTQE-FTBISJDPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(3-oxomorpholin-4-yl)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=C1N1CCOCC1=O ZIELOMLFWGWTQE-FTBISJDPSA-N 0.000 description 1
- CGAOXAKMQFLHAY-AEELKVOVSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(6-oxopiperidin-2-yl)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=C1C1CCCC(=O)N1 CGAOXAKMQFLHAY-AEELKVOVSA-N 0.000 description 1
- RIRRHIYGUMCLIQ-BOXHHOBZSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(dimethylamino)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(N(C)C)=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 RIRRHIYGUMCLIQ-BOXHHOBZSA-N 0.000 description 1
- SIWFTQZLIJOYLI-BDQAORGHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(CO)=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@@H]1C3CCN(CC3)C1)=C2 SIWFTQZLIJOYLI-BDQAORGHSA-N 0.000 description 1
- QUSFSLBLDWXAJB-BQAIUKQQSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-[4-(morpholine-4-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=C1)=CC=C1C(=O)N1CCOCC1 QUSFSLBLDWXAJB-BQAIUKQQSA-N 0.000 description 1
- KXNXPLFXTDYMHK-BQAIUKQQSA-N n-[(3r)-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-BQAIUKQQSA-N 0.000 description 1
- RVSVRSLGRHEPOS-FYZYNONXSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-phenyl-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C1=CC=CC=C1 RVSVRSLGRHEPOS-FYZYNONXSA-N 0.000 description 1
- GKEPFZSWIVOEHT-NTEVMMBTSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-pyridin-3-yl-1-benzofuran-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C1=CC=CN=C1 GKEPFZSWIVOEHT-NTEVMMBTSA-N 0.000 description 1
- AVUYWYZCWRSDBY-NTISSMGPSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-thiophen-2-yl-1-benzothiophene-2-carboxamide;formic acid Chemical compound OC=O.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C1=CC=CS1 AVUYWYZCWRSDBY-NTISSMGPSA-N 0.000 description 1
- QWGGANSVBBSVLS-FSRHSHDFSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-(2-methoxyphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C1=CC=CC2=C1SC(C(=O)N[C@H]1C3CCN(CC3)C1)=C2 QWGGANSVBBSVLS-FSRHSHDFSA-N 0.000 description 1
- YBWWPQLXTGSLEJ-VEIFNGETSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-methoxyphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 YBWWPQLXTGSLEJ-VEIFNGETSA-N 0.000 description 1
- JRUROZRRJHDYIP-VEIFNGETSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-methoxyphenyl)-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 JRUROZRRJHDYIP-VEIFNGETSA-N 0.000 description 1
- VEQDEPHGTYSSBX-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-(3-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=1)=CC=CC=1N1CCOCC1 VEQDEPHGTYSSBX-GNAFDRTKSA-N 0.000 description 1
- UXZWHBDXIHZGPY-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-(4-morpholin-4-ylphenyl)-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.N([C@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C(C=C1)=CC=C1N1CCOCC1 UXZWHBDXIHZGPY-GNAFDRTKSA-N 0.000 description 1
- 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
- DPPMJAJTWZWWBT-ZMBIFBSDSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[2-[(methylcarbamoylamino)methyl]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CNC(=O)NCC1=CC=CC=C1C1=CC=CC2=C1OC(C(=O)N[C@H]1C3CCN(CC3)C1)=C2 DPPMJAJTWZWWBT-ZMBIFBSDSA-N 0.000 description 1
- XZDAYHJEICUNSL-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(2-methylpropylcarbamoyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CC(C)CNC(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 XZDAYHJEICUNSL-GNAFDRTKSA-N 0.000 description 1
- URLGVVDSLMSPML-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(3-methoxypropylcarbamoyl)phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COCCCNC(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 URLGVVDSLMSPML-GNAFDRTKSA-N 0.000 description 1
- QYTQGBMLQDJXPS-PPLJNSMQSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-(4-methylpiperazine-1-carbonyl)phenyl]-1-benzofuran-2-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 QYTQGBMLQDJXPS-PPLJNSMQSA-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
- IQLVDIUWRNJMOS-GNAFDRTKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[2-methoxyethyl(methyl)carbamoyl]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.COCCN(C)C(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 IQLVDIUWRNJMOS-GNAFDRTKSA-N 0.000 description 1
- BDAZXZLNMPTPKT-VZYDHVRKSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-[3-[ethyl(methyl)carbamoyl]phenyl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.CCN(C)C(=O)C1=CC=CC(C=2C=3OC(=CC=3C=CC=2)C(=O)N[C@H]2C3CCN(CC3)C2)=C1 BDAZXZLNMPTPKT-VZYDHVRKSA-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
- KQCHXQVLPKWATJ-GMUIIQOCSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-7-pyridin-3-yl-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.N([C@H]1C2CCN(CC2)C1)C(=O)C(OC1=2)=CC1=CC=CC=2C1=CC=CN=C1 KQCHXQVLPKWATJ-GMUIIQOCSA-N 0.000 description 1
- NQACNYGRQKZOSU-BOXHHOBZSA-N n-[3-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]phenyl]-1,2-oxazole-5-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C(C=1)=CC=CC=1NC(=O)C1=CC=NO1 NQACNYGRQKZOSU-BOXHHOBZSA-N 0.000 description 1
- GNVOTYFUWPQXDQ-FTBISJDPSA-N n-[3-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]phenyl]furan-2-carboxamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)C(SC1=2)=CC1=CC=CC=2C(C=1)=CC=CC=1NC(=O)C1=CC=CO1 GNVOTYFUWPQXDQ-FTBISJDPSA-N 0.000 description 1
- DYLLWOUYHWQYSV-OSMMWLIYSA-N n-[3-[2-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamoyl]-1-benzothiophen-7-yl]phenyl]oxolane-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=3SC(=CC=3C=CC=2)C(=O)N[C@@H]2C3CCN(CC3)C2)=CC=1NC(=O)C1CCCO1 DYLLWOUYHWQYSV-OSMMWLIYSA-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
- 230000008764 nerve damage Effects 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
- 230000007996 neuronal plasticity Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 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
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 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
- 230000020477 pH reduction Effects 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
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 208000021090 palsy Diseases 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
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 125000004675 pentylcarbonyl group Chemical group C(CCCC)C(=O)* 0.000 description 1
- 210000000578 peripheral nerve Anatomy 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
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 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
- 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
- 239000013557 residual solvent Substances 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 239000000377 silicon dioxide 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
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 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
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 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
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10225536 | 2002-06-10 | ||
| DE10225536.9 | 2002-06-10 | ||
| DE10257078A DE10257078A1 (de) | 2002-12-06 | 2002-12-06 | 2-Heteroarylcarbonsäureamide |
| DE10257078.7 | 2002-12-06 | ||
| DE2002157537 DE10257537A1 (de) | 2002-12-10 | 2002-12-10 | 2-Heteroarylcarbonsäureamide |
| DE10257537.1 | 2002-12-10 | ||
| DE10305922A DE10305922A1 (de) | 2002-06-10 | 2003-02-13 | 2-Heteroarylcarbonsäureamide |
| DE10305922.9 | 2003-02-13 | ||
| PCT/EP2003/005735 WO2003104227A1 (de) | 2002-01-20 | 2003-06-02 | 2-heteroarylcarbonsäureamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2003238450A1 true AU2003238450A1 (en) | 2003-12-22 |
Family
ID=29740887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003238450A Abandoned AU2003238450A1 (en) | 2002-06-10 | 2003-06-02 | 2-heteroaryl carboxamides |
Country Status (16)
| Country | Link |
|---|---|
| US (5) | US7977485B2 (https=) |
| EP (1) | EP1515967B1 (https=) |
| JP (1) | JP4542891B2 (https=) |
| CN (1) | CN1675204A (https=) |
| AT (1) | ATE344262T1 (https=) |
| AU (1) | AU2003238450A1 (https=) |
| BR (1) | BR0312446A (https=) |
| CA (1) | CA2488761C (https=) |
| DE (1) | DE50305587D1 (https=) |
| ES (1) | ES2276072T3 (https=) |
| IL (1) | IL165505A0 (https=) |
| MX (1) | MXPA04012439A (https=) |
| NO (1) | NO20050063L (https=) |
| PL (1) | PL374551A1 (https=) |
| UY (1) | UY27841A1 (https=) |
| WO (1) | WO2003104227A1 (https=) |
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 |
| CN1675204A (zh) * | 2002-06-10 | 2005-09-28 | 拜耳医药保健股份公司 | 2－杂芳基甲酰胺 |
| MXPA05003317A (es) | 2002-09-25 | 2005-07-05 | Memory Pharm Corp | Indazoles, benzotiazoles y benzoisotiazoles asi como preparacion y usos de los mismos. |
| DE602004031124D1 (de) | 2003-08-13 | 2011-03-03 | Neurosearch As | Neue chinuklidinderivative und deren pharmazeutische verwendung |
| DE602004010299T2 (de) | 2003-12-22 | 2008-09-18 | Memory Pharmaceuticals Corp. | Indole, 1h-indazole, 1,2-benzisoxazole und 1,2-benzisothiazole und deren herstellung und anwendungen |
| NZ550534A (en) * | 2004-03-25 | 2009-07-31 | Memory Pharm Corp | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| JP2007538046A (ja) | 2004-05-19 | 2007-12-27 | ノイロサーチ アクティーゼルスカブ | 新規なアザビシクロアリール誘導体 |
| EP1802616B1 (en) | 2004-10-15 | 2011-01-12 | NeuroSearch A/S | Novel azabicyclic aryl derivatives and their medical use |
| US8106066B2 (en) | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
| US8410277B2 (en) | 2007-12-26 | 2013-04-02 | Eisai R&D Managment Co., Ltd. | Method for manufacturing heterocycle substituted pyridine derivatives |
| US8367676B2 (en) * | 2009-06-30 | 2013-02-05 | Astrazeneca Ab | 2-carboxamide-7-piperazinyl-benzofuran derivatives 774 |
| AR081402A1 (es) | 2010-05-17 | 2012-08-29 | Envivo Pharmaceuticals Inc | Una forma cristalina de clorhidrato de (r)-7-cloro-n-(quinuclidin-3-il) benzo(b)tiofeno-2-carboxamida monohidrato |
| CA2821480A1 (en) | 2010-12-20 | 2012-06-28 | Astrazeneca Ab | 2-carboxamide-4-piperazinyl-benzofuran derivative |
| 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 |
| 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 |
| 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 |
| 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 |
| HUP0402289A2 (hu) * | 2001-10-02 | 2005-02-28 | Pharmacia & Upjohn Company | Gyógyhatású azabiciklusos csoporttal helyettesített kondenzált heteroaril-származékok, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk |
| DE10164139A1 (de) * | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| CN1675204A (zh) * | 2002-06-10 | 2005-09-28 | 拜耳医药保健股份公司 | 2－杂芳基甲酰胺 |
| DE10234424A1 (de) | 2002-07-29 | 2004-02-12 | Bayer Ag | Benzothiophen-, Benzofuran- und Indolharnstoffe |
-
2003
- 2003-06-02 CN CNA038188511A patent/CN1675204A/zh active Pending
- 2003-06-02 CA CA2488761A patent/CA2488761C/en not_active Expired - Fee Related
- 2003-06-02 BR BR0312446-0A patent/BR0312446A/pt not_active Application Discontinuation
- 2003-06-02 DE DE50305587T patent/DE50305587D1/de not_active Expired - Lifetime
- 2003-06-02 JP JP2004511297A patent/JP4542891B2/ja not_active Expired - Fee Related
- 2003-06-02 AT AT03732517T patent/ATE344262T1/de not_active IP Right Cessation
- 2003-06-02 PL PL03374551A patent/PL374551A1/xx not_active Application Discontinuation
- 2003-06-02 MX MXPA04012439A patent/MXPA04012439A/es unknown
- 2003-06-02 US US10/516,777 patent/US7977485B2/en not_active Expired - Fee Related
- 2003-06-02 AU AU2003238450A patent/AU2003238450A1/en not_active Abandoned
- 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 EP EP03732517A patent/EP1515967B1/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 |
|---|---|
| CA2488761A1 (en) | 2003-12-18 |
| US20120258964A1 (en) | 2012-10-11 |
| CA2488761C (en) | 2011-05-31 |
| US9067931B2 (en) | 2015-06-30 |
| JP4542891B2 (ja) | 2010-09-15 |
| UY27841A1 (es) | 2003-12-31 |
| PL374551A1 (en) | 2005-10-31 |
| US7977485B2 (en) | 2011-07-12 |
| ATE344262T1 (de) | 2006-11-15 |
| DE50305587D1 (en) | 2006-12-14 |
| BR0312446A (pt) | 2005-04-19 |
| JP2005533052A (ja) | 2005-11-04 |
| EP1515967B1 (de) | 2006-11-02 |
| US20140350008A1 (en) | 2014-11-27 |
| US20060160877A1 (en) | 2006-07-20 |
| CN1675204A (zh) | 2005-09-28 |
| MXPA04012439A (es) | 2005-04-19 |
| US20110263591A1 (en) | 2011-10-27 |
| WO2003104227A1 (de) | 2003-12-18 |
| US20160122337A1 (en) | 2016-05-05 |
| IL165505A0 (en) | 2006-01-15 |
| NO20050063L (no) | 2005-01-06 |
| US10214524B2 (en) | 2019-02-26 |
| EP1515967A1 (de) | 2005-03-23 |
| ES2276072T3 (es) | 2007-06-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10214524B2 (en) | 2-heteroaryl carboxamides | |
| CA2471593C (en) | 2-heteroarylcarboxamides | |
| US6599916B2 (en) | Quinuclidine-substituted heteroaryl moieties for treatment of disease | |
| US6500840B2 (en) | Quinuclidine-substituted heteroaryl moieties for treatment of disease | |
| CA2479103C (en) | 1-azabicyclic n-biarylamides with affinity for the alpha7 nicotinic acetylcholine receptor | |
| US6492385B2 (en) | Quinuclidine-substituted heteroaryl moieties for treatment of disease | |
| US20070010556A1 (en) | Thiophene derivatives as chk 1 inhibitors | |
| JP4601424B2 (ja) | ベンゾチオフェン尿素、ベンゾフラン尿素およびインドール尿素、並びにアルファ７−ＡｃｈＲアゴニストとしてのそれらの使用 | |
| EP1311505A2 (en) | Quinuclidine-substituted heteroaryl moieties for treatment of disease ( nicotinic acetylcholine receptor ligands ) | |
| EP3380469A1 (en) | Bicyclic bet bromodomain inhibitors and uses thereof | |
| US20080051463A1 (en) | Anthracene compounds and their use for treating benign and malignant tumor disorders | |
| DE10305922A1 (de) | 2-Heteroarylcarbonsäureamide | |
| JP4813357B2 (ja) | Ｎ−ビアリールアミド化合物 | |
| HRP20050012A2 (hr) | 2-heteroarilni karboksamidi | |
| KR20050016531A (ko) | 2-헤테로아릴 카르복사미드 | |
| AU2012202307B2 (en) | Muscarinic acetylcholine receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |