PT2271650E - Compostos de quinuclidina como ligandos de recetor de acetilcolina alfa-7-nicotínica - Google Patents
Compostos de quinuclidina como ligandos de recetor de acetilcolina alfa-7-nicotínica Download PDFInfo
- Publication number
- PT2271650E PT2271650E PT97339493T PT09733949T PT2271650E PT 2271650 E PT2271650 E PT 2271650E PT 97339493 T PT97339493 T PT 97339493T PT 09733949 T PT09733949 T PT 09733949T PT 2271650 E PT2271650 E PT 2271650E
- Authority
- PT
- Portugal
- Prior art keywords
- mmol
- amine
- pyrimidinyl
- methyl
- octan
- Prior art date
Links
- 239000003446 ligand Substances 0.000 title description 5
- 102000047725 alpha7 Nicotinic Acetylcholine Receptor Human genes 0.000 title 1
- 108700006085 alpha7 Nicotinic Acetylcholine Receptor Proteins 0.000 title 1
- 150000008584 quinuclidines Chemical class 0.000 title 1
- -1 2-indolonyl Chemical group 0.000 claims description 684
- 229910052739 hydrogen Inorganic materials 0.000 claims description 173
- 150000001875 compounds Chemical class 0.000 claims description 83
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 21
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 14
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- HDCXQTPVTAIPNZ-UHFFFAOYSA-N n-({[4-(aminosulfonyl)phenyl]amino}carbonyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NC1=CC=C(S(N)(=O)=O)C=C1 HDCXQTPVTAIPNZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- 125000006396 chloropyrazinyl group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000006402 chloropyridazinyl group Chemical group 0.000 claims description 3
- 125000006390 chloropyrimidinyl group Chemical group 0.000 claims description 3
- 125000006399 methylpyrazinyl group Chemical group 0.000 claims description 3
- 125000006393 methylpyrimidinyl group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000006405 methylpyridazinyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 239000012964 benzotriazole Substances 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 150000003852 triazoles Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 466
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 391
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 303
- 239000000203 mixture Substances 0.000 description 244
- 238000006243 chemical reaction Methods 0.000 description 231
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 186
- 238000005481 NMR spectroscopy Methods 0.000 description 184
- 235000019439 ethyl acetate Nutrition 0.000 description 162
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 159
- 239000007787 solid Substances 0.000 description 149
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 148
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 123
- 239000000047 product Substances 0.000 description 121
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 118
- 239000000843 powder Substances 0.000 description 102
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
- 239000000243 solution Substances 0.000 description 87
- 238000000034 method Methods 0.000 description 68
- 239000011541 reaction mixture Substances 0.000 description 67
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 66
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 64
- 238000005160 1H NMR spectroscopy Methods 0.000 description 61
- 238000010898 silica gel chromatography Methods 0.000 description 61
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- 239000012043 crude product Substances 0.000 description 49
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 44
- 235000011114 ammonium hydroxide Nutrition 0.000 description 43
- 239000000908 ammonium hydroxide Substances 0.000 description 42
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 239000002244 precipitate Substances 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 35
- 239000000725 suspension Substances 0.000 description 35
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000003921 oil Substances 0.000 description 34
- 229910052938 sodium sulfate Inorganic materials 0.000 description 34
- 235000011152 sodium sulphate Nutrition 0.000 description 34
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 238000004587 chromatography analysis Methods 0.000 description 32
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- 238000004440 column chromatography Methods 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 28
- 239000010410 layer Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 238000003818 flash chromatography Methods 0.000 description 26
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 26
- KXMMNJQMGILZDB-UHFFFAOYSA-N 1-(2-oxopyridine-1-carbothioyl)pyridin-2-one Chemical compound O=C1C=CC=CN1C(=S)N1C(=O)C=CC=C1 KXMMNJQMGILZDB-UHFFFAOYSA-N 0.000 description 25
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 235000019341 magnesium sulphate Nutrition 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000013058 crude material Substances 0.000 description 24
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- OUKVGTYIZUXBIR-JZGIKJSDSA-N [(3s)-3-hydroxy-1-azoniabicyclo[2.2.2]octan-3-yl]methylazanium;dichloride Chemical compound Cl.Cl.C1CC2[C@@](CN)(O)CN1CC2 OUKVGTYIZUXBIR-JZGIKJSDSA-N 0.000 description 22
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- 229910000024 caesium carbonate Inorganic materials 0.000 description 21
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 21
- 238000004809 thin layer chromatography Methods 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 238000001914 filtration Methods 0.000 description 20
- 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 19
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 19
- 239000012071 phase Substances 0.000 description 19
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 18
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 235000011089 carbon dioxide Nutrition 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- 230000003287 optical effect Effects 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- DUKKRSPKJMHASP-UHFFFAOYSA-N 6-chloropyrimidin-4-amine Chemical compound NC1=CC(Cl)=NC=N1 DUKKRSPKJMHASP-UHFFFAOYSA-N 0.000 description 12
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- UONKGCZCROZZCD-QMMMGPOBSA-N (3s)-3-(aminomethyl)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@](CN)(O)CN1CC2 UONKGCZCROZZCD-QMMMGPOBSA-N 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 239000004202 carbamide Substances 0.000 description 10
- 238000012512 characterization method Methods 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 10
- 108091006146 Channels Proteins 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 9
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 208000015122 neurodegenerative disease Diseases 0.000 description 7
- 208000019022 Mood disease Diseases 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- ZGGNERQUFKZVBA-UHFFFAOYSA-N azanium;chloroform;hydroxide Chemical compound [NH4+].[OH-].ClC(Cl)Cl ZGGNERQUFKZVBA-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- YKOUABZEDZDJEY-UHFFFAOYSA-N methyl 2,2-diethoxyethanimidate Chemical compound CCOC(OCC)C(=N)OC YKOUABZEDZDJEY-UHFFFAOYSA-N 0.000 description 6
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 6
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- ADKICMRIVXDIOP-UHFFFAOYSA-N 4-isothiocyanato-6-methoxypyrimidine Chemical compound COC1=CC(N=C=S)=NC=N1 ADKICMRIVXDIOP-UHFFFAOYSA-N 0.000 description 5
- KRRTXVSBTPCDOS-UHFFFAOYSA-N 5-bromopyrazin-2-amine Chemical compound NC1=CN=C(Br)C=N1 KRRTXVSBTPCDOS-UHFFFAOYSA-N 0.000 description 5
- VPRKGLYZWQCCHU-UHFFFAOYSA-N 6-pyridin-3-ylpyrimidin-4-amine Chemical compound C1=NC(N)=CC(C=2C=NC=CC=2)=N1 VPRKGLYZWQCCHU-UHFFFAOYSA-N 0.000 description 5
- 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 5
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 5
- 229960004373 acetylcholine Drugs 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 229940045348 brown mixture Drugs 0.000 description 5
- FKGQRXQOODICAT-UHFFFAOYSA-N di(imidazol-1-yl)methanimine Chemical compound C1=CN=CN1C(=N)N1C=CN=C1 FKGQRXQOODICAT-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 4
- PXWGDZJDUOPMGQ-IBGZPJMESA-N (3r)-n-(6-phenylpyridazin-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(N=N1)=CC=C1C1=CC=CC=C1 PXWGDZJDUOPMGQ-IBGZPJMESA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- LLPVJZMTIYQTGU-UHFFFAOYSA-N 5-methoxy-[1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound COC1=CC=C2N=C(N)SC2=N1 LLPVJZMTIYQTGU-UHFFFAOYSA-N 0.000 description 4
- BLGYAIWJMVWVDS-UHFFFAOYSA-N 6-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-amine Chemical compound C1=C(OC)C=CC2=NC(N)=NN21 BLGYAIWJMVWVDS-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 102000004310 Ion Channels Human genes 0.000 description 4
- 108090000862 Ion Channels Proteins 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- MCLJDHWIDXKUBS-UHFFFAOYSA-N bicyclo[2.2.2]octan-3-amine Chemical compound C1CC2C(N)CC1CC2 MCLJDHWIDXKUBS-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 150000002540 isothiocyanates Chemical class 0.000 description 4
- PSQGPXUZFGQICZ-UHFFFAOYSA-N n'-[(2,4-dichlorophenyl)methyl]-2,2-diethoxyethanimidamide Chemical compound CCOC(OCC)C(=N)NCC1=CC=C(Cl)C=C1Cl PSQGPXUZFGQICZ-UHFFFAOYSA-N 0.000 description 4
- 229960002715 nicotine Drugs 0.000 description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
- HBXNJMZWGSCKPW-UHFFFAOYSA-N octan-2-amine Chemical compound CCCCCCC(C)N HBXNJMZWGSCKPW-UHFFFAOYSA-N 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229940116357 potassium thiocyanate Drugs 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- LENPKGRPSYLBFA-ZDUSSCGKSA-N (3r)-n-(6-chloropyridazin-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound N1=NC(Cl)=CC=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 LENPKGRPSYLBFA-ZDUSSCGKSA-N 0.000 description 3
- OHUNPVCHRGBDHH-AWEZNQCLSA-N (3r)-n-(6-methoxypyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=NC(OC)=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=N1 OHUNPVCHRGBDHH-AWEZNQCLSA-N 0.000 description 3
- NHLSXQSQHXPPDQ-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-n-(5-phenylmethoxy-[1,3]thiazolo[5,4-b]pyridin-2-yl)methanimine Chemical compound N1=C2SC(N=C(SC)SC)=NC2=CC=C1OCC1=CC=CC=C1 NHLSXQSQHXPPDQ-UHFFFAOYSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- JPBLHOJFMBOCAF-UHFFFAOYSA-N 1,3-benzoxazol-2-amine Chemical compound C1=CC=C2OC(N)=NC2=C1 JPBLHOJFMBOCAF-UHFFFAOYSA-N 0.000 description 3
- FIBFRSFPAIRFOR-UHFFFAOYSA-N 1-(5-aminopyrazin-2-yl)pyrrolidin-2-one Chemical compound C1=NC(N)=CN=C1N1C(=O)CCC1 FIBFRSFPAIRFOR-UHFFFAOYSA-N 0.000 description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- WLHADOSXRICWAB-UHFFFAOYSA-N 2-(difluoromethoxy)-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(OC(F)F)N=C1 WLHADOSXRICWAB-UHFFFAOYSA-N 0.000 description 3
- VSOBZMWGTWAHSR-UHFFFAOYSA-N 2-bromo-6-isothiocyanatopyridine Chemical compound BrC1=CC=CC(N=C=S)=N1 VSOBZMWGTWAHSR-UHFFFAOYSA-N 0.000 description 3
- WTSWSBPEZJCSMC-UHFFFAOYSA-N 2-chloro-5-(difluoromethoxy)pyrimidine Chemical compound FC(F)OC1=CN=C(Cl)N=C1 WTSWSBPEZJCSMC-UHFFFAOYSA-N 0.000 description 3
- MANHSBQXHPLZSR-UHFFFAOYSA-N 2-chloro-5-cyclopentyloxypyrimidine Chemical compound C1=NC(Cl)=NC=C1OC1CCCC1 MANHSBQXHPLZSR-UHFFFAOYSA-N 0.000 description 3
- SXUWYCHACCYVMS-UHFFFAOYSA-N 2-chloro-6-methoxyquinoxaline Chemical compound N1=C(Cl)C=NC2=CC(OC)=CC=C21 SXUWYCHACCYVMS-UHFFFAOYSA-N 0.000 description 3
- DKHLVVSSFRDDKS-UHFFFAOYSA-N 3,5-dichloro-2-isothiocyanatopyridine Chemical compound ClC1=CN=C(N=C=S)C(Cl)=C1 DKHLVVSSFRDDKS-UHFFFAOYSA-N 0.000 description 3
- WSGPQEKGIAKLME-UHFFFAOYSA-N 3-isothiocyanato-6,8-dimethylisoquinoline Chemical compound C1=NC(N=C=S)=CC2=CC(C)=CC(C)=C21 WSGPQEKGIAKLME-UHFFFAOYSA-N 0.000 description 3
- HPDLWLVRGCHZGT-UHFFFAOYSA-N 3-isothiocyanato-6-methylisoquinoline Chemical compound C1=NC(N=C=S)=CC2=CC(C)=CC=C21 HPDLWLVRGCHZGT-UHFFFAOYSA-N 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- PFCDPPOYVKKKCP-UHFFFAOYSA-N 4,5-dichloro-2-isothiocyanatopyridine Chemical compound ClC1=CN=C(N=C=S)C=C1Cl PFCDPPOYVKKKCP-UHFFFAOYSA-N 0.000 description 3
- IELZPOFKHRZRGS-UHFFFAOYSA-N 4,5-dimethylpyrimidin-2-amine Chemical compound CC1=CN=C(N)N=C1C IELZPOFKHRZRGS-UHFFFAOYSA-N 0.000 description 3
- IUNZNINLPZAQDM-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-isothiocyanatopyrimidine Chemical compound ClC1=CC=CC(C=2N=CN=C(N=C=S)C=2)=C1 IUNZNINLPZAQDM-UHFFFAOYSA-N 0.000 description 3
- CJTDPEZNGURNJL-UHFFFAOYSA-N 4-chloro-6-(2,2,2-trifluoroethoxy)pyrimidine Chemical compound FC(F)(F)COC1=CC(Cl)=NC=N1 CJTDPEZNGURNJL-UHFFFAOYSA-N 0.000 description 3
- QOOQUMTZWQEHTR-UHFFFAOYSA-N 4-chloro-6-(methoxymethyl)pyrimidine Chemical compound COCC1=CC(Cl)=NC=N1 QOOQUMTZWQEHTR-UHFFFAOYSA-N 0.000 description 3
- DQHCEDCSEAGFRM-UHFFFAOYSA-N 4-chloro-6-cyclopentyloxypyrimidine Chemical compound C1=NC(Cl)=CC(OC2CCCC2)=N1 DQHCEDCSEAGFRM-UHFFFAOYSA-N 0.000 description 3
- YYHYJXGSBDBGSF-UHFFFAOYSA-N 4-isothiocyanato-6-(3-methoxyphenyl)pyrimidine Chemical compound COC1=CC=CC(C=2N=CN=C(N=C=S)C=2)=C1 YYHYJXGSBDBGSF-UHFFFAOYSA-N 0.000 description 3
- ABIDGJQJJGUVID-UHFFFAOYSA-N 4-isothiocyanato-6-phenoxypyrimidine Chemical compound C1=NC(N=C=S)=CC(OC=2C=CC=CC=2)=N1 ABIDGJQJJGUVID-UHFFFAOYSA-N 0.000 description 3
- CIIVQXITBPFBAK-UHFFFAOYSA-N 4-isothiocyanato-6-pyridin-4-ylpyrimidine Chemical compound C1=NC(N=C=S)=CC(C=2C=CN=CC=2)=N1 CIIVQXITBPFBAK-UHFFFAOYSA-N 0.000 description 3
- AVRNZAITOUMSPB-UHFFFAOYSA-N 4-propan-2-ylpyrimidin-2-amine Chemical compound CC(C)C1=CC=NC(N)=N1 AVRNZAITOUMSPB-UHFFFAOYSA-N 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 3
- IKECPQGVQXXBSD-UHFFFAOYSA-N 5,6-dichloro-3-isothiocyanatoisoquinoline Chemical compound C1=NC(N=C=S)=CC2=C(Cl)C(Cl)=CC=C21 IKECPQGVQXXBSD-UHFFFAOYSA-N 0.000 description 3
- YTDSLQOPAQVPKD-UHFFFAOYSA-N 5,6-dichloroisoquinolin-3-amine Chemical compound ClC1=CC=C2C=NC(N)=CC2=C1Cl YTDSLQOPAQVPKD-UHFFFAOYSA-N 0.000 description 3
- LULBBYYBHKFKBH-UHFFFAOYSA-N 5,6-dichloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C(Cl)=N1 LULBBYYBHKFKBH-UHFFFAOYSA-N 0.000 description 3
- LWYPLPIJTCQWCF-UHFFFAOYSA-N 5-(difluoromethoxy)-[1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound C1=C(OC(F)F)N=C2SC(N)=NC2=C1 LWYPLPIJTCQWCF-UHFFFAOYSA-N 0.000 description 3
- ILDRNIDSVAZBMZ-UHFFFAOYSA-N 5-(trifluoromethyl)pyrazin-2-amine Chemical compound NC1=CN=C(C(F)(F)F)C=N1 ILDRNIDSVAZBMZ-UHFFFAOYSA-N 0.000 description 3
- UNAQXMQWXKKBEK-UHFFFAOYSA-N 5-chloro-2-isothiocyanato-4-methylpyridine Chemical compound CC1=CC(N=C=S)=NC=C1Cl UNAQXMQWXKKBEK-UHFFFAOYSA-N 0.000 description 3
- KFKXUFHFJAKEKI-UHFFFAOYSA-N 5-methoxy-[1,3]thiazolo[5,4-d]pyrimidin-2-amine Chemical compound COC1=NC=C2N=C(N)SC2=N1 KFKXUFHFJAKEKI-UHFFFAOYSA-N 0.000 description 3
- BAXUDPKGRMMFBV-UHFFFAOYSA-N 5-phenylpyridin-3-amine Chemical compound NC1=CN=CC(C=2C=CC=CC=2)=C1 BAXUDPKGRMMFBV-UHFFFAOYSA-N 0.000 description 3
- XSYBQTMVQZSLGQ-UHFFFAOYSA-N 5-pyrrolidin-1-ylpyrazin-2-amine Chemical compound C1=NC(N)=CN=C1N1CCCC1 XSYBQTMVQZSLGQ-UHFFFAOYSA-N 0.000 description 3
- UAKAFAPSKXVOLF-UHFFFAOYSA-N 6,7-dichloro-3-isothiocyanatoisoquinoline Chemical compound N1=C(N=C=S)C=C2C=C(Cl)C(Cl)=CC2=C1 UAKAFAPSKXVOLF-UHFFFAOYSA-N 0.000 description 3
- QQKNHPWFFIATKE-UHFFFAOYSA-N 6,8-dimethylisoquinolin-3-amine Chemical compound C1=NC(N)=CC2=CC(C)=CC(C)=C21 QQKNHPWFFIATKE-UHFFFAOYSA-N 0.000 description 3
- TUABPDBZFQJDHM-UHFFFAOYSA-N 6-(3-methoxyphenyl)pyrimidin-4-amine Chemical compound COC1=CC=CC(C=2N=CN=C(N)C=2)=C1 TUABPDBZFQJDHM-UHFFFAOYSA-N 0.000 description 3
- PUXOOQNLQPZQFB-UHFFFAOYSA-N 6-(difluoromethoxy)-1,3-benzothiazol-2-amine Chemical compound C1=C(OC(F)F)C=C2SC(N)=NC2=C1 PUXOOQNLQPZQFB-UHFFFAOYSA-N 0.000 description 3
- LHRMIXPETPBOOD-UHFFFAOYSA-N 6-(difluoromethoxy)-1-methylindazol-3-amine Chemical compound C1=C(OC(F)F)C=C2N(C)N=C(N)C2=C1 LHRMIXPETPBOOD-UHFFFAOYSA-N 0.000 description 3
- LZPYGFBASUNYEY-UHFFFAOYSA-N 6-(difluoromethoxy)pyridin-3-amine Chemical compound NC1=CC=C(OC(F)F)N=C1 LZPYGFBASUNYEY-UHFFFAOYSA-N 0.000 description 3
- TUWLYFAEAPMOJS-UHFFFAOYSA-N 6-(methoxymethyl)-1h-pyrimidin-4-one Chemical compound COCC1=CC(O)=NC=N1 TUWLYFAEAPMOJS-UHFFFAOYSA-N 0.000 description 3
- BKLJUYPLUWUEOQ-UHFFFAOYSA-N 6-bromopyridin-2-amine Chemical compound NC1=CC=CC(Br)=N1 BKLJUYPLUWUEOQ-UHFFFAOYSA-N 0.000 description 3
- JKOGFRGFWFEFNT-UHFFFAOYSA-N 6-fluoro-1h-indazol-3-amine Chemical compound FC1=CC=C2C(N)=NNC2=C1 JKOGFRGFWFEFNT-UHFFFAOYSA-N 0.000 description 3
- QZPQDBMKUYEGQK-UHFFFAOYSA-N 6-fluoro-3-isothiocyanato-1h-indazole Chemical compound FC1=CC=C2C(N=C=S)=NNC2=C1 QZPQDBMKUYEGQK-UHFFFAOYSA-N 0.000 description 3
- YZSMZWMPCQWUOQ-UHFFFAOYSA-N 6-isothiocyanato-2,4-dimethylpyridine-3-carbonitrile Chemical compound CC1=CC(N=C=S)=NC(C)=C1C#N YZSMZWMPCQWUOQ-UHFFFAOYSA-N 0.000 description 3
- WTTQQWHDRLGJSP-UHFFFAOYSA-N 6-isothiocyanato-2-methylpyridine-3-carbonitrile Chemical compound CC1=NC(N=C=S)=CC=C1C#N WTTQQWHDRLGJSP-UHFFFAOYSA-N 0.000 description 3
- SYEUUDPGKMMKRU-UHFFFAOYSA-N 6-methoxy-1h-quinoxalin-2-one Chemical compound N1C(=O)C=NC2=CC(OC)=CC=C21 SYEUUDPGKMMKRU-UHFFFAOYSA-N 0.000 description 3
- DBOBOPSSKJMSSY-UHFFFAOYSA-N 6-methylisoquinolin-3-amine Chemical compound C1=NC(N)=CC2=CC(C)=CC=C21 DBOBOPSSKJMSSY-UHFFFAOYSA-N 0.000 description 3
- QOBXQIQOGCQMTH-UHFFFAOYSA-N 6-methylquinoxalin-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=C(N)C=NC2=CC(C)=CC=C21 QOBXQIQOGCQMTH-UHFFFAOYSA-N 0.000 description 3
- VZXLYMCMLMJTEI-UHFFFAOYSA-N 6-phenoxypyrimidin-4-amine Chemical compound C1=NC(N)=CC(OC=2C=CC=CC=2)=N1 VZXLYMCMLMJTEI-UHFFFAOYSA-N 0.000 description 3
- NYXYYBHDSNBGOS-UHFFFAOYSA-N 6-phenylpyrimidin-4-amine Chemical compound C1=NC(N)=CC(C=2C=CC=CC=2)=N1 NYXYYBHDSNBGOS-UHFFFAOYSA-N 0.000 description 3
- GVERQUMLAYWTMA-UHFFFAOYSA-N 7-methoxy-1h-quinoxalin-2-one Chemical compound N1=CC(O)=NC2=CC(OC)=CC=C21 GVERQUMLAYWTMA-UHFFFAOYSA-N 0.000 description 3
- CUOUUOGXWPOSHD-UHFFFAOYSA-N 7-methoxy-5-methyl-[1,3]thiazolo[5,4-d]pyrimidin-2-amine Chemical compound COC1=NC(C)=NC2=C1N=C(N)S2 CUOUUOGXWPOSHD-UHFFFAOYSA-N 0.000 description 3
- DKJWBGHKXDXECN-UHFFFAOYSA-N 7-methoxyquinoxalin-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC(N)=NC2=CC(OC)=CC=C21 DKJWBGHKXDXECN-UHFFFAOYSA-N 0.000 description 3
- ODGPJSALOCAXRG-UHFFFAOYSA-N 7-methylquinoxalin-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC(N)=NC2=CC(C)=CC=C21 ODGPJSALOCAXRG-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 102000009660 Cholinergic Receptors Human genes 0.000 description 3
- 108010009685 Cholinergic Receptors Proteins 0.000 description 3
- 241001136616 Methone Species 0.000 description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 235000011148 calcium chloride Nutrition 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000003920 cognitive function Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- VVFKWBPGTKRJDO-UHFFFAOYSA-N ethyl n-(7-chloro-5-methyl-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)carbamate Chemical compound N1=C(C)N=C2SC(NC(=O)OCC)=NC2=C1Cl VVFKWBPGTKRJDO-UHFFFAOYSA-N 0.000 description 3
- BDTDECDAHYOJRO-UHFFFAOYSA-N ethyl n-(sulfanylidenemethylidene)carbamate Chemical compound CCOC(=O)N=C=S BDTDECDAHYOJRO-UHFFFAOYSA-N 0.000 description 3
- FKZUMAMNRPWLKP-UHFFFAOYSA-N ethyl n-[5-(dimethylamino)-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]carbamate Chemical compound N1=C(N(C)C)N=C2SC(NC(=O)OCC)=NC2=C1 FKZUMAMNRPWLKP-UHFFFAOYSA-N 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000015654 memory Effects 0.000 description 3
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 3
- 239000007758 minimum essential medium Substances 0.000 description 3
- MWGISGHYSNLOIO-UHFFFAOYSA-N n'-[(3,4-dichlorophenyl)methyl]-2,2-diethoxyethanimidamide Chemical compound CCOC(OCC)C(=N)NCC1=CC=C(Cl)C(Cl)=C1 MWGISGHYSNLOIO-UHFFFAOYSA-N 0.000 description 3
- RPGSTSWVRNPAKP-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound N=1C2=CC=CC=C2SC=1NC(=S)N1C=CN=C1 RPGSTSWVRNPAKP-UHFFFAOYSA-N 0.000 description 3
- NYKOHJDWRQIEQZ-UHFFFAOYSA-N n-(3-methyl-1,2,4-oxadiazol-5-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound CSC(SC)=NC1=NC(C)=NO1 NYKOHJDWRQIEQZ-UHFFFAOYSA-N 0.000 description 3
- KYEKKLZQGRIPLQ-UHFFFAOYSA-N n-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound N=1C=2CCCCC=2SC=1NC(=S)N1C=CN=C1 KYEKKLZQGRIPLQ-UHFFFAOYSA-N 0.000 description 3
- YPYBXVUXWWJIND-UHFFFAOYSA-N n-(4-chloro-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound N=1C=2C(Cl)=CC=CC=2SC=1NC(=S)N1C=CN=C1 YPYBXVUXWWJIND-UHFFFAOYSA-N 0.000 description 3
- MTIALXJECNTTKZ-UHFFFAOYSA-N n-(5,6-dichloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=C(Cl)C(Cl)=N1 MTIALXJECNTTKZ-UHFFFAOYSA-N 0.000 description 3
- CKYGNDBIVBKWDQ-UHFFFAOYSA-N n-(5-chloro-1,3-benzoxazol-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound ClC1=CC=C2OC(N=C(SC)SC)=NC2=C1 CKYGNDBIVBKWDQ-UHFFFAOYSA-N 0.000 description 3
- BIRKZPAWNVZXGA-UHFFFAOYSA-N n-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound C1=C(Cl)N=C2SC(N=C(SC)SC)=NC2=C1 BIRKZPAWNVZXGA-UHFFFAOYSA-N 0.000 description 3
- RSAYOWHRLDBGBO-UHFFFAOYSA-N n-(5-ethyl-1,3,4-oxadiazol-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound CCC1=NN=C(N=C(SC)SC)O1 RSAYOWHRLDBGBO-UHFFFAOYSA-N 0.000 description 3
- CXQLQGQCIQXZMI-UHFFFAOYSA-N n-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound CSC(SC)=NC1=NN=C(C)O1 CXQLQGQCIQXZMI-UHFFFAOYSA-N 0.000 description 3
- URWMDWYEUVQFRS-UHFFFAOYSA-N n-(6-bromo-[1,3]thiazolo[4,5-b]pyrazin-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound C1=C(Br)N=C2SC(N=C(SC)SC)=NC2=N1 URWMDWYEUVQFRS-UHFFFAOYSA-N 0.000 description 3
- VWTRVYZJIAPBHR-UHFFFAOYSA-N n-(6-chloro-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound S1C2=CC(Cl)=CC=C2N=C1NC(=S)N1C=CN=C1 VWTRVYZJIAPBHR-UHFFFAOYSA-N 0.000 description 3
- NTKLQWVHHBNEPH-UHFFFAOYSA-N n-[(2,4-dimethoxyphenyl)methyl]-7-methoxyquinoxalin-2-amine Chemical compound COC1=CC(OC)=CC=C1CNC1=CN=C(C=CC(OC)=C2)C2=N1 NTKLQWVHHBNEPH-UHFFFAOYSA-N 0.000 description 3
- PMMRCUFGSCVKGZ-UHFFFAOYSA-N n-[(2,4-dimethoxyphenyl)methyl]-7-methylquinoxalin-2-amine Chemical compound COC1=CC(OC)=CC=C1CNC1=CN=C(C=CC(C)=C2)C2=N1 PMMRCUFGSCVKGZ-UHFFFAOYSA-N 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- YBNVZMAWKRAQOR-UHFFFAOYSA-N pyrazin-2-yl carbamodithioate Chemical compound C(N)(SC1=NC=CN=C1)=S YBNVZMAWKRAQOR-UHFFFAOYSA-N 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 230000000698 schizophrenic effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 2
- VPUPAKNLGRLWBT-QRPNPIFTSA-N (3S)-3-(aminomethyl)-1-azabicyclo[2.2.2]octan-3-ol hydrochloride Chemical compound Cl.C1CC2[C@@](CN)(O)CN1CC2 VPUPAKNLGRLWBT-QRPNPIFTSA-N 0.000 description 2
- XUVWKYXUAQLACT-AWEZNQCLSA-N (3r)-n-(3,4-dichloropyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound ClC1=CC=NC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=C1Cl XUVWKYXUAQLACT-AWEZNQCLSA-N 0.000 description 2
- FTKSVULOEFWVKD-AWEZNQCLSA-N (3r)-n-(3-chloropyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound ClC1=CC=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 FTKSVULOEFWVKD-AWEZNQCLSA-N 0.000 description 2
- RJXPRKOQFMLVFU-AWEZNQCLSA-N (3r)-n-(4,6-dichloropyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound ClC1=CC(Cl)=NC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=C1 RJXPRKOQFMLVFU-AWEZNQCLSA-N 0.000 description 2
- HWESYGNLBMIHIM-AWEZNQCLSA-N (3r)-n-(5-methylsulfanylpyrazin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=NC(SC)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 HWESYGNLBMIHIM-AWEZNQCLSA-N 0.000 description 2
- AMXYESZREAWKMZ-AWEZNQCLSA-N (3r)-n-(6-methylsulfanylpyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=NC(SC)=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=N1 AMXYESZREAWKMZ-AWEZNQCLSA-N 0.000 description 2
- WLYKLHKTDTYDLH-INIZCTEOSA-N (3r)-n-(6-propan-2-yloxypyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=NC(OC(C)C)=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=N1 WLYKLHKTDTYDLH-INIZCTEOSA-N 0.000 description 2
- ZIXIFHSPOBDBRO-ZDUSSCGKSA-N (3r)-n-[5-(trifluoromethyl)pyrazin-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=NC(C(F)(F)F)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 ZIXIFHSPOBDBRO-ZDUSSCGKSA-N 0.000 description 2
- VEGLDOGYVHCXAC-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-n-(3-methyl-1,2,4-thiadiazol-5-yl)methanimine Chemical compound CSC(SC)=NC1=NC(C)=NS1 VEGLDOGYVHCXAC-UHFFFAOYSA-N 0.000 description 2
- OBSLLHNATPQFMJ-UHFFFAOYSA-N 2,4-Dimethylthiazole Chemical compound CC1=CSC(C)=N1 OBSLLHNATPQFMJ-UHFFFAOYSA-N 0.000 description 2
- KTTRCCNEXRHBNT-ZDUSSCGKSA-N 2-[[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-yl]amino]-1,3-thiazole-5-carbonitrile Chemical compound S1C(C#N)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 KTTRCCNEXRHBNT-ZDUSSCGKSA-N 0.000 description 2
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
- FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 2
- BOGPIHXNWPTGNH-UHFFFAOYSA-N 2-chloropyrimidin-5-ol Chemical compound OC1=CN=C(Cl)N=C1 BOGPIHXNWPTGNH-UHFFFAOYSA-N 0.000 description 2
- UCMJVPUVABQMFV-UHFFFAOYSA-N 2-isothiocyanato-4-(2-methoxypyridin-3-yl)pyridine Chemical compound COC1=NC=CC=C1C1=CC=NC(N=C=S)=C1 UCMJVPUVABQMFV-UHFFFAOYSA-N 0.000 description 2
- WUACEPTXSRKMEX-UHFFFAOYSA-N 2-isothiocyanato-5-methylsulfanylpyrazine Chemical compound CSC1=CN=C(N=C=S)C=N1 WUACEPTXSRKMEX-UHFFFAOYSA-N 0.000 description 2
- ZZQSEVQIMITDMU-UHFFFAOYSA-N 2-isothiocyanato-6-methylquinoxaline Chemical compound N1=C(N=C=S)C=NC2=CC(C)=CC=C21 ZZQSEVQIMITDMU-UHFFFAOYSA-N 0.000 description 2
- KBFBGQUDRKPWIP-UHFFFAOYSA-N 2-isothiocyanato-7-methoxyquinoxaline Chemical compound N1=CC(N=C=S)=NC2=CC(OC)=CC=C21 KBFBGQUDRKPWIP-UHFFFAOYSA-N 0.000 description 2
- UONKGCZCROZZCD-UHFFFAOYSA-N 3-(aminomethyl)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2C(CN)(O)CN1CC2 UONKGCZCROZZCD-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- MQTXWBGYHOTVHZ-UHFFFAOYSA-N 3-bromo-6-isothiocyanatopyridazine Chemical compound BrC1=CC=C(N=C=S)N=N1 MQTXWBGYHOTVHZ-UHFFFAOYSA-N 0.000 description 2
- OHOUDXWKMDOAPQ-UHFFFAOYSA-N 3-chloro-6-isothiocyanatopyridazine Chemical compound ClC1=CC=C(N=C=S)N=N1 OHOUDXWKMDOAPQ-UHFFFAOYSA-N 0.000 description 2
- YQCXTUQBIQFUPE-UHFFFAOYSA-N 3-isothiocyanato-6-phenylpyridazine Chemical compound N1=NC(N=C=S)=CC=C1C1=CC=CC=C1 YQCXTUQBIQFUPE-UHFFFAOYSA-N 0.000 description 2
- UGMQFWDSELPKKP-UHFFFAOYSA-N 3-isothiocyanatoisoquinoline Chemical compound C1=CC=C2C=NC(N=C=S)=CC2=C1 UGMQFWDSELPKKP-UHFFFAOYSA-N 0.000 description 2
- DXZLXKWCQCYQBC-UHFFFAOYSA-N 4-(2-methoxypyridin-3-yl)pyridin-2-amine Chemical compound COC1=NC=CC=C1C1=CC=NC(N)=C1 DXZLXKWCQCYQBC-UHFFFAOYSA-N 0.000 description 2
- YKDAOJYJASPGDM-UHFFFAOYSA-N 4-(4-chlorophenyl)-6-isothiocyanatopyrimidine Chemical compound C1=CC(Cl)=CC=C1C1=CC(N=C=S)=NC=N1 YKDAOJYJASPGDM-UHFFFAOYSA-N 0.000 description 2
- OGBVYBGVSBZBLT-UHFFFAOYSA-N 4-isothiocyanato-6-pyridin-3-ylpyrimidine Chemical compound C1=NC(N=C=S)=CC(C=2C=NC=CC=2)=N1 OGBVYBGVSBZBLT-UHFFFAOYSA-N 0.000 description 2
- GSCRYWWEBZTTBF-UHFFFAOYSA-N 5-bromo-4-propan-2-ylpyrimidin-2-amine Chemical compound CC(C)C1=NC(N)=NC=C1Br GSCRYWWEBZTTBF-UHFFFAOYSA-N 0.000 description 2
- XGAKNUPZXKPFOS-UHFFFAOYSA-N 5-cyclopentyloxypyrimidin-2-amine Chemical compound C1=NC(N)=NC=C1OC1CCCC1 XGAKNUPZXKPFOS-UHFFFAOYSA-N 0.000 description 2
- XJKJHILCYUUVSJ-UHFFFAOYSA-N 5-methoxypyridin-2-amine Chemical compound COC1=CC=C(N)N=C1 XJKJHILCYUUVSJ-UHFFFAOYSA-N 0.000 description 2
- IPBKLPYWVRTALX-UHFFFAOYSA-N 5-methylsulfanylpyrazin-2-amine Chemical compound CSC1=CN=C(N)C=N1 IPBKLPYWVRTALX-UHFFFAOYSA-N 0.000 description 2
- VZKIMVYWEBBKGS-UHFFFAOYSA-N 5-phenylmethoxy-[1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound N1=C2SC(N)=NC2=CC=C1OCC1=CC=CC=C1 VZKIMVYWEBBKGS-UHFFFAOYSA-N 0.000 description 2
- SJGNIZFAJDLNQE-UHFFFAOYSA-N 5-pyridin-3-ylpyrazin-2-amine Chemical compound C1=NC(N)=CN=C1C1=CC=CN=C1 SJGNIZFAJDLNQE-UHFFFAOYSA-N 0.000 description 2
- SVFTZRIJBQMZKB-UHFFFAOYSA-N 6,7-dichloroisoquinolin-3-amine Chemical compound ClC1=C(Cl)C=C2C=NC(N)=CC2=C1 SVFTZRIJBQMZKB-UHFFFAOYSA-N 0.000 description 2
- DZTSGWULIRGYOJ-UHFFFAOYSA-N 6,8-dichloro-3-isothiocyanatoisoquinoline Chemical compound C1=NC(N=C=S)=CC2=CC(Cl)=CC(Cl)=C21 DZTSGWULIRGYOJ-UHFFFAOYSA-N 0.000 description 2
- JMRHKUHTNHRFON-UHFFFAOYSA-N 6,8-dichloroisoquinolin-3-amine Chemical compound ClC1=CC(Cl)=C2C=NC(N)=CC2=C1 JMRHKUHTNHRFON-UHFFFAOYSA-N 0.000 description 2
- KQJHSCZATVSGTO-UHFFFAOYSA-N 6-(2,2,2-trifluoroethoxy)pyrimidin-4-amine Chemical compound NC1=CC(OCC(F)(F)F)=NC=N1 KQJHSCZATVSGTO-UHFFFAOYSA-N 0.000 description 2
- ZYQBVXRVGUVSCW-UHFFFAOYSA-N 6-(3-chlorophenyl)pyrimidin-4-amine Chemical compound C1=NC(N)=CC(C=2C=C(Cl)C=CC=2)=N1 ZYQBVXRVGUVSCW-UHFFFAOYSA-N 0.000 description 2
- ZEEJRACEEDQANN-UHFFFAOYSA-N 6-(methoxymethyl)pyrimidin-4-amine Chemical compound COCC1=CC(N)=NC=N1 ZEEJRACEEDQANN-UHFFFAOYSA-N 0.000 description 2
- IKJPWKKDLNSXGW-UHFFFAOYSA-N 6-bromo-3-isothiocyanatoisoquinoline Chemical compound C1=NC(N=C=S)=CC2=CC(Br)=CC=C21 IKJPWKKDLNSXGW-UHFFFAOYSA-N 0.000 description 2
- PQKLBIXLXFRNKT-UHFFFAOYSA-N 6-bromoisoquinolin-3-amine Chemical compound BrC1=CC=C2C=NC(N)=CC2=C1 PQKLBIXLXFRNKT-UHFFFAOYSA-N 0.000 description 2
- IVIXRMWFVKQEBE-UHFFFAOYSA-N 6-cyclopentyloxypyrimidin-4-amine Chemical compound C1=NC(N)=CC(OC2CCCC2)=N1 IVIXRMWFVKQEBE-UHFFFAOYSA-N 0.000 description 2
- PPEJLOXOMBAXES-UHFFFAOYSA-N 6-methylisoquinoline Chemical compound C1=NC=CC2=CC(C)=CC=C21 PPEJLOXOMBAXES-UHFFFAOYSA-N 0.000 description 2
- LEGHXWSIXMQCGW-UHFFFAOYSA-N 6-pyridin-4-ylpyrimidin-4-amine Chemical compound C1=NC(N)=CC(C=2C=CN=CC=2)=N1 LEGHXWSIXMQCGW-UHFFFAOYSA-N 0.000 description 2
- ZZYGROXOXBQBHP-UHFFFAOYSA-N 7-bromo-3-isothiocyanatoisoquinoline Chemical compound C1=C(N=C=S)N=CC2=CC(Br)=CC=C21 ZZYGROXOXBQBHP-UHFFFAOYSA-N 0.000 description 2
- FBTKUAFGTDENLW-UHFFFAOYSA-N 7-bromoisoquinolin-3-amine Chemical compound C1=C(Br)C=C2C=NC(N)=CC2=C1 FBTKUAFGTDENLW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 101710178035 Chorismate synthase 2 Proteins 0.000 description 2
- 101710152694 Cysteine synthase 2 Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 2
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- UUYSQAYUTMLLBO-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrazin-2-amine Chemical compound C1=NC=CN2N=C(N)N=C21 UUYSQAYUTMLLBO-UHFFFAOYSA-N 0.000 description 2
- NCZQAIFOXJOCFI-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyridin-3-amine Chemical compound C1=CC=CN2C(N)=NN=C21 NCZQAIFOXJOCFI-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- CAACGBPGDBJKFK-UHFFFAOYSA-N azanium;ethyl acetate;hydroxide Chemical compound [NH4+].[OH-].CCOC(C)=O CAACGBPGDBJKFK-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical group [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- MXDFPKDNQYNZPK-UHFFFAOYSA-N ethyl n-(5-chloro-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)carbamate Chemical compound N1=C(Cl)N=C2SC(NC(=O)OCC)=NC2=C1 MXDFPKDNQYNZPK-UHFFFAOYSA-N 0.000 description 2
- XFSYPTPQPTXLEF-UHFFFAOYSA-N ethyl n-carbamothioylcarbamate;5-methoxypyridin-2-amine Chemical compound CCOC(=O)NC(N)=S.COC1=CC=C(N)N=C1 XFSYPTPQPTXLEF-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- IWMQAUYDCYPLFK-UHFFFAOYSA-N furo[3,2-c]pyridin-4-amine Chemical compound NC1=NC=CC2=C1C=CO2 IWMQAUYDCYPLFK-UHFFFAOYSA-N 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 125000005241 heteroarylamino group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- SHTZWMUGTLYWKT-UHFFFAOYSA-N n'-[(3-bromophenyl)methyl]-2,2-diethoxyethanimidamide Chemical compound CCOC(OCC)C(=N)NCC1=CC=CC(Br)=C1 SHTZWMUGTLYWKT-UHFFFAOYSA-N 0.000 description 2
- XMJSRIGSOQCHNI-UHFFFAOYSA-N n-(1,3-thiazol-2-yl)imidazole-1-carbothioamide Chemical compound C1=CN=CN1C(=S)NC1=NC=CS1 XMJSRIGSOQCHNI-UHFFFAOYSA-N 0.000 description 2
- CWFZHFCDHUUVQO-UHFFFAOYSA-N n-(1h-benzimidazol-2-yl)imidazole-1-carbothioamide Chemical compound N=1C2=CC=CC=C2NC=1NC(=S)N1C=CN=C1 CWFZHFCDHUUVQO-UHFFFAOYSA-N 0.000 description 2
- NOALOJGCCOIRFR-UHFFFAOYSA-N n-(4-methyl-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound N=1C=2C(C)=CC=CC=2SC=1NC(=S)N1C=CN=C1 NOALOJGCCOIRFR-UHFFFAOYSA-N 0.000 description 2
- LPCWBIDEYNTTTN-UHFFFAOYSA-N n-(4-propan-2-yl-1,3-thiazol-2-yl)imidazole-1-carbothioamide Chemical compound CC(C)C1=CSC(NC(=S)N2C=NC=C2)=N1 LPCWBIDEYNTTTN-UHFFFAOYSA-N 0.000 description 2
- HJELGMRULNTAPD-UHFFFAOYSA-N n-(5-methoxy-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound COC1=NC=C2N=C(N=C(SC)SC)SC2=N1 HJELGMRULNTAPD-UHFFFAOYSA-N 0.000 description 2
- NBUYLEPFONRQCZ-UHFFFAOYSA-N n-(5-phenyl-1,3-thiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound O1C2(C3CCN(CC3)C2)CN=C1NC(S1)=NC=C1C1=CC=CC=C1 NBUYLEPFONRQCZ-UHFFFAOYSA-N 0.000 description 2
- DUZMBBAWLGCEQE-UHFFFAOYSA-N n-(6-chloropyrimidin-4-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound CSC(SC)=NC1=CC(Cl)=NC=N1 DUZMBBAWLGCEQE-UHFFFAOYSA-N 0.000 description 2
- RYFJHYNEJKFKIE-UHFFFAOYSA-N n-(6-ethoxy-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound S1C2=CC(OCC)=CC=C2N=C1NC(=S)N1C=CN=C1 RYFJHYNEJKFKIE-UHFFFAOYSA-N 0.000 description 2
- FQXJYXQXFVMXOQ-UHFFFAOYSA-N n-(6-methoxy-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound S1C2=CC(OC)=CC=C2N=C1NC(=S)N1C=CN=C1 FQXJYXQXFVMXOQ-UHFFFAOYSA-N 0.000 description 2
- KIDXXFXVPLATJJ-UHFFFAOYSA-N n-(6-methoxy-1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C1(O1)CN=C1NC1=NC2=CC=C(OC)C=C2S1 KIDXXFXVPLATJJ-UHFFFAOYSA-N 0.000 description 2
- AJVYWPXCDQCOEU-UHFFFAOYSA-N n-(6-methyl-1,3-benzothiazol-2-yl)imidazole-1-carbothioamide Chemical compound S1C2=CC(C)=CC=C2N=C1NC(=S)N1C=CN=C1 AJVYWPXCDQCOEU-UHFFFAOYSA-N 0.000 description 2
- IWZSFFYAXNHSIT-UHFFFAOYSA-N n-(7-methoxy-5-methyl-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound COC1=NC(C)=NC2=C1N=C(N=C(SC)SC)S2 IWZSFFYAXNHSIT-UHFFFAOYSA-N 0.000 description 2
- YJZQFLXZZGZDKK-UHFFFAOYSA-N n-[(2,4-dimethoxyphenyl)methyl]-6-methoxyquinoxalin-2-amine Chemical compound COC1=CC(OC)=CC=C1CNC1=CN=C(C=C(OC)C=C2)C2=N1 YJZQFLXZZGZDKK-UHFFFAOYSA-N 0.000 description 2
- CBUFXFPZRODFOI-UHFFFAOYSA-N n-[(2,4-dimethoxyphenyl)methyl]-6-methylquinoxalin-2-amine Chemical compound COC1=CC(OC)=CC=C1CNC1=CN=C(C=C(C)C=C2)C2=N1 CBUFXFPZRODFOI-UHFFFAOYSA-N 0.000 description 2
- LRAMDZDYWGJMGU-UHFFFAOYSA-N n-[2-(imidazole-1-carbothioylamino)-1,3-benzothiazol-6-yl]acetamide Chemical compound S1C2=CC(NC(=O)C)=CC=C2N=C1NC(=S)N1C=CN=C1 LRAMDZDYWGJMGU-UHFFFAOYSA-N 0.000 description 2
- WWBYXUSUDJVAED-UHFFFAOYSA-N n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=CC(OC)=CC=C1C1=CSC(NC=2OC3(C4CCN(CC4)C3)CN=2)=N1 WWBYXUSUDJVAED-UHFFFAOYSA-N 0.000 description 2
- OESGJWFGVHFAAE-UHFFFAOYSA-N n-[4-(4-methoxyphenyl)-5-methyl-1,3-thiazol-2-yl]imidazole-1-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C)SC(NC(=O)N2C=NC=C2)=N1 OESGJWFGVHFAAE-UHFFFAOYSA-N 0.000 description 2
- LZNSBKRVTSLHIE-UHFFFAOYSA-N n-[5-(4-methoxyphenyl)-1,3-thiazol-2-yl]imidazole-1-carbothioamide Chemical compound C1=CC(OC)=CC=C1C(S1)=CN=C1NC(=S)N1C=NC=C1 LZNSBKRVTSLHIE-UHFFFAOYSA-N 0.000 description 2
- KYMBMYMZVKUDDV-UHFFFAOYSA-N n-[6-[tert-butyl(dimethyl)silyl]oxy-1,3-benzothiazol-2-yl]imidazole-1-carbothioamide Chemical compound S1C2=CC(O[Si](C)(C)C(C)(C)C)=CC=C2N=C1NC(=S)N1C=CN=C1 KYMBMYMZVKUDDV-UHFFFAOYSA-N 0.000 description 2
- KEEAZYDQOLFVOL-UHFFFAOYSA-N n-pyridin-3-ylspiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound O1C2(C3CCN(CC3)C2)CN\C1=N/C1=CC=CN=C1 KEEAZYDQOLFVOL-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 2
- IHJWFFDXQRAIJG-UHFFFAOYSA-N pyridin-2-yl carbamodithioate Chemical compound C(N)(SC1=NC=CC=C1)=S IHJWFFDXQRAIJG-UHFFFAOYSA-N 0.000 description 2
- YMOMJFIZRVMXRN-UHFFFAOYSA-N pyridin-3-yl carbamodithioate Chemical compound C(N)(SC=1C=NC=CC1)=S YMOMJFIZRVMXRN-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 Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- DNACGYGXUFTEHO-UHFFFAOYSA-N pyrimidine-2,5-diamine Chemical compound NC1=CN=C(N)N=C1 DNACGYGXUFTEHO-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical group N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical class C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- CBNWMAMNZGMMAU-UHFFFAOYSA-N spiro[1-azabicyclo[2.2.2]octane-3,4'-5h-1,3-oxazole]-2'-amine Chemical compound C1OC(N)=NC21C(CC1)CCN1C2 CBNWMAMNZGMMAU-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VJBULGFITURQHJ-UHFFFAOYSA-N tert-butyl n-[6-(pyrrolidine-1-carbonyl)-1,3-benzothiazol-2-yl]carbamate Chemical compound C1=C2SC(NC(=O)OC(C)(C)C)=NC2=CC=C1C(=O)N1CCCC1 VJBULGFITURQHJ-UHFFFAOYSA-N 0.000 description 2
- 150000003585 thioureas Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
- GBSUVYGVEQDZPG-UHFFFAOYSA-N (2,4-dimethylphenyl)methanamine Chemical compound CC1=CC=C(CN)C(C)=C1 GBSUVYGVEQDZPG-UHFFFAOYSA-N 0.000 description 1
- NVOLYUXUHWBCRJ-UHFFFAOYSA-N (2-methoxypyridin-3-yl)boronic acid Chemical compound COC1=NC=CC=C1B(O)O NVOLYUXUHWBCRJ-UHFFFAOYSA-N 0.000 description 1
- YPWAJLGHACDYQS-UHFFFAOYSA-N (2-methoxypyrimidin-5-yl)boronic acid Chemical compound COC1=NC=C(B(O)O)C=N1 YPWAJLGHACDYQS-UHFFFAOYSA-N 0.000 description 1
- BSVHTRRLCAVQCZ-JDEXMCKMSA-N (2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrro Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 BSVHTRRLCAVQCZ-JDEXMCKMSA-N 0.000 description 1
- IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 1
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- AVLCTLDGDXTCNZ-FQEVSTJZSA-N (3r)-n-(2-phenylpyridin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(C=1)=CC=NC=1C1=CC=CC=C1 AVLCTLDGDXTCNZ-FQEVSTJZSA-N 0.000 description 1
- XXCHCVVLHLOEDV-AWEZNQCLSA-N (3r)-n-(4,5-dichloropyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=C(Cl)C(Cl)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 XXCHCVVLHLOEDV-AWEZNQCLSA-N 0.000 description 1
- PHBGLPXGVKDHGS-SFHVURJKSA-N (3r)-n-(5,6-dichloroisoquinolin-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=CC2=C(Cl)C(Cl)=CC=C2C=N1 PHBGLPXGVKDHGS-SFHVURJKSA-N 0.000 description 1
- KHQUNFNAMOIACW-AWEZNQCLSA-N (3r)-n-(5,6-dichloropyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound N1=C(Cl)C(Cl)=CC=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 KHQUNFNAMOIACW-AWEZNQCLSA-N 0.000 description 1
- USOMYWQXRPHQQC-SFHVURJKSA-N (3r)-n-(5-bromo-4-pyridin-3-ylpyrimidin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound BrC1=CN=C(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)N=C1C1=CC=CN=C1 USOMYWQXRPHQQC-SFHVURJKSA-N 0.000 description 1
- KRNABMMFSKMSJJ-INIZCTEOSA-N (3r)-n-(5-chloro-1,3-benzoxazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC(Cl)=CC=C2O1 KRNABMMFSKMSJJ-INIZCTEOSA-N 0.000 description 1
- NLSADPPBWBUTDK-HNNXBMFYSA-N (3r)-n-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC=C(Cl)N=C2S1 NLSADPPBWBUTDK-HNNXBMFYSA-N 0.000 description 1
- JORBPZWZVPZZKU-SFHVURJKSA-N (3r)-n-(5-cyclopentyloxypyrimidin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1CCCC1OC(C=N1)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 JORBPZWZVPZZKU-SFHVURJKSA-N 0.000 description 1
- QBDRIJRFLYTRHO-ZDUSSCGKSA-N (3r)-n-(5-ethyl-1,3,4-oxadiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound O1C(CC)=NN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 QBDRIJRFLYTRHO-ZDUSSCGKSA-N 0.000 description 1
- LLSDHTXRWBJQEM-LBPRGKRZSA-N (3r)-n-(5-methyl-1,3,4-oxadiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound O1C(C)=NN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 LLSDHTXRWBJQEM-LBPRGKRZSA-N 0.000 description 1
- FTBWMNKCUZZEKB-FQEVSTJZSA-N (3r)-n-(5-phenylpyridin-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(C=1)=CN=CC=1C1=CC=CC=C1 FTBWMNKCUZZEKB-FQEVSTJZSA-N 0.000 description 1
- JEIHYUJKPUPKOT-AWEZNQCLSA-N (3r)-n-(6-bromo-[1,3]thiazolo[4,5-b]pyrazin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=NC=C(Br)N=C2S1 JEIHYUJKPUPKOT-AWEZNQCLSA-N 0.000 description 1
- SPSBIAARVKFBRI-ZDUSSCGKSA-N (3r)-n-(6-bromopyridazin-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound N1=NC(Br)=CC=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 SPSBIAARVKFBRI-ZDUSSCGKSA-N 0.000 description 1
- RHTUMZMNPADJLE-AWEZNQCLSA-N (3r)-n-(6-chloropyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound ClC1=CC=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=N1 RHTUMZMNPADJLE-AWEZNQCLSA-N 0.000 description 1
- MMPRRMIZZMKFAF-SFHVURJKSA-N (3r)-n-(6-cyclopentyloxypyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1CCCC1OC1=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=NC=N1 MMPRRMIZZMKFAF-SFHVURJKSA-N 0.000 description 1
- ARRIQLFAOHIHOY-INIZCTEOSA-N (3r)-n-(6-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NN(C=C(OC)C=C2)C2=N1 ARRIQLFAOHIHOY-INIZCTEOSA-N 0.000 description 1
- CZLTXTIEEPGFOS-SFHVURJKSA-N (3r)-n-(6-methoxyquinoxalin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC=C(OC)C=C2N=C1 CZLTXTIEEPGFOS-SFHVURJKSA-N 0.000 description 1
- BTWBGYYGCASTRI-QHCPKHFHSA-N (3r)-n-(6-naphthalen-2-ylpyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]21OC(NC=1N=CN=C(C=1)C=1C=C3C=CC=CC3=CC=1)=NC2 BTWBGYYGCASTRI-QHCPKHFHSA-N 0.000 description 1
- NTZKNOCUCKBRFH-IBGZPJMESA-N (3r)-n-(6-phenoxypyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(N=CN=1)=CC=1OC1=CC=CC=C1 NTZKNOCUCKBRFH-IBGZPJMESA-N 0.000 description 1
- YUSCNUFLONHFOI-FQEVSTJZSA-N (3r)-n-(6-phenylpyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(N=1)=CC=CC=1C1=CC=CC=C1 YUSCNUFLONHFOI-FQEVSTJZSA-N 0.000 description 1
- WVNOFRZQUMORMI-IBGZPJMESA-N (3r)-n-(6-phenylpyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(N=CN=1)=CC=1C1=CC=CC=C1 WVNOFRZQUMORMI-IBGZPJMESA-N 0.000 description 1
- IYKYOSGGIVUSNM-SFHVURJKSA-N (3r)-n-(6-pyridin-3-ylpyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(N=CN=1)=CC=1C1=CC=CN=C1 IYKYOSGGIVUSNM-SFHVURJKSA-N 0.000 description 1
- OEBYXCLQXOTPJE-SFHVURJKSA-N (3r)-n-(6-pyridin-4-ylpyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C([C@]1(C2CCN(CC2)C1)O1)N=C1NC(N=CN=1)=CC=1C1=CC=NC=C1 OEBYXCLQXOTPJE-SFHVURJKSA-N 0.000 description 1
- KZQPGEKJMLCKJN-SFHVURJKSA-N (3r)-n-(7-methylquinoxalin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC(C)=CC=C2N=C1 KZQPGEKJMLCKJN-SFHVURJKSA-N 0.000 description 1
- KRKCUYONLACVIN-AWEZNQCLSA-N (3r)-n-([1,3]thiazolo[4,5-b]pyrazin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]21OC(NC=1SC3=NC=CN=C3N=1)=NC2 KRKCUYONLACVIN-AWEZNQCLSA-N 0.000 description 1
- WMHGQZFNZDLVRU-HNNXBMFYSA-N (3r)-n-([1,3]thiazolo[5,4-b]pyridin-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]21OC(NC=1SC3=NC=CC=C3N=1)=NC2 WMHGQZFNZDLVRU-HNNXBMFYSA-N 0.000 description 1
- FTZDQURZBJNTLV-IBGZPJMESA-N (3r)-n-[5-(6-methoxypyridin-3-yl)pyrazin-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=NC(OC)=CC=C1C(N=C1)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 FTZDQURZBJNTLV-IBGZPJMESA-N 0.000 description 1
- XEHLPXIKSPZCIB-INIZCTEOSA-N (3r)-n-[5-(difluoromethoxy)-[1,3]thiazolo[5,4-b]pyridin-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC=C(OC(F)F)N=C2S1 XEHLPXIKSPZCIB-INIZCTEOSA-N 0.000 description 1
- JDVSSCUYTGNWQT-AWEZNQCLSA-N (3r)-n-[5-(difluoromethoxy)pyrimidin-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound N1=CC(OC(F)F)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 JDVSSCUYTGNWQT-AWEZNQCLSA-N 0.000 description 1
- YFJQVJATGSDKAJ-IBGZPJMESA-N (3r)-n-[6-(3-chlorophenyl)pyrimidin-4-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound ClC1=CC=CC(C=2N=CN=C(NC=3O[C@@]4(C5CCN(CC5)C4)CN=3)C=2)=C1 YFJQVJATGSDKAJ-IBGZPJMESA-N 0.000 description 1
- LETXCYWPGGCZGQ-FQEVSTJZSA-N (3r)-n-[6-(4-methoxyphenyl)pyrimidin-4-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=CC(OC)=CC=C1C1=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=NC=N1 LETXCYWPGGCZGQ-FQEVSTJZSA-N 0.000 description 1
- WOJCVPHCTJFPKM-KRWDZBQOSA-N (3r)-n-[6-(difluoromethoxy)-1,3-benzothiazol-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC=C(OC(F)F)C=C2S1 WOJCVPHCTJFPKM-KRWDZBQOSA-N 0.000 description 1
- SNBBXZLFADZUSU-SFHVURJKSA-N (3r)-n-[6-(difluoromethoxy)-1-methylindazol-3-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C12=CC=C(OC(F)F)C=C2N(C)N=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 SNBBXZLFADZUSU-SFHVURJKSA-N 0.000 description 1
- IMMCHFLTBDORJH-INIZCTEOSA-N (3r)-n-furo[3,2-c]pyridin-4-ylspiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]21OC(NC=1C=3C=COC=3C=CN=1)=NC2 IMMCHFLTBDORJH-INIZCTEOSA-N 0.000 description 1
- ZDTPXUKLGIDOCS-SFHVURJKSA-N (3r)-n-isoquinolin-3-ylspiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2[C@]21OC(NC=1N=CC3=CC=CC=C3C=1)=NC2 ZDTPXUKLGIDOCS-SFHVURJKSA-N 0.000 description 1
- WWBYXUSUDJVAED-LJQANCHMSA-N (3s)-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=CC(OC)=CC=C1C1=CSC(NC=2O[C@]3(C4CCN(CC4)C3)CN=2)=N1 WWBYXUSUDJVAED-LJQANCHMSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- HMTSWYPNXFHGEP-UHFFFAOYSA-N (4-methylphenyl)methanamine Chemical compound CC1=CC=C(CN)C=C1 HMTSWYPNXFHGEP-UHFFFAOYSA-N 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
- IXZYSKNWHPRGKV-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-n-([1,3]oxazolo[4,5-b]pyridin-2-yl)methanimine Chemical compound C1=CC=C2OC(N=C(SC)SC)=NC2=N1 IXZYSKNWHPRGKV-UHFFFAOYSA-N 0.000 description 1
- KZGYCTBSZHPCAQ-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-n-([1,3]thiazolo[5,4-b]pyridin-2-yl)methanimine Chemical compound C1=CN=C2SC(N=C(SC)SC)=NC2=C1 KZGYCTBSZHPCAQ-UHFFFAOYSA-N 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical group C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical group C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- ORIIXCOYEOIFSN-UHFFFAOYSA-N 1,3-benzothiazol-6-ol Chemical compound OC1=CC=C2N=CSC2=C1 ORIIXCOYEOIFSN-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical group C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- FNLYFJIEFIZBFC-UHFFFAOYSA-N 1,6-naphthyridin-2-amine Chemical compound C1=NC=CC2=NC(N)=CC=C21 FNLYFJIEFIZBFC-UHFFFAOYSA-N 0.000 description 1
- OKGNEHOXHXVIMK-KRWDZBQOSA-N 1-[5-[[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-yl]amino]pyrazin-2-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C(N=C1)=CN=C1NC(O1)=NC[C@]11C(CC2)CCN2C1 OKGNEHOXHXVIMK-KRWDZBQOSA-N 0.000 description 1
- ZKMZPXWMMSBLNO-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-one Chemical compound C1CC2C(=O)CN1CC2 ZKMZPXWMMSBLNO-UHFFFAOYSA-N 0.000 description 1
- MNBAABZKRCNMAP-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octane;4,5-dihydro-1,3-oxazole Chemical class C1CN=CO1.C1CC2CCN1CC2 MNBAABZKRCNMAP-UHFFFAOYSA-N 0.000 description 1
- XDFZKQJLNGNJAN-UHFFFAOYSA-N 1-methylbenzimidazol-2-amine Chemical compound C1=CC=C2N(C)C(N)=NC2=C1 XDFZKQJLNGNJAN-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- VYDQUABHDFWIIX-UHFFFAOYSA-N 2,2-difluoro-2-fluorosulfonylacetic acid Chemical compound OC(=O)C(F)(F)S(F)(=O)=O VYDQUABHDFWIIX-UHFFFAOYSA-N 0.000 description 1
- ALUQMCBDQKDRAK-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazole Chemical compound C1C=CC=C2SCNC21 ALUQMCBDQKDRAK-UHFFFAOYSA-N 0.000 description 1
- MFJBJIDWQXSZHR-UHFFFAOYSA-N 2,3-dichloro-6-isothiocyanatopyridine Chemical compound ClC1=CC=C(N=C=S)N=C1Cl MFJBJIDWQXSZHR-UHFFFAOYSA-N 0.000 description 1
- RINHVELYMZLXIW-UHFFFAOYSA-N 2,4-dichloropyrimidin-5-amine Chemical compound NC1=CN=C(Cl)N=C1Cl RINHVELYMZLXIW-UHFFFAOYSA-N 0.000 description 1
- LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 1
- DAMKLTBYCMQBPW-KRWDZBQOSA-N 2,4-dimethyl-6-[[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-yl]amino]pyridine-3-carbonitrile Chemical compound CC1=C(C#N)C(C)=CC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=N1 DAMKLTBYCMQBPW-KRWDZBQOSA-N 0.000 description 1
- RTTWPZSZAYCRKF-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxy)pyrimidin-4-amine Chemical compound NC1=CC=NC(OCC(F)(F)F)=N1 RTTWPZSZAYCRKF-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- HMAATCOHUYHORT-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-benzothiazole-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2SC(NC(=O)OC(C)(C)C)=NC2=C1 HMAATCOHUYHORT-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- UDLFPPHYXDHXCU-INIZCTEOSA-N 2-[[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-yl]amino]-1,3-benzothiazol-6-ol Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC2=CC=C(O)C=C2S1 UDLFPPHYXDHXCU-INIZCTEOSA-N 0.000 description 1
- VEAWPMXEROMSKF-HNNXBMFYSA-N 2-[[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-yl]amino]-4h-[1,3]thiazolo[5,4-b]pyridin-5-one Chemical compound C1N(CC2)CCC2[C@]1(O1)CN=C1NC1=NC(C=CC(N2)=O)=C2S1 VEAWPMXEROMSKF-HNNXBMFYSA-N 0.000 description 1
- YJOBZEMOBFJWDV-UHFFFAOYSA-N 2-[bis(methylsulfanyl)methylideneamino]-n,n-dimethyl-[1,3]thiazolo[5,4-d]pyrimidin-5-amine Chemical compound N1=C(N(C)C)N=C2SC(N=C(SC)SC)=NC2=C1 YJOBZEMOBFJWDV-UHFFFAOYSA-N 0.000 description 1
- YJTBHWXNEMGNDC-UHFFFAOYSA-N 2-amino-1,3-thiazole-5-carbonitrile Chemical compound NC1=NC=C(C#N)S1 YJTBHWXNEMGNDC-UHFFFAOYSA-N 0.000 description 1
- JWYUFVNJZUSCSM-UHFFFAOYSA-N 2-aminobenzimidazole Chemical compound C1=CC=C2NC(N)=NC2=C1 JWYUFVNJZUSCSM-UHFFFAOYSA-N 0.000 description 1
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 description 1
- BMTSZVZQNMNPCT-UHFFFAOYSA-N 2-aminopyridin-3-ol Chemical compound NC1=NC=CC=C1O BMTSZVZQNMNPCT-UHFFFAOYSA-N 0.000 description 1
- GNTGEMWEXKBWBX-UHFFFAOYSA-N 2-bromopyridin-4-amine Chemical compound NC1=CC=NC(Br)=C1 GNTGEMWEXKBWBX-UHFFFAOYSA-N 0.000 description 1
- AOZNIFQUCUSYLD-UHFFFAOYSA-N 2-chloro-4-propan-2-ylpyrimidine Chemical compound CC(C)C1=CC=NC(Cl)=N1 AOZNIFQUCUSYLD-UHFFFAOYSA-N 0.000 description 1
- MDDZKKIHTFOAEF-UHFFFAOYSA-N 2-chloro-6-methylquinoxaline Chemical compound N1=C(Cl)C=NC2=CC(C)=CC=C21 MDDZKKIHTFOAEF-UHFFFAOYSA-N 0.000 description 1
- WJDJKCAURKUNNC-UHFFFAOYSA-N 2-chloro-7-methoxyquinoxaline Chemical compound N1=CC(Cl)=NC2=CC(OC)=CC=C21 WJDJKCAURKUNNC-UHFFFAOYSA-N 0.000 description 1
- XLTMISOVULFCFD-UHFFFAOYSA-N 2-chloro-7-methylquinoxaline Chemical compound N1=CC(Cl)=NC2=CC(C)=CC=C21 XLTMISOVULFCFD-UHFFFAOYSA-N 0.000 description 1
- CMKGLMUSTXZJBU-UHFFFAOYSA-N 2-isothiocyanato-6-methoxy-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=C(OC)C=CC2=NC(N=C=S)=NN21 CMKGLMUSTXZJBU-UHFFFAOYSA-N 0.000 description 1
- XUDBPGPIBCBAAW-UHFFFAOYSA-N 2-isothiocyanato-7-methylquinoxaline Chemical compound N1=CC(N=C=S)=NC2=CC(C)=CC=C21 XUDBPGPIBCBAAW-UHFFFAOYSA-N 0.000 description 1
- RHVXTBTTZKLODC-UHFFFAOYSA-N 2-methoxy-5-pyrimidin-4-ylpyrimidine Chemical compound COC1=NC=C(C=N1)C1=NC=NC=C1 RHVXTBTTZKLODC-UHFFFAOYSA-N 0.000 description 1
- RZAZBVCZBWDSBJ-INIZCTEOSA-N 2-methyl-6-[[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-yl]amino]pyridine-3-carbonitrile Chemical compound C1=C(C#N)C(C)=NC(NC=2O[C@@]3(C4CCN(CC4)C3)CN=2)=C1 RZAZBVCZBWDSBJ-INIZCTEOSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 1
- HEPPAPZASXFWTB-UHFFFAOYSA-N 3,3-dibromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)C(Br)Br HEPPAPZASXFWTB-UHFFFAOYSA-N 0.000 description 1
- WLIWKYZJBIUWSG-UHFFFAOYSA-N 3,4-dichloropyridin-2-amine Chemical compound NC1=NC=CC(Cl)=C1Cl WLIWKYZJBIUWSG-UHFFFAOYSA-N 0.000 description 1
- OCWBGKZFOYMCCN-UHFFFAOYSA-N 3,5-dichloropyridin-2-amine Chemical compound NC1=NC=C(Cl)C=C1Cl OCWBGKZFOYMCCN-UHFFFAOYSA-N 0.000 description 1
- MESWZJXURVTILO-UHFFFAOYSA-N 3-(5-methoxy-[1,3]thiazolo[5,4-b]pyridin-2-yl)spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane] Chemical compound COC1=CC=C2C(=N1)SC(=N2)N1COC2(CN3CCC2CC3)C1 MESWZJXURVTILO-UHFFFAOYSA-N 0.000 description 1
- RZJPBQGRCNJYBU-UHFFFAOYSA-N 3-chloropyridin-2-amine Chemical compound NC1=NC=CC=C1Cl RZJPBQGRCNJYBU-UHFFFAOYSA-N 0.000 description 1
- VMSZFBSYWXMXRF-UHFFFAOYSA-N 3-isothiocyanatopyridine Chemical compound S=C=NC1=CC=CN=C1 VMSZFBSYWXMXRF-UHFFFAOYSA-N 0.000 description 1
- LGNNZKURGCOEJY-UHFFFAOYSA-N 3-methyl-1,2,4-oxadiazol-5-amine Chemical compound CC1=NOC(N)=N1 LGNNZKURGCOEJY-UHFFFAOYSA-N 0.000 description 1
- DJKUIGPCSNRFRK-UHFFFAOYSA-N 3-methyl-1,2,4-thiadiazol-5-amine Chemical compound CC1=NSC(N)=N1 DJKUIGPCSNRFRK-UHFFFAOYSA-N 0.000 description 1
- SMWAOXCEPHEGFV-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine Chemical compound C1CCCC2=C1N=C(N)S2 SMWAOXCEPHEGFV-UHFFFAOYSA-N 0.000 description 1
- CRRAQLWJVYODCL-UHFFFAOYSA-N 4,5-dichloropyridin-2-amine Chemical compound NC1=CC(Cl)=C(Cl)C=N1 CRRAQLWJVYODCL-UHFFFAOYSA-N 0.000 description 1
- FKRXXAMAHOGYNT-UHFFFAOYSA-N 4,6-dichloro-2-methylpyrimidin-5-amine Chemical compound CC1=NC(Cl)=C(N)C(Cl)=N1 FKRXXAMAHOGYNT-UHFFFAOYSA-N 0.000 description 1
- AGJMDETXSYICGZ-UHFFFAOYSA-N 4,6-dichloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC(Cl)=N1 AGJMDETXSYICGZ-UHFFFAOYSA-N 0.000 description 1
- VKXBPDWBNXTLPW-UHFFFAOYSA-N 4-(3-chlorophenyl)pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2C=C(Cl)C=CC=2)=N1 VKXBPDWBNXTLPW-UHFFFAOYSA-N 0.000 description 1
- WUTXFLYFZOMYSF-UHFFFAOYSA-N 4-(4-methoxyphenyl)-5-methyl-1,3-thiazol-2-amine Chemical compound C1=CC(OC)=CC=C1C1=C(C)SC(N)=N1 WUTXFLYFZOMYSF-UHFFFAOYSA-N 0.000 description 1
- OERIHGQAGTVWPN-UHFFFAOYSA-N 4-(difluoromethoxy)-2-fluorobenzonitrile Chemical compound FC(F)OC1=CC=C(C#N)C(F)=C1 OERIHGQAGTVWPN-UHFFFAOYSA-N 0.000 description 1
- NDEZTSHWEPQVBX-UHFFFAOYSA-N 4-(difluoromethoxy)aniline Chemical compound NC1=CC=C(OC(F)F)C=C1 NDEZTSHWEPQVBX-UHFFFAOYSA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 1
- OEQQFQXMCPMEIH-UHFFFAOYSA-N 4-chloro-1,3-benzothiazol-2-amine Chemical compound C1=CC=C2SC(N)=NC2=C1Cl OEQQFQXMCPMEIH-UHFFFAOYSA-N 0.000 description 1
- RRMVDLLCVGZDMH-UHFFFAOYSA-N 4-chloro-5,6-dimethylpyrimidin-2-amine Chemical compound CC1=NC(N)=NC(Cl)=C1C RRMVDLLCVGZDMH-UHFFFAOYSA-N 0.000 description 1
- OPFFYLJLHPZSEO-UHFFFAOYSA-N 4-chlorofuro[3,2-c]pyridine Chemical compound ClC1=NC=CC2=C1C=CO2 OPFFYLJLHPZSEO-UHFFFAOYSA-N 0.000 description 1
- FNIJWHCOQRZMIO-UHFFFAOYSA-N 4-cyclopentyloxypyrimidin-2-amine Chemical compound NC1=NC=CC(OC2CCCC2)=N1 FNIJWHCOQRZMIO-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- MFDBYMJQLWCZKY-UHFFFAOYSA-N 4-isothiocyanato-6-(2-methoxypyrimidin-5-yl)pyrimidine Chemical compound C1=NC(OC)=NC=C1C1=CC(N=C=S)=NC=N1 MFDBYMJQLWCZKY-UHFFFAOYSA-N 0.000 description 1
- AGAHETWGCFCMDK-UHFFFAOYSA-N 4-methoxybenzene-1,2-diamine Chemical compound COC1=CC=C(N)C(N)=C1 AGAHETWGCFCMDK-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- GRIATXVEXOFBGO-UHFFFAOYSA-N 4-methyl-1,3-benzothiazol-2-amine Chemical compound CC1=CC=CC2=C1N=C(N)S2 GRIATXVEXOFBGO-UHFFFAOYSA-N 0.000 description 1
- SJISCEAZUHNOMD-UHFFFAOYSA-N 4-phenylcyclohexan-1-amine Chemical compound C1CC(N)CCC1C1=CC=CC=C1 SJISCEAZUHNOMD-UHFFFAOYSA-N 0.000 description 1
- LGPVXXJBWWYOSL-UHFFFAOYSA-N 4-propan-2-yl-1,3-thiazol-2-amine Chemical compound CC(C)C1=CSC(N)=N1 LGPVXXJBWWYOSL-UHFFFAOYSA-N 0.000 description 1
- MLNFMFAMNBGAQT-UHFFFAOYSA-N 4-propan-2-yloxyaniline Chemical compound CC(C)OC1=CC=C(N)C=C1 MLNFMFAMNBGAQT-UHFFFAOYSA-N 0.000 description 1
- LQHQKYWYKPLKCH-UHFFFAOYSA-N 4-pyridin-3-ylpyrimidin-2-amine Chemical compound NC1=NC=CC(C=2C=NC=CC=2)=N1 LQHQKYWYKPLKCH-UHFFFAOYSA-N 0.000 description 1
- MPGDXNFGLHUWKH-UHFFFAOYSA-N 4h-[1,3]thiazolo[5,4-b]pyridin-5-one Chemical compound N1C(=O)C=CC2=C1SC=N2 MPGDXNFGLHUWKH-UHFFFAOYSA-N 0.000 description 1
- PWRHKLKFADDKHS-UHFFFAOYSA-N 5,6-diamino-1h-pyrimidin-4-one Chemical compound NC=1NC=NC(=O)C=1N PWRHKLKFADDKHS-UHFFFAOYSA-N 0.000 description 1
- VKULPGMHEHWFFN-UHFFFAOYSA-N 5,7-dichloroisoquinolin-1-amine Chemical compound C1=C(Cl)C=C2C(N)=NC=CC2=C1Cl VKULPGMHEHWFFN-UHFFFAOYSA-N 0.000 description 1
- MVRGZAICFHFZIJ-UHFFFAOYSA-N 5-(4-methoxyphenyl)-1,3-thiazol-2-amine Chemical compound C1=CC(OC)=CC=C1C1=CN=C(N)S1 MVRGZAICFHFZIJ-UHFFFAOYSA-N 0.000 description 1
- ZRZKHMJBGSDIMH-UHFFFAOYSA-N 5-bromo-3-isothiocyanatoisoquinoline Chemical compound N1=C(N=C=S)C=C2C(Br)=CC=CC2=C1 ZRZKHMJBGSDIMH-UHFFFAOYSA-N 0.000 description 1
- VZWSVFLRMXYQLA-UHFFFAOYSA-N 5-bromoisoquinolin-3-amine Chemical compound C1=CC=C2C=NC(N)=CC2=C1Br VZWSVFLRMXYQLA-UHFFFAOYSA-N 0.000 description 1
- MDQXGHBCDCOOSM-UHFFFAOYSA-N 5-bromopyridin-3-amine Chemical compound NC1=CN=CC(Br)=C1 MDQXGHBCDCOOSM-UHFFFAOYSA-N 0.000 description 1
- FPUPPVDVOFJSEP-UHFFFAOYSA-N 5-chloro-3-fluoropyridin-2-amine Chemical compound NC1=NC=C(Cl)C=C1F FPUPPVDVOFJSEP-UHFFFAOYSA-N 0.000 description 1
- DGRCJSWXMGENMG-UHFFFAOYSA-N 5-chloro-4-methylpyridin-2-amine Chemical compound CC1=CC(N)=NC=C1Cl DGRCJSWXMGENMG-UHFFFAOYSA-N 0.000 description 1
- WCCLUBJCLSIZOC-UHFFFAOYSA-N 5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound C1=C(Cl)N=C2SC(N)=NC2=C1 WCCLUBJCLSIZOC-UHFFFAOYSA-N 0.000 description 1
- XHSTYRIUVMKGDX-UHFFFAOYSA-N 5-ethyl-1,3,4-oxadiazol-2-amine Chemical compound CCC1=NN=C(N)O1 XHSTYRIUVMKGDX-UHFFFAOYSA-N 0.000 description 1
- XPXWYVCQCNFIIJ-UHFFFAOYSA-N 5-methyl-1,3,4-oxadiazol-2-amine Chemical compound CC1=NN=C(N)O1 XPXWYVCQCNFIIJ-UHFFFAOYSA-N 0.000 description 1
- UQYIJTRKEBHOPX-UHFFFAOYSA-N 5-n,5-n-dimethyl-[1,3]thiazolo[5,4-d]pyrimidine-2,5-diamine Chemical compound CN(C)C1=NC=C2N=C(N)SC2=N1 UQYIJTRKEBHOPX-UHFFFAOYSA-N 0.000 description 1
- XKWSQIMYNVLGBO-UHFFFAOYSA-N 5-nitro-1h-pyridin-2-one Chemical compound OC1=CC=C([N+]([O-])=O)C=N1 XKWSQIMYNVLGBO-UHFFFAOYSA-N 0.000 description 1
- LSLUWQIENURREM-UHFFFAOYSA-N 5-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC=C1C1=CC=CC=C1 LSLUWQIENURREM-UHFFFAOYSA-N 0.000 description 1
- LXRKXJMZWGBMOV-UHFFFAOYSA-N 6,7-dichloroisoquinolin-1-amine Chemical compound ClC1=C(Cl)C=C2C(N)=NC=CC2=C1 LXRKXJMZWGBMOV-UHFFFAOYSA-N 0.000 description 1
- AJWURYOLKGMWBS-UHFFFAOYSA-N 6-(2-methoxypyrimidin-5-yl)pyrimidin-4-amine Chemical compound C1=NC(OC)=NC=C1C1=CC(N)=NC=N1 AJWURYOLKGMWBS-UHFFFAOYSA-N 0.000 description 1
- JHQJTIIYVDDSEN-UHFFFAOYSA-N 6-[tert-butyl(dimethyl)silyl]oxy-1,3-benzothiazol-2-amine Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C2N=C(N)SC2=C1 JHQJTIIYVDDSEN-UHFFFAOYSA-N 0.000 description 1
- ZFXMWBGQRGABCI-UHFFFAOYSA-N 6-amino-2,4-dimethylpyridine-3-carbonitrile Chemical compound CC1=CC(N)=NC(C)=C1C#N ZFXMWBGQRGABCI-UHFFFAOYSA-N 0.000 description 1
- OZAIJUZOQOBQDW-UHFFFAOYSA-N 6-amino-2-methylpyridine-3-carbonitrile Chemical compound CC1=NC(N)=CC=C1C#N OZAIJUZOQOBQDW-UHFFFAOYSA-N 0.000 description 1
- XYAFECHDSIQGHU-UHFFFAOYSA-N 6-bromo-[1,3]thiazolo[4,5-b]pyrazin-2-amine Chemical compound C1=C(Br)N=C2SC(N)=NC2=N1 XYAFECHDSIQGHU-UHFFFAOYSA-N 0.000 description 1
- VMNXKIDUTPOHPO-UHFFFAOYSA-N 6-chloro-1,3-benzothiazol-2-amine Chemical compound C1=C(Cl)C=C2SC(N)=NC2=C1 VMNXKIDUTPOHPO-UHFFFAOYSA-N 0.000 description 1
- OBYJTLDIQBWBHM-UHFFFAOYSA-N 6-chloropyridin-2-amine Chemical compound NC1=CC=CC(Cl)=N1 OBYJTLDIQBWBHM-UHFFFAOYSA-N 0.000 description 1
- KOYJWFGMEBETBU-UHFFFAOYSA-N 6-ethoxy-1,3-benzothiazol-2-amine Chemical compound CCOC1=CC=C2N=C(N)SC2=C1 KOYJWFGMEBETBU-UHFFFAOYSA-N 0.000 description 1
- KZHGPDSVHSDCMX-UHFFFAOYSA-N 6-methoxy-1,3-benzothiazol-2-amine Chemical compound COC1=CC=C2N=C(N)SC2=C1 KZHGPDSVHSDCMX-UHFFFAOYSA-N 0.000 description 1
- UUVDJIWRSIJEBS-UHFFFAOYSA-N 6-methoxypyridin-3-amine Chemical compound COC1=CC=C(N)C=N1 UUVDJIWRSIJEBS-UHFFFAOYSA-N 0.000 description 1
- VELRBZDRGTVGGT-UHFFFAOYSA-N 6-methoxypyrimidin-4-amine Chemical compound COC1=CC(N)=NC=N1 VELRBZDRGTVGGT-UHFFFAOYSA-N 0.000 description 1
- YUGIDNINXCKSJH-UHFFFAOYSA-N 6-methoxyquinoxalin-2-amine Chemical compound N1=C(N)C=NC2=CC(OC)=CC=C21 YUGIDNINXCKSJH-UHFFFAOYSA-N 0.000 description 1
- DZWTXWPRWRLHIL-UHFFFAOYSA-N 6-methyl-1,3-benzothiazol-2-amine Chemical compound CC1=CC=C2N=C(N)SC2=C1 DZWTXWPRWRLHIL-UHFFFAOYSA-N 0.000 description 1
- CDCFXBSOKSIQPU-UHFFFAOYSA-N 6-phenylmethoxypyridin-3-amine Chemical compound N1=CC(N)=CC=C1OCC1=CC=CC=C1 CDCFXBSOKSIQPU-UHFFFAOYSA-N 0.000 description 1
- YGCJBESZJIGDMP-UHFFFAOYSA-N 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound NC1=NC=NN2C(Br)=CC=C12 YGCJBESZJIGDMP-UHFFFAOYSA-N 0.000 description 1
- QPKYPGWRTFUFOU-UHFFFAOYSA-N 7-methoxy-[1,3]thiazolo[5,4-d]pyrimidin-2-amine Chemical compound COC1=NC=NC2=C1N=C(N)S2 QPKYPGWRTFUFOU-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 101710195183 Alpha-bungarotoxin Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 208000007415 Anhedonia Diseases 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- MEVYQHZARTXYOB-UHFFFAOYSA-N C1=CC=C2C(=C1)N=C(O2)SC(=S)N Chemical compound C1=CC=C2C(=C1)N=C(O2)SC(=S)N MEVYQHZARTXYOB-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 206010012289 Dementia 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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033864 Paranoia Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- 108010077495 Peptide oostatic hormone Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010041243 Social avoidant behaviour Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- YGCODSQDUUUKIV-UHFFFAOYSA-N Zoxazolamine Chemical compound ClC1=CC=C2OC(N)=NC2=C1 YGCODSQDUUUKIV-UHFFFAOYSA-N 0.000 description 1
- DACWQSNZECJJGG-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine Chemical group C1=CC=CN2N=CN=C21 DACWQSNZECJJGG-UHFFFAOYSA-N 0.000 description 1
- VTIVYUBSVCXRPI-UHFFFAOYSA-N [1,2]thiazolo[5,4-b]pyridine Chemical group C1=CC=C2C=NSC2=N1 VTIVYUBSVCXRPI-UHFFFAOYSA-N 0.000 description 1
- OGWPHTRWLWDCOC-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound C1=CN=C2SC(N)=NC2=C1 OGWPHTRWLWDCOC-UHFFFAOYSA-N 0.000 description 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 1
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical compound C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 1
- JBIDUFGTLLGTBI-UHFFFAOYSA-N bis(methylsulfanyl)methanimine Chemical class CSC(=N)SC JBIDUFGTLLGTBI-UHFFFAOYSA-N 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002038 chemiluminescence detection Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- NDTCXABJQNJPCF-UHFFFAOYSA-N chlorocyclopentane Chemical compound ClC1CCCC1 NDTCXABJQNJPCF-UHFFFAOYSA-N 0.000 description 1
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 description 1
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 208000019014 inability to feed Diseases 0.000 description 1
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical group C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- VYCKDIRCVDCQAE-UHFFFAOYSA-N isoquinolin-3-amine Chemical compound C1=CC=C2C=NC(N)=CC2=C1 VYCKDIRCVDCQAE-UHFFFAOYSA-N 0.000 description 1
- 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 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
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- QGBPKJFJAVDUNC-UHFFFAOYSA-N methyl 4-methoxy-3-oxobutanoate Chemical compound COCC(=O)CC(=O)OC QGBPKJFJAVDUNC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- INXMNHNLPLWABV-UHFFFAOYSA-N n'-[(4-bromophenyl)methyl]-2,2-diethoxyethanimidamide Chemical compound CCOC(OCC)C(=N)NCC1=CC=C(Br)C=C1 INXMNHNLPLWABV-UHFFFAOYSA-N 0.000 description 1
- NASVTBDJHWPMOO-UHFFFAOYSA-N n,n'-dimethylmethanediimine Chemical compound CN=C=NC NASVTBDJHWPMOO-UHFFFAOYSA-N 0.000 description 1
- VUSUESCSIUWQMT-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C21OC(NC=1SC3=CC=CC=C3N=1)=NC2 VUSUESCSIUWQMT-UHFFFAOYSA-N 0.000 description 1
- PEVWFQQFUKFJFK-UHFFFAOYSA-N n-(1,3-benzoxazol-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound C1=CC=C2OC(N=C(SC)SC)=NC2=C1 PEVWFQQFUKFJFK-UHFFFAOYSA-N 0.000 description 1
- BRSUAKMKDAAYJX-UHFFFAOYSA-N n-(2-amino-1,3-benzothiazol-6-yl)acetamide Chemical compound CC(=O)NC1=CC=C2N=C(N)SC2=C1 BRSUAKMKDAAYJX-UHFFFAOYSA-N 0.000 description 1
- MDSDFKBIYXYXNF-UHFFFAOYSA-N n-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C21OC(NC=1SC=3CCCCC=3N=1)=NC2 MDSDFKBIYXYXNF-UHFFFAOYSA-N 0.000 description 1
- OMNHZKWWQQBAMJ-UHFFFAOYSA-N n-(4-chloro-1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C1(O1)CN=C1NC(S1)=NC2=C1C=CC=C2Cl OMNHZKWWQQBAMJ-UHFFFAOYSA-N 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- OXMVTMRZGPMPEJ-UHFFFAOYSA-N n-(4-methyl-1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C1(O1)CN=C1NC(S1)=NC2=C1C=CC=C2C OXMVTMRZGPMPEJ-UHFFFAOYSA-N 0.000 description 1
- FUCCVTKQLLOEPO-UHFFFAOYSA-N n-(5-methoxy-[1,3]thiazolo[5,4-b]pyridin-2-yl)imidazole-1-carbothioamide Chemical compound S1C2=NC(OC)=CC=C2N=C1NC(=S)N1C=CN=C1 FUCCVTKQLLOEPO-UHFFFAOYSA-N 0.000 description 1
- WDINSPOQKMZCHQ-UHFFFAOYSA-N n-(5-phenyl-1,3-thiazol-2-yl)imidazole-1-carbothioamide Chemical compound C1=CN=CN1C(=S)NC(S1)=NC=C1C1=CC=CC=C1 WDINSPOQKMZCHQ-UHFFFAOYSA-N 0.000 description 1
- JFPMKTAXLLHMRR-UHFFFAOYSA-N n-(6-chloro-1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C1(O1)CN=C1NC1=NC2=CC=C(Cl)C=C2S1 JFPMKTAXLLHMRR-UHFFFAOYSA-N 0.000 description 1
- YPWKLBCTOUEZKE-UHFFFAOYSA-N n-(6-chloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC(Cl)=N1 YPWKLBCTOUEZKE-UHFFFAOYSA-N 0.000 description 1
- DYYIGENAVULQMH-UHFFFAOYSA-N n-(6-ethoxy-1,3-benzothiazol-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1N(CC2)CCC2C1(O1)CN=C1NC1=NC2=CC=C(OCC)C=C2S1 DYYIGENAVULQMH-UHFFFAOYSA-N 0.000 description 1
- HUBRSUQLBOOYKF-UHFFFAOYSA-N n-(7-methoxy-[1,3]thiazolo[5,4-d]pyrimidin-2-yl)-1,1-bis(methylsulfanyl)methanimine Chemical compound COC1=NC=NC2=C1N=C(N=C(SC)SC)S2 HUBRSUQLBOOYKF-UHFFFAOYSA-N 0.000 description 1
- FBMCKFANBCCIFK-UHFFFAOYSA-N n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]imidazole-1-carbothioamide Chemical compound C1=CC(OC)=CC=C1C1=CSC(NC(=S)N2C=NC=C2)=N1 FBMCKFANBCCIFK-UHFFFAOYSA-N 0.000 description 1
- NPLRRFUPFJMICF-UHFFFAOYSA-N n-[4-(4-methoxyphenyl)-5-methyl-1,3-thiazol-2-yl]imidazole-1-carbothioamide Chemical compound C1=CC(OC)=CC=C1C1=C(C)SC(NC(=S)N2C=NC=C2)=N1 NPLRRFUPFJMICF-UHFFFAOYSA-N 0.000 description 1
- OZEMQJOXYRKPEG-UHFFFAOYSA-N n-[4-(4-methoxyphenyl)-5-methyl-1,3-thiazol-2-yl]spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole]-2'-amine Chemical compound C1=CC(OC)=CC=C1C1=C(C)SC(NC=2OC3(C4CCN(CC4)C3)CN=2)=N1 OZEMQJOXYRKPEG-UHFFFAOYSA-N 0.000 description 1
- YBDKBVGKMUKXGV-UHFFFAOYSA-N n-[6-(difluoromethoxy)-1,3-benzothiazol-2-yl]imidazole-1-carbothioamide Chemical compound S1C2=CC(OC(F)F)=CC=C2N=C1NC(=S)N1C=CN=C1 YBDKBVGKMUKXGV-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007996 neuronal plasticity Effects 0.000 description 1
- 239000000181 nicotinic agonist Substances 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- JLZXCVHSDMLGJO-UHFFFAOYSA-N pyrimidin-2-yl carbamodithioate Chemical compound NC(=S)Sc1ncccn1 JLZXCVHSDMLGJO-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical compound C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 1
- 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- MRTAVLDNYYEJHK-UHFFFAOYSA-M sodium;2-chloro-2,2-difluoroacetate Chemical compound [Na+].[O-]C(=O)C(F)(F)Cl MRTAVLDNYYEJHK-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- IQZSFDJPGKPJOF-UHFFFAOYSA-N spiro[1-azabicyclo[2.2.2]octane-3,5'-4h-1,3-oxazole] Chemical compound C1N=COC11C(CC2)CCN2C1 IQZSFDJPGKPJOF-UHFFFAOYSA-N 0.000 description 1
- NRUGQHBSEHPWRL-UHFFFAOYSA-N spiro[2H-1,3-oxazole-5,2'-bicyclo[2.2.2]octane] Chemical compound C12CC3(C(CC1)CC2)C=NCO3 NRUGQHBSEHPWRL-UHFFFAOYSA-N 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000015883 synaptic transmission, dopaminergic Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 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
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- LYTCVQQGCSNFJU-LKGYBJPKSA-N α-bungarotoxin Chemical compound C(/[C@H]1O[C@H]2C[C@H]3O[C@@H](CC(=C)C=O)C[C@H](O)[C@]3(C)O[C@@H]2C[C@@H]1O[C@@H]1C2)=C/C[C@]1(C)O[C@H]1[C@@]2(C)O[C@]2(C)CC[C@@H]3O[C@@H]4C[C@]5(C)O[C@@H]6C(C)=CC(=O)O[C@H]6C[C@H]5O[C@H]4C[C@@H](C)[C@H]3O[C@H]2C1 LYTCVQQGCSNFJU-LKGYBJPKSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/20—Spiro-condensed 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4721108P | 2008-04-23 | 2008-04-23 | |
| US12/423,299 US7863291B2 (en) | 2008-04-23 | 2009-04-14 | Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2271650E true PT2271650E (pt) | 2015-12-01 |
Family
ID=41215599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT97339493T PT2271650E (pt) | 2008-04-23 | 2009-04-20 | Compostos de quinuclidina como ligandos de recetor de acetilcolina alfa-7-nicotínica |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7863291B2 (OSRAM) |
| EP (1) | EP2271650B1 (OSRAM) |
| JP (1) | JP5389905B2 (OSRAM) |
| KR (1) | KR20110015565A (OSRAM) |
| CN (1) | CN102066384B (OSRAM) |
| AR (1) | AR071215A1 (OSRAM) |
| AU (1) | AU2009239575B2 (OSRAM) |
| BR (1) | BRPI0911542A2 (OSRAM) |
| CA (1) | CA2722325A1 (OSRAM) |
| CL (1) | CL2009000975A1 (OSRAM) |
| CO (1) | CO6300941A2 (OSRAM) |
| CY (1) | CY1117045T1 (OSRAM) |
| DK (1) | DK2271650T3 (OSRAM) |
| EA (1) | EA017628B1 (OSRAM) |
| ES (1) | ES2553753T3 (OSRAM) |
| HR (1) | HRP20151111T1 (OSRAM) |
| HU (1) | HUE028302T2 (OSRAM) |
| IL (1) | IL208673A (OSRAM) |
| MX (1) | MX2010011374A (OSRAM) |
| NZ (1) | NZ588649A (OSRAM) |
| PE (1) | PE20091977A1 (OSRAM) |
| PL (1) | PL2271650T3 (OSRAM) |
| PT (1) | PT2271650E (OSRAM) |
| SI (1) | SI2271650T1 (OSRAM) |
| TW (1) | TWI431007B (OSRAM) |
| WO (1) | WO2009131926A1 (OSRAM) |
| ZA (1) | ZA201007527B (OSRAM) |
Families Citing this family (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8309577B2 (en) * | 2008-04-23 | 2012-11-13 | Bristol-Myers Squibb Company | Quinuclidine compounds as α-7 nicotinic acetylcholine receptor ligands |
| HUE038946T2 (hu) | 2008-04-23 | 2018-12-28 | Gilead Sciences Inc | 1'-szubsztituált carba-nukleozid analógok antivirális kezelésre |
| KR20110092266A (ko) * | 2008-08-04 | 2011-08-17 | 씨에이치디아이 파운데이션, 인코포레이티드 | 소정 키누레닌-3-모노옥시게나아제 억제제, 약학적 조성물, 및 그의 사용 방법 |
| TWI453207B (zh) * | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶，其組合物及使用其之治療方法 |
| JP5767643B2 (ja) | 2009-09-21 | 2015-08-19 | ギリード・サイエンシズ・インコーポレーテッド | １’−置換カルバヌクレオシド類似体の調製のためのプロセスおよび中間体 |
| US8278320B2 (en) | 2009-10-28 | 2012-10-02 | Bristol-Myers Squibb Company | Azabicyclo[2.2.1]heptane compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| JP2013509417A (ja) * | 2009-10-28 | 2013-03-14 | ブリストル−マイヤーズ スクイブ カンパニー | α７ニコチン性アセチルコリン受容体リガンドとしてのアザ二環式化合物 |
| CN102791718B (zh) * | 2009-10-29 | 2015-11-25 | 百时美施贵宝公司 | 作为α-7烟碱乙酰胆碱受体配体的奎宁环化合物 |
| BR112012017484A2 (pt) * | 2010-01-14 | 2020-08-25 | Sanofi | "derivados de oxazolopirimidina 2,5-substituídos" |
| JP2013525457A (ja) | 2010-04-30 | 2013-06-20 | ブリストル−マイヤーズ スクイブ カンパニー | アルファ−７ニコチン性アセチルコリン受容体リガンドプロドラッグとしてのアザ−二環式アミンｎ−オキシド化合物 |
| PL2589592T3 (pl) | 2010-06-30 | 2019-03-29 | Fujifilm Corporation | Nowe pochodne nikotynamidu lub ich sole |
| KR101995598B1 (ko) | 2010-07-19 | 2019-07-02 | 길리애드 사이언시즈, 인코포레이티드 | 부분입체 이성질성으로 순수한 포스포라미데이트 전구약물의 제조 방법 |
| PE20130400A1 (es) | 2010-07-22 | 2013-04-10 | Gilead Sciences Inc | Metodos y compuestos para tratar infecciones virales por paramyxoviridae |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| TWI565709B (zh) | 2011-07-19 | 2017-01-11 | 英菲尼提製藥股份有限公司 | 雜環化合物及其用途 |
| MY166890A (en) | 2011-08-30 | 2018-07-24 | Chdi Foundation Inc | Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
| SI2766359T1 (sl) | 2011-10-14 | 2016-09-30 | Ambit Biosciences Corporation | Heterociklične spojine in njihova uporaba kot modulatorjev receptorja tirozin kinaze tipa III |
| AR090037A1 (es) | 2011-11-15 | 2014-10-15 | Xention Ltd | Derivados de tieno y/o furo-pirimidinas y piridinas inhibidores de los canales de potasio |
| EP2855471B1 (en) | 2012-05-24 | 2017-11-15 | Bristol-Myers Squibb Company | QUINUCLIDINE, 1-AZABICYCLO[2.2.1]HEPTANE, 1-AZABICYCLO [3.2.1]OCTANE, and 1-AZABICYCLO[3.2.2]NONANE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS |
| SI2861595T1 (sl) | 2012-06-13 | 2017-04-26 | Incyte Holdings Corporation | Substituirane triciklične spojine kot inhibitorji fgfr |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| HUE043398T2 (hu) | 2013-03-14 | 2019-08-28 | Merck Patent Gmbh | Glikozidáz inhibítorok |
| LT2986610T (lt) | 2013-04-19 | 2018-04-10 | Incyte Holdings Corporation | Bicikliniai heterociklai, kaip fgfr inhibitoriai |
| KR102408261B1 (ko) | 2014-02-03 | 2022-06-10 | 비타이 파마슈티컬즈, 엘엘씨 | Ror-감마의 디하이드로피롤로피리딘 저해제 |
| JP5714745B2 (ja) * | 2014-04-28 | 2015-05-07 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | α７ニコチン性アセチルコリン受容体リガンドとしてのキヌクリジン化合物 |
| JP2017520610A (ja) | 2014-07-17 | 2017-07-27 | シーエイチディーアイ ファウンデーション，インコーポレーテッド | Ｈｉｖ関連障害を治療するための方法及び組成物 |
| KR102043337B1 (ko) | 2014-08-28 | 2019-11-11 | 아셰뉴론 에스아 | 글리코시다제 저해제 |
| UA118989C2 (uk) | 2014-10-14 | 2019-04-10 | Вітае Фармасьютікалс, Інк. | Дигідропіролопіридинові інгібітори ror-гамма |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| TWI698444B (zh) | 2014-10-29 | 2020-07-11 | 美商基利科學股份有限公司 | 製備核糖苷的方法 |
| EP3215512A1 (en) | 2014-11-04 | 2017-09-13 | Bristol-Myers Squibb Company | Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| US9845308B2 (en) | 2014-11-05 | 2017-12-19 | Vitae Pharmaceuticals, Inc. | Isoindoline inhibitors of ROR-gamma |
| US9663515B2 (en) | 2014-11-05 | 2017-05-30 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| SG10201913036RA (en) | 2015-02-20 | 2020-02-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| EP3331876B1 (en) | 2015-08-05 | 2020-10-07 | Vitae Pharmaceuticals, LLC | Modulators of ror-gamma |
| PT3349758T (pt) | 2015-09-16 | 2022-07-13 | Gilead Sciences Inc | Métodos para o tratamento de infeções pelo vírus arenaviridae |
| KR20180086221A (ko) | 2015-11-20 | 2018-07-30 | 비타이 파마슈티컬즈, 인코포레이티드 | Ror-감마의 조절물질 |
| TWI757266B (zh) | 2016-01-29 | 2022-03-11 | 美商維它藥物有限責任公司 | ＲＯＲ－γ調節劑 |
| KR102800480B1 (ko) | 2016-02-25 | 2025-04-25 | 아셰뉴론 에스아 | 피페라진 유도체의 산 부가 염 |
| US11261183B2 (en) | 2016-02-25 | 2022-03-01 | Asceneuron Sa | Sulfoximine glycosidase inhibitors |
| MA43680A (fr) | 2016-02-25 | 2018-11-28 | Asceneuron Sa | Inhibiteurs de glycosidases |
| MA43677A (fr) | 2016-02-25 | 2018-11-28 | Asceneuron Sa | Inhibiteurs de glycosidases |
| US9481674B1 (en) | 2016-06-10 | 2016-11-01 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| CN110869028B (zh) | 2017-03-14 | 2023-01-20 | 吉利德科学公司 | 治疗猫冠状病毒感染的方法 |
| MA48994A (fr) | 2017-03-30 | 2020-02-05 | Hoffmann La Roche | Isoquinoléines utilisées en tant qu'inhibiteurs de hpk1 |
| KR102510784B1 (ko) | 2017-03-30 | 2023-03-15 | 엑스더블유파마 리미티드 | 이환형 헤테로아릴 유도체 및 이의 제조 및 용도 |
| KR20190141747A (ko) | 2017-05-01 | 2019-12-24 | 길리애드 사이언시즈, 인코포레이티드 | (S)-2-에틸부틸 2-(((S)-(((2R,3S,4R,5R)-5-(4-아미노피롤로[2,1-f] [1,2,4]트리아진-7-일)-5-시아노-3,4-디히드록시테트라히드로푸란-2-일)메톡시)(페녹시) 포스포릴)아미노)프로파노에이트의 결정질 형태 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| US10675296B2 (en) | 2017-07-11 | 2020-06-09 | Gilead Sciences, Inc. | Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections |
| WO2019018975A1 (en) | 2017-07-24 | 2019-01-31 | Vitae Pharmaceuticals, Inc. | INHIBITORS OF ROR GAMMA |
| IL298639A (en) | 2017-07-24 | 2023-01-01 | Vitae Pharmaceuticals Llc | Inhibitors of gamma ror |
| EP3672959A1 (en) | 2017-08-24 | 2020-07-01 | Asceneuron SA | Linear glycosidase inhibitors |
| CN107868039A (zh) * | 2017-11-27 | 2018-04-03 | 中国药科大学 | 一种贝曲沙班中间体n－（5－氯－2－吡啶基）－2－［（4－氰基苯甲酰基）氨基］－5－甲氧基苯甲酰胺的制备方法 |
| PL3788047T3 (pl) | 2018-05-04 | 2025-04-14 | Incyte Corporation | Stałe postacie inhibitora fgfr i sposoby ich otrzymywania |
| KR20210018264A (ko) | 2018-05-04 | 2021-02-17 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| EP3826722A1 (en) | 2018-07-24 | 2021-06-02 | F. Hoffmann-La Roche AG | Isoquinoline compounds and uses thereof |
| US12016852B2 (en) | 2018-08-22 | 2024-06-25 | Asceneuron Sa | Pyrrolidine glycosidase inhibitors |
| SG11202101651RA (en) | 2018-08-22 | 2021-03-30 | Asceneuron S A | Succinate and fumarate acid addition salts of piperazine derivatives useful as glycosidase inhibitors |
| US11795165B2 (en) | 2018-08-22 | 2023-10-24 | Asceneuron Sa | Tetrahydro-benzoazepine glycosidase inhibitors |
| WO2020039029A1 (en) | 2018-08-22 | 2020-02-27 | Asceneuron S. A. | Spiro compounds as glycosidase inhibitors |
| TW202024053A (zh) | 2018-10-02 | 2020-07-01 | 美商建南德克公司 | 異喹啉化合物及其用途 |
| US11612606B2 (en) | 2018-10-03 | 2023-03-28 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021039968A1 (ja) | 2019-08-30 | 2021-03-04 | 大日本住友製薬株式会社 | ２－アミノキナゾリノン誘導体 |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CR20220169A (es) | 2019-10-14 | 2022-10-27 | Incyte Corp | Heterociclos bicíclicos como inhibidores de fgfr |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤としての三環式複素環 |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| CN118766947A (zh) | 2020-01-27 | 2024-10-15 | 吉利德科学公司 | 用于治疗SARS CoV-2感染的方法 |
| CA3169340A1 (en) | 2020-03-12 | 2021-09-16 | Pavel R. Badalov | Methods of preparing 1'-cyano nucleosides |
| JP7482250B2 (ja) | 2020-04-06 | 2024-05-13 | ギリアード サイエンシーズ， インコーポレイテッド | １’－シアノ置換カルバヌクレオシド類似体の吸入製剤 |
| PL4157272T3 (pl) | 2020-05-29 | 2025-10-20 | Gilead Sciences, Inc. | Remdesiwir do leczenia zakażeń wirusowych |
| JP2023531524A (ja) | 2020-06-24 | 2023-07-24 | ギリアード サイエンシーズ， インコーポレイテッド | １’－シアノヌクレオシド類似体及びその使用 |
| LT4204421T (lt) | 2020-08-27 | 2024-06-25 | Gilead Sciences, Inc. | Virusinių infekcijų gydymui skirti junginiai ir būdai |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含ｆｇｆｒ抑制劑及ｎｅｃｔｉｎ－４靶向劑之組合療法 |
| EP4352060A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US11939331B2 (en) | 2021-06-09 | 2024-03-26 | Incyte Corporation | Tricyclic heterocycles as FGFR inhibitors |
| US20230295172A1 (en) | 2022-03-02 | 2023-09-21 | Gilead Sciences, Inc. | Compounds and methods for treatment of viral infections |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8808433D0 (en) | 1988-04-11 | 1988-05-11 | Merck Sharp & Dohme | Therapeutic agents |
| US5053412A (en) * | 1990-04-10 | 1991-10-01 | Israel Institute For Biological Research | Spiro nitrogen-bridged heterocyclic compounds |
| US5534520A (en) * | 1990-04-10 | 1996-07-09 | Fisher; Abraham | Spiro compounds containing five-membered rings |
| IL97726A (en) * | 1990-04-10 | 1994-12-29 | Israel Inst Biolog Res | Pharmaceutical compositions containing compounds with bridged and unbridged heterocyclic groups, spiro-connected with oxazoline and thiazoline groups, and some new such compounds |
| UA54375C2 (uk) | 1994-08-24 | 2003-03-17 | Астра Актієболаг | Спіро-азабіциклічні сполуки, способи їх одержання та фармацевтична композиція |
| EP1507765A4 (en) | 2002-05-03 | 2006-11-02 | Israel Inst Biolog Res | METHODS AND COMPOSITIONS FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM AND PERIPHERAL NERVOUS SYSTEM DISORDERS AND RELATED COMPOUNDS |
| KR20060057569A (ko) | 2003-07-08 | 2006-05-26 | 아스트라제네카 아베 | 알파7 니코틴계 아세틸콜린 수용체와 친화도를 갖는스피로[1-아자비시클로[2.2.2]옥탄-3,5'-옥사졸리딘-2'-온] 유도체 |
| BRPI0518949A2 (pt) | 2004-12-15 | 2008-12-16 | Astrazeneca Ab | composto, uso de um composto, mÉtodo para induÇço da interrupÇço do hÁbito de fumar, composiÇço farmacÊutica, e, uso de uma composiÇço farmacÊutica |
| US20070004715A1 (en) * | 2005-06-30 | 2007-01-04 | Yifang Huang | Novel spiro-quinuclidinyl derivatives for the treatment of central nervous system disorders |
| ITMI20061279A1 (it) | 2006-06-30 | 2008-01-01 | Consiglio Nazionale Ricerche | Agonisti nicotinici selettivi per il sottotipo recettoriale alfa7,procedimento per la loro preparazione e relative composizioni farmaceutiche |
| US8309577B2 (en) * | 2008-04-23 | 2012-11-13 | Bristol-Myers Squibb Company | Quinuclidine compounds as α-7 nicotinic acetylcholine receptor ligands |
-
2009
- 2009-04-14 US US12/423,299 patent/US7863291B2/en active Active
- 2009-04-20 HU HUE09733949A patent/HUE028302T2/en unknown
- 2009-04-20 SI SI200931324T patent/SI2271650T1/sl unknown
- 2009-04-20 ES ES09733949.3T patent/ES2553753T3/es active Active
- 2009-04-20 DK DK09733949.3T patent/DK2271650T3/en active
- 2009-04-20 PL PL09733949T patent/PL2271650T3/pl unknown
- 2009-04-20 KR KR1020107026057A patent/KR20110015565A/ko not_active Ceased
- 2009-04-20 CA CA2722325A patent/CA2722325A1/en not_active Abandoned
- 2009-04-20 JP JP2011506374A patent/JP5389905B2/ja not_active Expired - Fee Related
- 2009-04-20 EP EP09733949.3A patent/EP2271650B1/en active Active
- 2009-04-20 CN CN200980123841.9A patent/CN102066384B/zh not_active Expired - Fee Related
- 2009-04-20 PT PT97339493T patent/PT2271650E/pt unknown
- 2009-04-20 HR HRP20151111TT patent/HRP20151111T1/hr unknown
- 2009-04-20 BR BRPI0911542A patent/BRPI0911542A2/pt not_active IP Right Cessation
- 2009-04-20 MX MX2010011374A patent/MX2010011374A/es active IP Right Grant
- 2009-04-20 WO PCT/US2009/041076 patent/WO2009131926A1/en not_active Ceased
- 2009-04-20 NZ NZ588649A patent/NZ588649A/en unknown
- 2009-04-20 EA EA201001696A patent/EA017628B1/ru not_active IP Right Cessation
- 2009-04-20 AU AU2009239575A patent/AU2009239575B2/en not_active Ceased
- 2009-04-23 TW TW098113525A patent/TWI431007B/zh not_active IP Right Cessation
- 2009-04-23 PE PE2009000562A patent/PE20091977A1/es not_active Application Discontinuation
- 2009-04-23 CL CL2009000975A patent/CL2009000975A1/es unknown
- 2009-04-23 AR ARP090101442A patent/AR071215A1/es unknown
-
2010
- 2010-10-12 IL IL208673A patent/IL208673A/en not_active IP Right Cessation
- 2010-10-21 ZA ZA2010/07527A patent/ZA201007527B/en unknown
- 2010-10-22 CO CO10131169A patent/CO6300941A2/es active IP Right Grant
-
2015
- 2015-12-14 CY CY20151101139T patent/CY1117045T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2271650T3 (en) | QUINUCLIDE COMPOUNDS LIKE ALPHA-7 NICOTINACETYLCHOLINE RECEPTOR LIGANDS | |
| US8309577B2 (en) | Quinuclidine compounds as α-7 nicotinic acetylcholine receptor ligands | |
| EP2855471B1 (en) | QUINUCLIDINE, 1-AZABICYCLO[2.2.1]HEPTANE, 1-AZABICYCLO [3.2.1]OCTANE, and 1-AZABICYCLO[3.2.2]NONANE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS | |
| JP5619907B2 (ja) | α７ニコチン性アセチルコリン受容体リガンドとしてのキヌクリジン化合物 | |
| EP2493893B1 (en) | Azabicyclo[2.2.1]heptane compounds as alpha-7 nicotinic acetylcholine receptor ligands | |
| EP2493894B1 (en) | Azabicyclic compounds as alpha-7 nicotinic acetylcholine receptor ligands | |
| JP5714745B2 (ja) | α７ニコチン性アセチルコリン受容体リガンドとしてのキヌクリジン化合物 |