SK10542003A3 - N-Substituované nearylové heterocyklické zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents
N-Substituované nearylové heterocyklické zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK10542003A3 SK10542003A3 SK1054-2003A SK10542003A SK10542003A3 SK 10542003 A3 SK10542003 A3 SK 10542003A3 SK 10542003 A SK10542003 A SK 10542003A SK 10542003 A3 SK10542003 A3 SK 10542003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- aryl
- pharmaceutically acceptable
- trifluoromethyl
- chloro
- Prior art date
Links
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 title abstract description 14
- 239000005557 antagonist Substances 0.000 title abstract description 14
- 108010038912 Retinoid X Receptors Proteins 0.000 title abstract description 11
- 102000034527 Retinoid X Receptors Human genes 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 221
- 150000003839 salts Chemical class 0.000 claims abstract description 110
- 208000002193 Pain Diseases 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 556
- -1 aryl heterocyclic compounds Chemical class 0.000 claims description 440
- 125000001424 substituent group Chemical group 0.000 claims description 181
- 125000003118 aryl group Chemical group 0.000 claims description 155
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 130
- 125000003545 alkoxy group Chemical group 0.000 claims description 123
- 125000001153 fluoro group Chemical group F* 0.000 claims description 97
- 239000000460 chlorine Substances 0.000 claims description 85
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 80
- 229910052731 fluorine Inorganic materials 0.000 claims description 77
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 74
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 72
- 229910052799 carbon Inorganic materials 0.000 claims description 62
- 125000001072 heteroaryl group Chemical group 0.000 claims description 60
- 125000000304 alkynyl group Chemical group 0.000 claims description 48
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 34
- 229910052801 chlorine Inorganic materials 0.000 claims description 34
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 33
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 33
- 229910052794 bromium Inorganic materials 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 32
- 239000011737 fluorine Substances 0.000 claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 125000001246 bromo group Chemical group Br* 0.000 claims description 25
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 20
- 125000000335 thiazolyl group Chemical group 0.000 claims description 20
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 16
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 16
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 16
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 15
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 15
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 15
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 14
- QUIJMHDIAFOPRK-UHFFFAOYSA-N 1-cyclooctylazocane Chemical group C1CCCCCCC1N1CCCCCCC1 QUIJMHDIAFOPRK-UHFFFAOYSA-N 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 241001645982 Crax Species 0.000 claims 1
- 239000013256 coordination polymer Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 297
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 192
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 161
- 239000000243 solution Substances 0.000 description 153
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- 239000000203 mixture Substances 0.000 description 143
- 235000019439 ethyl acetate Nutrition 0.000 description 109
- 238000005481 NMR spectroscopy Methods 0.000 description 107
- 239000011541 reaction mixture Substances 0.000 description 100
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 84
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 83
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
- 239000003921 oil Substances 0.000 description 68
- 235000019198 oils Nutrition 0.000 description 67
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 65
- 230000002829 reductive effect Effects 0.000 description 63
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 54
- 239000012267 brine Substances 0.000 description 54
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
- 239000007787 solid Substances 0.000 description 54
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 53
- 239000012044 organic layer Substances 0.000 description 47
- 229910052739 hydrogen Inorganic materials 0.000 description 45
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- 239000011734 sodium Substances 0.000 description 44
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 239000002904 solvent Substances 0.000 description 38
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 35
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- ABJVEAFRFGTATH-UHFFFAOYSA-N benzyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound C1CC(CN)CCN1C(=O)OCC1=CC=CC=C1 ABJVEAFRFGTATH-UHFFFAOYSA-N 0.000 description 31
- 239000012043 crude product Substances 0.000 description 31
- 238000010898 silica gel chromatography Methods 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 239000000543 intermediate Substances 0.000 description 30
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 28
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 28
- 238000000034 method Methods 0.000 description 28
- 238000010992 reflux Methods 0.000 description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 27
- 239000001257 hydrogen Substances 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 25
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 24
- 101150065749 Churc1 gene Proteins 0.000 description 24
- 102100038239 Protein Churchill Human genes 0.000 description 24
- 229920006395 saturated elastomer Polymers 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 238000004587 chromatography analysis Methods 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 238000000746 purification Methods 0.000 description 20
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 19
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 13
- KLPGAGFVEHPRGC-UHFFFAOYSA-N [1-(2-phenylethylsulfonyl)piperidin-4-yl]methanamine Chemical compound C1CC(CN)CCN1S(=O)(=O)CCC1=CC=CC=C1 KLPGAGFVEHPRGC-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 239000007868 Raney catalyst Substances 0.000 description 11
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 11
- 229910000564 Raney nickel Inorganic materials 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 229960004979 fampridine Drugs 0.000 description 11
- MLCNOCRGSBCAGH-UHFFFAOYSA-N 2,3-dichloropyrazine Chemical compound ClC1=NC=CN=C1Cl MLCNOCRGSBCAGH-UHFFFAOYSA-N 0.000 description 10
- AGYUQBNABXVWMS-UHFFFAOYSA-N 2-chloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1 AGYUQBNABXVWMS-UHFFFAOYSA-N 0.000 description 10
- 206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 10
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- YSIALVLPAPHPRR-UHFFFAOYSA-N [2-[[8-amino-4,6-dimethyl-7-oxo-1,9-bis[[7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]carbamoyl]phenoxazin-3-yl]amino]-2-oxoethyl] 2-amino-3-methylbutanoate Chemical compound CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2C1=NC1=C(C(=O)NC3C(NC(C(=O)N4CCCC4C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC3C)C(C)C)=O)C=C(NC(=O)COC(=O)C(N)C(C)C)C(C)=C1O2 YSIALVLPAPHPRR-UHFFFAOYSA-N 0.000 description 9
- 108700015901 actinomycin D1 Proteins 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000003039 volatile agent Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- APRMCBSTMFKLEI-UHFFFAOYSA-N 2-chloro-5-methylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1 APRMCBSTMFKLEI-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
- SEGUUECEFSYLBO-UHFFFAOYSA-N [2-[[1-[2-[[8-amino-4,6-dimethyl-7-oxo-1,9-bis[[7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]carbamoyl]phenoxazin-3-yl]amino]-2-oxoethoxy]-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl] 2-am Chemical compound CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2C1=NC1=C(C(=O)NC3C(NC(C(=O)N4CCCC4C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC3C)C(C)C)=O)C=C(NC(=O)COC(=O)C(C(C)C)NC(=O)COC(=O)C(N)C(C)C)C(C)=C1O2 SEGUUECEFSYLBO-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- OOIJMSVOEKAGEL-UHFFFAOYSA-N benzyl 4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C=CN=CC=2)CCN1C(=O)OCC1=CC=CC=C1 OOIJMSVOEKAGEL-UHFFFAOYSA-N 0.000 description 7
- URRZRARPPRJEEK-UHFFFAOYSA-N benzyl 4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 URRZRARPPRJEEK-UHFFFAOYSA-N 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- FCYRJNVPGSSPBN-UHFFFAOYSA-N (4-methylphenyl)methyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CN)CC1 FCYRJNVPGSSPBN-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 108700015902 actinomycin D2 Proteins 0.000 description 6
- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 6
- RBKBGIONDAWNLO-UHFFFAOYSA-N benzyl 4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2N=CC=CN=2)CCN1C(=O)OCC1=CC=CC=C1 RBKBGIONDAWNLO-UHFFFAOYSA-N 0.000 description 6
- MKWNLCUQCNEEFC-UHFFFAOYSA-N benzyl 4-[[(6-chloropyridazin-3-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=NC(Cl)=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 MKWNLCUQCNEEFC-UHFFFAOYSA-N 0.000 description 6
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 6
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 6
- 108091008757 nuclear thyroid hormone receptors Proteins 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000004237 preparative chromatography Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 229960002317 succinimide Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 5
- WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 5
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 5
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- LVZARJOZJFAOQF-UHFFFAOYSA-N benzyl 3-(aminomethyl)pyrrolidine-1-carboxylate Chemical compound C1C(CN)CCN1C(=O)OCC1=CC=CC=C1 LVZARJOZJFAOQF-UHFFFAOYSA-N 0.000 description 5
- MBZIWEUFYQNFSU-UHFFFAOYSA-N benzyl 4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 MBZIWEUFYQNFSU-UHFFFAOYSA-N 0.000 description 5
- PYARCEFRYZTEDM-UHFFFAOYSA-N benzyl 4-[[(3-fluoropyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1=CC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 PYARCEFRYZTEDM-UHFFFAOYSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 5
- DQXNTSXKIUZJJS-UHFFFAOYSA-N 2,4-dichloro-5-methylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1Cl DQXNTSXKIUZJJS-UHFFFAOYSA-N 0.000 description 4
- SVAZIMBLBHOVIR-UHFFFAOYSA-N 2-chloro-3-fluoropyridine Chemical compound FC1=CC=CN=C1Cl SVAZIMBLBHOVIR-UHFFFAOYSA-N 0.000 description 4
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 4
- FFPGRZSYIGTPEB-UHFFFAOYSA-N 3-methoxy-5-methyl-n-(piperidin-4-ylmethyl)pyrazin-2-amine Chemical compound COC1=NC(C)=CN=C1NCC1CCNCC1 FFPGRZSYIGTPEB-UHFFFAOYSA-N 0.000 description 4
- VYTXLSQVYGNWLV-UHFFFAOYSA-N 4-(2-thienyl)butyric acid Chemical compound OC(=O)CCCC1=CC=CS1 VYTXLSQVYGNWLV-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
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 4
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- 102000038100 NR2 subfamily Human genes 0.000 description 4
- 108020002076 NR2 subfamily Proteins 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical group OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- ZWSODYYGCWFNGY-XZOQPEGZSA-N [(1r,2r)-2-phenylcyclopropyl]-[4-[[[5-(2-trimethylsilylethynyl)pyrimidin-2-yl]amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(C#C[Si](C)(C)C)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 ZWSODYYGCWFNGY-XZOQPEGZSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- LOGBGAOKQMDEGD-SJLPKXTDSA-N benzyl (3s,4r)-3-hydroxy-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C([C@H]1CCN(C[C@H]1O)C(=O)OCC=1C=CC=CC=1)NC1=CC=NC=C1 LOGBGAOKQMDEGD-SJLPKXTDSA-N 0.000 description 4
- RFKYTAKHQSLVEC-CHWSQXEVSA-N benzyl (3s,4r)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate Chemical compound C1[C@@H](O)[C@@H](CN)CCN1C(=O)OCC1=CC=CC=C1 RFKYTAKHQSLVEC-CHWSQXEVSA-N 0.000 description 4
- ZFDAYTKMBXFWFV-UHFFFAOYSA-N benzyl 4-[(3-methylpyridin-2-yl)carbamoyl]piperidine-1-carboxylate Chemical compound CC1=CC=CN=C1NC(=O)C1CCN(C(=O)OCC=2C=CC=CC=2)CC1 ZFDAYTKMBXFWFV-UHFFFAOYSA-N 0.000 description 4
- BLTHIBQLIDISKV-UHFFFAOYSA-N benzyl 4-[[(2-chloro-5-fluoropyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1=CN=C(Cl)N=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 BLTHIBQLIDISKV-UHFFFAOYSA-N 0.000 description 4
- UTWASDYYIJLITL-UHFFFAOYSA-N benzyl 4-[[(2-chloro-6-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=NC(C)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 UTWASDYYIJLITL-UHFFFAOYSA-N 0.000 description 4
- QHVWTOSRDBMVSO-UHFFFAOYSA-N benzyl 4-[[(5,6-dichloropyridazin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=NN=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1Cl QHVWTOSRDBMVSO-UHFFFAOYSA-N 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000007979 citrate buffer Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- HGVWYJYXIXTXDH-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)pyridazin-4-amine Chemical compound C1CNCCC1CNC1=CC=NN=C1 HGVWYJYXIXTXDH-UHFFFAOYSA-N 0.000 description 4
- PLJYCBORBFVHSM-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)pyridin-4-amine Chemical compound C1CNCCC1CNC1=CC=NC=C1 PLJYCBORBFVHSM-UHFFFAOYSA-N 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 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
- 238000001665 trituration Methods 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- OUUVDKAYACQKRO-UHFFFAOYSA-N (4-cyclopropylphenyl)methanol Chemical compound C1=CC(CO)=CC=C1C1CC1 OUUVDKAYACQKRO-UHFFFAOYSA-N 0.000 description 3
- VAWDNPHZWRMZSS-UHFFFAOYSA-N (4-cyclopropylphenyl)methyl 4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)OCC=2C=CC(=CC=2)C2CC2)CC1 VAWDNPHZWRMZSS-UHFFFAOYSA-N 0.000 description 3
- ZTFHMKNXDDIIHO-UHFFFAOYSA-N (4-fluorophenyl)methyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound C1CC(CN)CCN1C(=O)OCC1=CC=C(F)C=C1 ZTFHMKNXDDIIHO-UHFFFAOYSA-N 0.000 description 3
- UAGWKSBWWWEOLT-IEBWSBKVSA-N (4-methylphenyl)methyl (3s,4r)-3-hydroxy-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1C[C@@H](O)[C@@H](CNC=2C=CN=CC=2)CC1 UAGWKSBWWWEOLT-IEBWSBKVSA-N 0.000 description 3
- WCRDXUBMSYRLDN-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[(3-methylpyridin-2-yl)carbamoyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(C(=O)NC=2C(=CC=CN=2)C)CC1 WCRDXUBMSYRLDN-UHFFFAOYSA-N 0.000 description 3
- FRFKHEOXGIRWBR-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(2-methylsulfanylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CSC1=NC=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC(C)=CC=2)=N1 FRFKHEOXGIRWBR-UHFFFAOYSA-N 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- PAZOUOCFOKZLSA-UHFFFAOYSA-N 1-benzyl-4-(hydroxymethyl)piperidin-3-ol Chemical compound C1C(O)C(CO)CCN1CC1=CC=CC=C1 PAZOUOCFOKZLSA-UHFFFAOYSA-N 0.000 description 3
- HASDISHWDYOVKZ-UHFFFAOYSA-N 1-o-benzyl 4-o-tert-butyl 2-(aminomethyl)-4-hydroxypiperidine-1,4-dicarboxylate Chemical compound NCC1CC(C(=O)OC(C)(C)C)(O)CCN1C(=O)OCC1=CC=CC=C1 HASDISHWDYOVKZ-UHFFFAOYSA-N 0.000 description 3
- NZJKEQFPRPAEPO-UHFFFAOYSA-N 1h-benzimidazol-4-amine Chemical compound NC1=CC=CC2=C1N=CN2 NZJKEQFPRPAEPO-UHFFFAOYSA-N 0.000 description 3
- OLDXGEXZLWOGJN-UHFFFAOYSA-N 2-(2-fluorophenyl)cyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1C1=CC=CC=C1F OLDXGEXZLWOGJN-UHFFFAOYSA-N 0.000 description 3
- FQKROEPGEPPLKM-UHFFFAOYSA-N 2-(5-methylthiophen-2-yl)cyclopropane-1-carboxylic acid Chemical compound S1C(C)=CC=C1C1C(C(O)=O)C1 FQKROEPGEPPLKM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- PGFIHORVILKHIA-UHFFFAOYSA-N 2-bromopyrimidine Chemical compound BrC1=NC=CC=N1 PGFIHORVILKHIA-UHFFFAOYSA-N 0.000 description 3
- DBQFXQNGQUPVER-UHFFFAOYSA-N 2-chloro-4,5-dimethylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1C DBQFXQNGQUPVER-UHFFFAOYSA-N 0.000 description 3
- QDHRSLFSDGCJFX-UHFFFAOYSA-N 3-fluorobenzyl alcohol Chemical compound OCC1=CC=CC(F)=C1 QDHRSLFSDGCJFX-UHFFFAOYSA-N 0.000 description 3
- HHILLXQAOWNWBI-UHFFFAOYSA-N 3-methoxy-n-(piperidin-4-ylmethyl)pyrazin-2-amine Chemical compound COC1=NC=CN=C1NCC1CCNCC1 HHILLXQAOWNWBI-UHFFFAOYSA-N 0.000 description 3
- XWFMJJGVDUMSEU-UHFFFAOYSA-N 4-[(1-phenylmethoxycarbonylpiperidin-4-yl)methylamino]pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 XWFMJJGVDUMSEU-UHFFFAOYSA-N 0.000 description 3
- XKENOTHGZDIXRS-UHFFFAOYSA-N 4-methylsulfanylpteridine Chemical compound C1=CN=C2C(SC)=NC=NC2=N1 XKENOTHGZDIXRS-UHFFFAOYSA-N 0.000 description 3
- XKYRUEVWYNEUKN-UHFFFAOYSA-N 5-methyl-n-(piperidin-4-ylmethyl)pyrimidin-4-amine Chemical compound CC1=CN=CN=C1NCC1CCNCC1 XKYRUEVWYNEUKN-UHFFFAOYSA-N 0.000 description 3
- WGEDIYRXCKDEKB-UHFFFAOYSA-N 6-methoxy-5-(piperidin-4-ylmethylamino)pyrazine-2-carbonitrile Chemical compound COC1=NC(C#N)=CN=C1NCC1CCNCC1 WGEDIYRXCKDEKB-UHFFFAOYSA-N 0.000 description 3
- AUALWNWZEDBUJV-UHFFFAOYSA-N 6-methyl-n-(piperidin-4-ylmethyl)pyrimidin-4-amine Chemical compound C1=NC(C)=CC(NCC2CCNCC2)=N1 AUALWNWZEDBUJV-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
- RAGFOQOSXXFOTI-UHFFFAOYSA-N C1=C[N+]([O-])=CC=C1NC(=O)C1CCN(C(=O)OCC=2C=CC=CC=2)CC1 Chemical compound C1=C[N+]([O-])=CC=C1NC(=O)C1CCN(C(=O)OCC=2C=CC=CC=2)CC1 RAGFOQOSXXFOTI-UHFFFAOYSA-N 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 3
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 102000034570 NR1 subfamily Human genes 0.000 description 3
- 108020001305 NR1 subfamily Proteins 0.000 description 3
- ZHTCPMRUAATOTF-UHFFFAOYSA-N O=C(NCC(CC1)CCN1S(CCC1=CC=CC=C1)(=O)=O)OCC1=CC=CC=C1 Chemical compound O=C(NCC(CC1)CCN1S(CCC1=CC=CC=C1)(=O)=O)OCC1=CC=CC=C1 ZHTCPMRUAATOTF-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- LXCOMZOXSYTNGX-ZWKOTPCHSA-N [4-[[(5-bromopyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound N1=CC(Br)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 LXCOMZOXSYTNGX-ZWKOTPCHSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- WMFIGYVCERGRIG-UHFFFAOYSA-N benzyl 3-[(pyrimidin-2-ylamino)methyl]pyrrolidine-1-carboxylate Chemical compound C1CC(CNC=2N=CC=CN=2)CN1C(=O)OCC1=CC=CC=C1 WMFIGYVCERGRIG-UHFFFAOYSA-N 0.000 description 3
- IJUVVFGCZRZNFB-UHFFFAOYSA-N benzyl 4-(aminomethyl)-4-fluoropiperidine-1-carboxylate Chemical compound C1CC(CN)(F)CCN1C(=O)OCC1=CC=CC=C1 IJUVVFGCZRZNFB-UHFFFAOYSA-N 0.000 description 3
- LWIUVSBTWBNGLT-UHFFFAOYSA-N benzyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate Chemical compound C1CC(CN)(O)CCN1C(=O)OCC1=CC=CC=C1 LWIUVSBTWBNGLT-UHFFFAOYSA-N 0.000 description 3
- QCHGWUWZNNKWFB-UHFFFAOYSA-N benzyl 4-(azidomethyl)-4-fluoropiperidine-1-carboxylate Chemical compound C1CC(F)(CN=[N+]=[N-])CCN1C(=O)OCC1=CC=CC=C1 QCHGWUWZNNKWFB-UHFFFAOYSA-N 0.000 description 3
- JFZLQNFHDTXGEP-UHFFFAOYSA-N benzyl 4-(n-hydroxy-c-methylcarbonimidoyl)piperidine-1-carboxylate Chemical compound C1CC(C(=NO)C)CCN1C(=O)OCC1=CC=CC=C1 JFZLQNFHDTXGEP-UHFFFAOYSA-N 0.000 description 3
- RESRONAXYHGHCE-UHFFFAOYSA-N benzyl 4-(pyridin-4-ylcarbamoyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC=2C=CC=CC=2)CCC1C(=O)NC1=CC=NC=C1 RESRONAXYHGHCE-UHFFFAOYSA-N 0.000 description 3
- ZCFMXURGBZFXOV-UHFFFAOYSA-N benzyl 4-[(pyridazin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C=NN=CC=2)CCN1C(=O)OCC1=CC=CC=C1 ZCFMXURGBZFXOV-UHFFFAOYSA-N 0.000 description 3
- SQOJLAMWWPQVIZ-UHFFFAOYSA-N benzyl 4-[1-(pyridin-4-ylamino)ethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC=2C=CC=CC=2)CCC1C(C)NC1=CC=NC=C1 SQOJLAMWWPQVIZ-UHFFFAOYSA-N 0.000 description 3
- GRCJVKJODLTUSO-UHFFFAOYSA-N benzyl 4-[[(2-chloro-5-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CN=C(Cl)N=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 GRCJVKJODLTUSO-UHFFFAOYSA-N 0.000 description 3
- QALBEHHZLANGHJ-UHFFFAOYSA-N benzyl 4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=CC(C)=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 QALBEHHZLANGHJ-UHFFFAOYSA-N 0.000 description 3
- XLHXIJVMPJZWOU-UHFFFAOYSA-N benzyl 4-[[(6-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=NC(C)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 XLHXIJVMPJZWOU-UHFFFAOYSA-N 0.000 description 3
- RIYFGTCHTDGBNT-UHFFFAOYSA-N benzyl 4-[[[2-(hydroxymethyl)pyridin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1=NC(CO)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 RIYFGTCHTDGBNT-UHFFFAOYSA-N 0.000 description 3
- VOETZCCNDJVWCN-UHFFFAOYSA-N benzyl 4-acetylpiperidine-1-carboxylate Chemical compound C1CC(C(=O)C)CCN1C(=O)OCC1=CC=CC=C1 VOETZCCNDJVWCN-UHFFFAOYSA-N 0.000 description 3
- SQMPZGSUNNMVKE-UHFFFAOYSA-N benzyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound C1CC(CO)(F)CCN1C(=O)OCC1=CC=CC=C1 SQMPZGSUNNMVKE-UHFFFAOYSA-N 0.000 description 3
- SOLRUSNIROEEER-UHFFFAOYSA-N benzyl 4-fluoro-4-(methylsulfonyloxymethyl)piperidine-1-carboxylate Chemical compound C1CC(COS(=O)(=O)C)(F)CCN1C(=O)OCC1=CC=CC=C1 SOLRUSNIROEEER-UHFFFAOYSA-N 0.000 description 3
- ZJQMLJFHCKTCSF-UHFFFAOYSA-N benzyl 4-formylpiperidine-1-carboxylate Chemical compound C1CC(C=O)CCN1C(=O)OCC1=CC=CC=C1 ZJQMLJFHCKTCSF-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- DWMHLKSASWMUFX-UHFFFAOYSA-N ethyl 4-cyclopropylbenzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1CC1 DWMHLKSASWMUFX-UHFFFAOYSA-N 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 229910052748 manganese Inorganic materials 0.000 description 3
- 239000011572 manganese Substances 0.000 description 3
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
- KALKIJXYAIIASF-UHFFFAOYSA-N n-(3-methylpyridin-2-yl)piperidine-4-carboxamide Chemical compound CC1=CC=CN=C1NC(=O)C1CCNCC1 KALKIJXYAIIASF-UHFFFAOYSA-N 0.000 description 3
- FPGDHFZTDDYXOI-UHFFFAOYSA-N n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrimidin-2-amine Chemical compound C1CC(CNC=2N=CC=CN=2)CCN1S(=O)(=O)CCC1=CC=CC=C1 FPGDHFZTDDYXOI-UHFFFAOYSA-N 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 description 3
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- FRPUJESXDNRDLW-UHFFFAOYSA-N tert-butyl 1-(aminomethyl)-4-hydroxypiperidine-4-carboxylate Chemical compound CC(C)(C)OC(=O)C1(O)CCN(CN)CC1 FRPUJESXDNRDLW-UHFFFAOYSA-N 0.000 description 3
- OWGZTEQTKJXHIZ-UHFFFAOYSA-N tert-butyl 2-(5-methylthiophen-2-yl)cyclopropane-1-carboxylate Chemical compound S1C(C)=CC=C1C1C(C(=O)OC(C)(C)C)C1 OWGZTEQTKJXHIZ-UHFFFAOYSA-N 0.000 description 3
- MFPYJRZPFLDVQA-UHFFFAOYSA-N tert-butyl 2-(aminomethyl)-1-benzyl-4-hydroxypiperidine-4-carboxylate Chemical compound NCC1CC(C(=O)OC(C)(C)C)(O)CCN1CC1=CC=CC=C1 MFPYJRZPFLDVQA-UHFFFAOYSA-N 0.000 description 3
- FQUVAASUKJSNRV-UHFFFAOYSA-N tert-butyl 4-(1-aminoethyl)piperidine-1-carboxylate Chemical compound CC(N)C1CCN(C(=O)OC(C)(C)C)CC1 FQUVAASUKJSNRV-UHFFFAOYSA-N 0.000 description 3
- KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 3
- USVGGNAZKFOBBN-UHFFFAOYSA-N tert-butyl 4-(n-hydroxy-c-methylcarbonimidoyl)piperidine-1-carboxylate Chemical compound ON=C(C)C1CCN(C(=O)OC(C)(C)C)CC1 USVGGNAZKFOBBN-UHFFFAOYSA-N 0.000 description 3
- SDYHOTWGKJCOCI-UHFFFAOYSA-N tert-butyl 4-[[(3-methoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC=CN=C1NCC1CCN(C(=O)OC(C)(C)C)CC1 SDYHOTWGKJCOCI-UHFFFAOYSA-N 0.000 description 3
- AJTWQURNQIIDJU-UHFFFAOYSA-N tert-butyl 4-[[(5-bromo-3-methoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC(Br)=CN=C1NCC1CCN(C(=O)OC(C)(C)C)CC1 AJTWQURNQIIDJU-UHFFFAOYSA-N 0.000 description 3
- VHYXAWLOJGIJPC-UHFFFAOYSA-N tert-butyl n-(piperidin-4-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCNCC1 VHYXAWLOJGIJPC-UHFFFAOYSA-N 0.000 description 3
- AHDDRJBFJBDEPW-DTWKUNHWSA-N trans-2-Phenylcyclopropanecarboxylic acid Chemical compound OC(=O)[C@@H]1C[C@H]1C1=CC=CC=C1 AHDDRJBFJBDEPW-DTWKUNHWSA-N 0.000 description 3
- XRRVAYOGHYNCBD-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) (4-methylphenyl)methyl carbonate Chemical compound C1=CC(C)=CC=C1COC(=O)ON1C(=O)CCC1=O XRRVAYOGHYNCBD-UHFFFAOYSA-N 0.000 description 2
- XOLSOWZOQYJMEW-UHFFFAOYSA-N (4-chlorophenyl)methyl 4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)OCC=2C=CC(Cl)=CC=2)CC1 XOLSOWZOQYJMEW-UHFFFAOYSA-N 0.000 description 2
- FRPMXEMJSCVWMO-UHFFFAOYSA-N (4-cyclopropylphenyl)methyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound C1CC(CN)CCN1C(=O)OCC1=CC=C(C2CC2)C=C1 FRPMXEMJSCVWMO-UHFFFAOYSA-N 0.000 description 2
- YBGWTKMFWGDCNJ-UHFFFAOYSA-N (4-fluorophenyl)methyl 4-[(pyridazin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1=CC(F)=CC=C1COC(=O)N1CCC(CNC=2C=NN=CC=2)CC1 YBGWTKMFWGDCNJ-UHFFFAOYSA-N 0.000 description 2
- IQBMPJYFQVSHLG-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CNC=2N=CC=CN=2)CC1 IQBMPJYFQVSHLG-UHFFFAOYSA-N 0.000 description 2
- UNSLHOHOTVLGIT-UHFFFAOYSA-N (4-methylphenyl)methyl hydrogen carbonate Chemical compound CC1=CC=C(COC(O)=O)C=C1 UNSLHOHOTVLGIT-UHFFFAOYSA-N 0.000 description 2
- IOUDZAFBPDDAMK-AATRIKPKSA-N (e)-3-(2-fluorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1F IOUDZAFBPDDAMK-AATRIKPKSA-N 0.000 description 2
- LPUURRVXQCVXCX-UHFFFAOYSA-N 1-(2-chloroethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCCl)C=C1 LPUURRVXQCVXCX-UHFFFAOYSA-N 0.000 description 2
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 2
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- URTPNQRAHXRPMP-UHFFFAOYSA-N 1-phenylmethoxycarbonylpiperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(=O)OCC1=CC=CC=C1 URTPNQRAHXRPMP-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- VTFVHSUWHOQRTQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-yl 4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=NC=CN=C1NCC1CCN(C(=O)OC2CC3=CC=CC=C3C2)CC1 VTFVHSUWHOQRTQ-UHFFFAOYSA-N 0.000 description 2
- YPVFLPWWOHVBBO-UHFFFAOYSA-N 2-(4-fluorophenyl)ethanesulfonyl chloride Chemical compound FC1=CC=C(CCS(Cl)(=O)=O)C=C1 YPVFLPWWOHVBBO-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- BGLLZQRUXJGTAD-UHFFFAOYSA-N 2-chloro-5-ethylpyrimidine Chemical compound CCC1=CN=C(Cl)N=C1 BGLLZQRUXJGTAD-UHFFFAOYSA-N 0.000 description 2
- KZUYORBGLRMMIR-UHFFFAOYSA-N 2-chloro-5-methyl-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrimidin-4-amine Chemical compound CC1=CN=C(Cl)N=C1NCC1CCN(S(=O)(=O)CCC=2C=CC=CC=2)CC1 KZUYORBGLRMMIR-UHFFFAOYSA-N 0.000 description 2
- JBMBVWROWJGFMG-UHFFFAOYSA-N 2-chloro-7h-purine Chemical compound ClC1=NC=C2NC=NC2=N1 JBMBVWROWJGFMG-UHFFFAOYSA-N 0.000 description 2
- AHDDRJBFJBDEPW-UHFFFAOYSA-N 2-phenylcyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1C1=CC=CC=C1 AHDDRJBFJBDEPW-UHFFFAOYSA-N 0.000 description 2
- GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 2
- XUZGEJZMUUWENN-UHFFFAOYSA-N 3-(piperidin-4-ylmethylamino)-1h-pyrazin-2-one Chemical compound OC1=NC=CN=C1NCC1CCNCC1 XUZGEJZMUUWENN-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- LWAWOVKKJKSAAW-UHFFFAOYSA-N 3-chloro-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrazin-2-amine Chemical compound ClC1=NC=CN=C1NCC1CCN(S(=O)(=O)CCC=2C=CC=CC=2)CC1 LWAWOVKKJKSAAW-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- SBAVBMPTXGQEHD-UHFFFAOYSA-N 4-[(pyridin-4-ylamino)methyl]piperidin-3-ol Chemical compound OC1CNCCC1CNC1=CC=NC=C1 SBAVBMPTXGQEHD-UHFFFAOYSA-N 0.000 description 2
- RODITCQJCJCUNW-UHFFFAOYSA-N 4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1CNC1=NC=C(F)C=N1 RODITCQJCJCUNW-UHFFFAOYSA-N 0.000 description 2
- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
- MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 2
- IGIRTCCCRNZFSQ-UHFFFAOYSA-N 4-chloro-2-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC=C(C#N)C(Cl)=N1 IGIRTCCCRNZFSQ-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 description 2
- KEQDGKORLNMAFN-UHFFFAOYSA-N 5-methyl-n-(piperidin-4-ylmethyl)pyrimidin-2-amine Chemical compound N1=CC(C)=CN=C1NCC1CCNCC1 KEQDGKORLNMAFN-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- REWNFUQNKNDSSJ-UHFFFAOYSA-N C1=C[N+]([O-])=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 Chemical compound C1=C[N+]([O-])=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 REWNFUQNKNDSSJ-UHFFFAOYSA-N 0.000 description 2
- WQMLFEMIZBHHKO-UHFFFAOYSA-N C1CN(CCC1(C(C2=CC=NC=C2)N)O)C(=O)OCC3=CC=CC=C3 Chemical compound C1CN(CCC1(C(C2=CC=NC=C2)N)O)C(=O)OCC3=CC=CC=C3 WQMLFEMIZBHHKO-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical compound C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 102000014649 NMDA glutamate receptor activity proteins Human genes 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
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 2
- BHWNNEWEQWBZBO-DLBZAZTESA-N [(1r,2r)-2-(2-fluorophenyl)cyclopropyl]-[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C(=CC=CC=2)F)CC1 BHWNNEWEQWBZBO-DLBZAZTESA-N 0.000 description 2
- OIKUKLNNGDBPCI-UHFFFAOYSA-N [2-(2,3-difluorophenyl)cyclopropyl]-[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=C(F)C=CC=2)F)CC1 OIKUKLNNGDBPCI-UHFFFAOYSA-N 0.000 description 2
- BUAWQXSOMWPRFO-UHFFFAOYSA-N [2-(2,6-difluorophenyl)cyclopropyl]-[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=CC=CC=2F)F)CC1 BUAWQXSOMWPRFO-UHFFFAOYSA-N 0.000 description 2
- MJLIQORCCYFILA-LSDHHAIUSA-N [4-(aminomethyl)piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound C1CC(CN)CCN1C(=O)[C@H]1[C@H](C=2C=CC=CC=2)C1 MJLIQORCCYFILA-LSDHHAIUSA-N 0.000 description 2
- KMFQVOGSRLZEHM-ZWKOTPCHSA-N [4-[[(3-methoxypyrazin-2-yl)amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound COC1=NC=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 KMFQVOGSRLZEHM-ZWKOTPCHSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
- DXCWGHMFYFZXMJ-IAGOWNOFSA-N benzyl (3s,4r)-3-hydroxy-4-[(pyridin-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C([C@H]1CCN(C[C@H]1O)C(=O)OCC=1C=CC=CC=1)NC1=CC=CC=N1 DXCWGHMFYFZXMJ-IAGOWNOFSA-N 0.000 description 2
- RFMDNYSGEQPCAA-UHFFFAOYSA-N benzyl 3-carbamoylpyrrolidine-1-carboxylate Chemical compound C1C(C(=O)N)CCN1C(=O)OCC1=CC=CC=C1 RFMDNYSGEQPCAA-UHFFFAOYSA-N 0.000 description 2
- GYSTVZNTRDGINE-UHFFFAOYSA-N benzyl 3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound C1C(O)C(CO)CCN1C(=O)OCC1=CC=CC=C1 GYSTVZNTRDGINE-UHFFFAOYSA-N 0.000 description 2
- DJWFEEOFHKXWDG-UHFFFAOYSA-N benzyl 3-hydroxy-4-[[(2,3,5,6-tetrachloropyridin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound OC1CN(C(=O)OCC=2C=CC=CC=2)CCC1CNC1=C(Cl)C(Cl)=NC(Cl)=C1Cl DJWFEEOFHKXWDG-UHFFFAOYSA-N 0.000 description 2
- ZCXLJOFKDFSSNB-UHFFFAOYSA-N benzyl 4-[(7h-purin-6-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C=3N=CNC=3N=CN=2)CCN1C(=O)OCC1=CC=CC=C1 ZCXLJOFKDFSSNB-UHFFFAOYSA-N 0.000 description 2
- GNTKOOLQTGBHAZ-UHFFFAOYSA-N benzyl 4-[[(1-methylimidazol-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CN1C=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 GNTKOOLQTGBHAZ-UHFFFAOYSA-N 0.000 description 2
- ICROQARICORQGF-UHFFFAOYSA-N benzyl 4-[[(2,5,6-trichloropyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=NC(Cl)=C(Cl)C(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 ICROQARICORQGF-UHFFFAOYSA-N 0.000 description 2
- YZGCXTULWZSMTD-UHFFFAOYSA-N benzyl 4-[[(2-amino-6-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound NC1=NC(C)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 YZGCXTULWZSMTD-UHFFFAOYSA-N 0.000 description 2
- OKZKNPHHOTVLOX-UHFFFAOYSA-N benzyl 4-[[(2-oxo-1h-pyrazin-3-yl)amino]methyl]piperidine-1-carboxylate Chemical compound OC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 OKZKNPHHOTVLOX-UHFFFAOYSA-N 0.000 description 2
- ZFNACXWPYYRXBQ-UHFFFAOYSA-N benzyl 4-[[(3-bromopyridin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound BrC1=CN=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 ZFNACXWPYYRXBQ-UHFFFAOYSA-N 0.000 description 2
- DGVHZCZZRDSNBX-UHFFFAOYSA-N benzyl 4-[[(3-cyanopyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C(=NC=CN=2)C#N)CCN1C(=O)OCC1=CC=CC=C1 DGVHZCZZRDSNBX-UHFFFAOYSA-N 0.000 description 2
- DWXKWYKLQVQGSK-UHFFFAOYSA-N benzyl 4-[[(3-fluoropyridin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1=CN=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 DWXKWYKLQVQGSK-UHFFFAOYSA-N 0.000 description 2
- CUDMSIXEWRWCTI-UHFFFAOYSA-N benzyl 4-[[(3-hydroxypyridin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound OC1=CN=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 CUDMSIXEWRWCTI-UHFFFAOYSA-N 0.000 description 2
- FPSTWVWFPSFHNT-UHFFFAOYSA-N benzyl 4-[[(3-methoxy-5-methylpyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC(C)=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 FPSTWVWFPSFHNT-UHFFFAOYSA-N 0.000 description 2
- LLWGCCBKRWHUID-UHFFFAOYSA-N benzyl 4-[[(4,5-dimethylpyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=C(C)C(C)=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 LLWGCCBKRWHUID-UHFFFAOYSA-N 0.000 description 2
- LKSFVUGRVRIQIX-UHFFFAOYSA-N benzyl 4-[[(4-methylpyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CC=NC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 LKSFVUGRVRIQIX-UHFFFAOYSA-N 0.000 description 2
- DNVRRSOLMQIBTG-UHFFFAOYSA-N benzyl 4-[[(5-chloropyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=CN=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 DNVRRSOLMQIBTG-UHFFFAOYSA-N 0.000 description 2
- KNHDHJNMSRKBON-UHFFFAOYSA-N benzyl 4-[[(5-cyano-3-methoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC(C#N)=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 KNHDHJNMSRKBON-UHFFFAOYSA-N 0.000 description 2
- SRNPRWHPOQRSPS-UHFFFAOYSA-N benzyl 4-[[(5-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CN=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 SRNPRWHPOQRSPS-UHFFFAOYSA-N 0.000 description 2
- TWCQMIJBMOOKRY-UHFFFAOYSA-N benzyl 4-[[[2-(dimethylcarbamoyl)pyridin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1=NC(C(=O)N(C)C)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 TWCQMIJBMOOKRY-UHFFFAOYSA-N 0.000 description 2
- RZGLPYBFLXKWQT-UHFFFAOYSA-N benzyl 4-[[[2-[(2,4-dimethoxyphenyl)methylamino]-6-methylpyrimidin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound COC1=CC(OC)=CC=C1CNC1=NC(C)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 RZGLPYBFLXKWQT-UHFFFAOYSA-N 0.000 description 2
- NQWAZLXVKIGVTF-UHFFFAOYSA-N benzyl 4-[[[2-[(dimethylamino)methyl]pyridin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1=NC(CN(C)C)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 NQWAZLXVKIGVTF-UHFFFAOYSA-N 0.000 description 2
- UDZZMUFXRDGZBT-UHFFFAOYSA-N benzyl 4-[[[5-chloro-2,6-bis(methylsulfanyl)pyrimidin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound CSC1=NC(SC)=NC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1Cl UDZZMUFXRDGZBT-UHFFFAOYSA-N 0.000 description 2
- RHKBVLNTAHWVSX-UHFFFAOYSA-N benzyl n-(piperidin-4-ylmethyl)carbamate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1COC(=O)NCC1CCNCC1 RHKBVLNTAHWVSX-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 210000004556 brain Anatomy 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- GJYVOSIUBYVYFI-UHFFFAOYSA-N methyl 2-(2-fluorophenyl)cyclopropane-1-carboxylate Chemical compound COC(=O)C1CC1C1=CC=CC=C1F GJYVOSIUBYVYFI-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- YWUZRPGTMUYDJQ-UHFFFAOYSA-N n-[[1-[2-(4-fluorophenyl)ethylsulfonyl]piperidin-4-yl]methyl]pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1CCS(=O)(=O)N1CCC(CNC=2N=CC=CN=2)CC1 YWUZRPGTMUYDJQ-UHFFFAOYSA-N 0.000 description 2
- ZSPHWEDVYIKZLF-UHFFFAOYSA-N n-benzyl-4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxamide Chemical compound ClC1=NC=CN=C1NCC1CCN(C(=O)NCC=2C=CC=CC=2)CC1 ZSPHWEDVYIKZLF-UHFFFAOYSA-N 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- APXBXAJWVZTKSE-UHFFFAOYSA-N pyridine-2,3,4-triamine Chemical compound NC1=CC=NC(N)=C1N APXBXAJWVZTKSE-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical compound OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- CWTOBKKLDAHQCO-BQYQJAHWSA-N tert-butyl (e)-3-(5-methylthiophen-2-yl)prop-2-enoate Chemical compound CC1=CC=C(\C=C\C(=O)OC(C)(C)C)S1 CWTOBKKLDAHQCO-BQYQJAHWSA-N 0.000 description 2
- LHJZQQDQPDWNNI-UHFFFAOYSA-N tert-butyl 4-(phenylmethoxycarbonylaminomethyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC(=O)OCC1=CC=CC=C1 LHJZQQDQPDWNNI-UHFFFAOYSA-N 0.000 description 2
- HFVAAUFXDRJCGO-UHFFFAOYSA-N tert-butyl 4-[1-(pyridin-4-ylamino)ethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(C)NC1=CC=NC=C1 HFVAAUFXDRJCGO-UHFFFAOYSA-N 0.000 description 2
- IPYZOWMKVFBXME-UHFFFAOYSA-N tert-butyl 4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC1=NC=CN=C1Cl IPYZOWMKVFBXME-UHFFFAOYSA-N 0.000 description 2
- YQRHFEWOFANIIT-UHFFFAOYSA-N tert-butyl 4-[[(3-methoxy-5-methylpyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC(C)=CN=C1NCC1CCN(C(=O)OC(C)(C)C)CC1 YQRHFEWOFANIIT-UHFFFAOYSA-N 0.000 description 2
- UPWCWGOVSNBJIN-UHFFFAOYSA-N tert-butyl n-[[1-[2-(4-fluorophenyl)ethylsulfonyl]piperidin-4-yl]methyl]carbamate Chemical compound C1CC(CNC(=O)OC(C)(C)C)CCN1S(=O)(=O)CCC1=CC=C(F)C=C1 UPWCWGOVSNBJIN-UHFFFAOYSA-N 0.000 description 2
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UKHQRARQNZOXRL-UHFFFAOYSA-N trimethyltin Chemical compound C[SnH](C)C UKHQRARQNZOXRL-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- ALIVUKPICDOVPV-PHDIDXHHSA-N (1R,2R)-2-(2,6-difluorophenyl)cyclopropane-1-carboxylic acid Chemical compound FC1=C(C(=CC=C1)F)[C@H]1[C@@H](C1)C(=O)O ALIVUKPICDOVPV-PHDIDXHHSA-N 0.000 description 1
- OLDXGEXZLWOGJN-JGVFFNPUSA-N (1r,2r)-2-(2-fluorophenyl)cyclopropane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1C[C@H]1C1=CC=CC=C1F OLDXGEXZLWOGJN-JGVFFNPUSA-N 0.000 description 1
- QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 1
- RJYCRZJIAWUORY-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) (4-fluorophenyl)methyl carbonate Chemical compound C1=CC(F)=CC=C1COC(=O)ON1C(=O)CCC1=O RJYCRZJIAWUORY-UHFFFAOYSA-N 0.000 description 1
- AAEQHNIOTYFQBZ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) (4-propan-2-ylphenyl)methyl carbonate Chemical compound C1=CC(C(C)C)=CC=C1COC(=O)ON1C(=O)CCC1=O AAEQHNIOTYFQBZ-UHFFFAOYSA-N 0.000 description 1
- BPFHKNAHFXQEMM-UHFFFAOYSA-N (2-phenylcyclopropyl)-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]methanone Chemical compound C1CC(CNC=2N=CC=CN=2)CCN1C(=O)C1CC1C1=CC=CC=C1 BPFHKNAHFXQEMM-UHFFFAOYSA-N 0.000 description 1
- XXNXSJXYMLULSA-UHFFFAOYSA-N (3-methylphenyl)methyl 4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound CC1=CC=CC(COC(=O)N2CCC(CNC=3C=CN=CC=3)CC2)=C1 XXNXSJXYMLULSA-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- GXOYHADTONLQHF-MWLCHTKSSA-N (3s,4r)-3-hydroxy-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylic acid Chemical compound O[C@@H]1CN(C(O)=O)CC[C@@H]1CNC1=CC=NC=C1 GXOYHADTONLQHF-MWLCHTKSSA-N 0.000 description 1
- GFZRDVDHXJKBRL-UHFFFAOYSA-N (4-chlorophenyl)methyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound C1=CC(Cl)=CC=C1COC(=O)ON1C(=O)CCC1=O GFZRDVDHXJKBRL-UHFFFAOYSA-N 0.000 description 1
- DOPDVNGFOXYWNG-UHFFFAOYSA-N (4-chlorophenyl)methyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound C1CC(CN)CCN1C(=O)OCC1=CC=C(Cl)C=C1 DOPDVNGFOXYWNG-UHFFFAOYSA-N 0.000 description 1
- FKVJCBDSAQEXLV-UHFFFAOYSA-N (4-chlorophenyl)methyl 4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(Cl)=CC=C1COC(=O)N1CCC(CNC=2C(=NC=CN=2)Cl)CC1 FKVJCBDSAQEXLV-UHFFFAOYSA-N 0.000 description 1
- NSKBUOOMPYQVFP-UHFFFAOYSA-N (4-chlorophenyl)methyl 4-[[(3-methylpyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CC=CN=C1NCC1CCN(C(=O)OCC=2C=CC(Cl)=CC=2)CC1 NSKBUOOMPYQVFP-UHFFFAOYSA-N 0.000 description 1
- JIOZURUGBGWRKN-UHFFFAOYSA-N (4-chlorophenyl)methyl 4-[[(5-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CN=CN=C1NCC1CCN(C(=O)OCC=2C=CC(Cl)=CC=2)CC1 JIOZURUGBGWRKN-UHFFFAOYSA-N 0.000 description 1
- LDBXTMQUMIIQSX-UYAOXDASSA-N (4-ethylphenyl)methyl (3s,4r)-3-hydroxy-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1=CC(CC)=CC=C1COC(=O)N1C[C@@H](O)[C@@H](CNC=2C=CN=CC=2)CC1 LDBXTMQUMIIQSX-UYAOXDASSA-N 0.000 description 1
- VVXDDDUMKLWPQN-UHFFFAOYSA-N (4-fluorophenyl)methyl 4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(F)=CC=C1COC(=O)N1CCC(CNC=2C(=NC=CN=2)Cl)CC1 VVXDDDUMKLWPQN-UHFFFAOYSA-N 0.000 description 1
- OVCNVKITMVTUJX-UHFFFAOYSA-N (4-fluorophenyl)methyl 4-[[(3-methylpyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CC=CN=C1NCC1CCN(C(=O)OCC=2C=CC(F)=CC=2)CC1 OVCNVKITMVTUJX-UHFFFAOYSA-N 0.000 description 1
- USXDYJJIZXDGPX-UHFFFAOYSA-N (4-fluorophenyl)methyl 4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(F)=CC=C1COC(=O)N1CCC(CNC=2N=CC(F)=CN=2)CC1 USXDYJJIZXDGPX-UHFFFAOYSA-N 0.000 description 1
- BNWMWOSMWKBAQA-UHFFFAOYSA-N (4-fluorophenyl)methyl 4-[[(5-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CN=CN=C1NCC1CCN(C(=O)OCC=2C=CC(F)=CC=2)CC1 BNWMWOSMWKBAQA-UHFFFAOYSA-N 0.000 description 1
- BAZJFDNZEWVICL-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(3-chloropyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CNC=2C(=NC=CN=2)Cl)CC1 BAZJFDNZEWVICL-UHFFFAOYSA-N 0.000 description 1
- MUOBBUUUVCUJGG-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(3-methoxy-5-methylpyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC(C)=CN=C1NCC1CCN(C(=O)OCC=2C=CC(C)=CC=2)CC1 MUOBBUUUVCUJGG-UHFFFAOYSA-N 0.000 description 1
- VIDWXEWXHTWNRK-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(3-methoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC(C)=CC=2)CC1 VIDWXEWXHTWNRK-UHFFFAOYSA-N 0.000 description 1
- RQZLVAJWRPRZSK-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(3-methylpyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CNC=2C(=CC=CN=2)C)CC1 RQZLVAJWRPRZSK-UHFFFAOYSA-N 0.000 description 1
- XXCITNRMOFFDJD-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(4,5-dimethylpyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CNC=2N=C(C)C(C)=CN=2)CC1 XXCITNRMOFFDJD-UHFFFAOYSA-N 0.000 description 1
- YJPXXVRMIJRLOX-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CNC=2N=CC(F)=CN=2)CC1 YJPXXVRMIJRLOX-UHFFFAOYSA-N 0.000 description 1
- HLTHLTWHLZBLIW-UHFFFAOYSA-N (4-methylphenyl)methyl 4-[[(5-methylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1COC(=O)N1CCC(CNC=2C(=CN=CN=2)C)CC1 HLTHLTWHLZBLIW-UHFFFAOYSA-N 0.000 description 1
- IRKOZGUDGGFSRE-UHFFFAOYSA-N (5-chloro-6-methoxypyridin-3-yl)methanol Chemical compound COC1=NC=C(CO)C=C1Cl IRKOZGUDGGFSRE-UHFFFAOYSA-N 0.000 description 1
- ONWRSBMOCIQLRK-VOTSOKGWSA-N (e)-2-phenylethenesulfonyl chloride Chemical compound ClS(=O)(=O)\C=C\C1=CC=CC=C1 ONWRSBMOCIQLRK-VOTSOKGWSA-N 0.000 description 1
- NVQHKPLMLCHFSU-SNAWJCMRSA-N (e)-3-(2,3-difluorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(F)=C1F NVQHKPLMLCHFSU-SNAWJCMRSA-N 0.000 description 1
- JMUOYANNVIFGFN-SNAWJCMRSA-N (e)-3-(2,6-difluorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=C(F)C=CC=C1F JMUOYANNVIFGFN-SNAWJCMRSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- RHFWLPWDOYJEAL-UHFFFAOYSA-N 1,2-oxazol-3-amine Chemical compound NC=1C=CON=1 RHFWLPWDOYJEAL-UHFFFAOYSA-N 0.000 description 1
- QUKGLNCXGVWCJX-UHFFFAOYSA-N 1,3,4-thiadiazol-2-amine Chemical compound NC1=NN=CS1 QUKGLNCXGVWCJX-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
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- PCJZXBBOMORHMN-UHFFFAOYSA-N 1-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]-4-thiophen-2-ylbutan-1-one Chemical compound C1CC(CNC=2N=CC=CN=2)CCN1C(=O)CCCC1=CC=CS1 PCJZXBBOMORHMN-UHFFFAOYSA-N 0.000 description 1
- XQRLXUYZKZXSBN-UHFFFAOYSA-N 1-benzyl-4-hydroxypiperidine-4-carbonitrile Chemical compound C1CC(O)(C#N)CCN1CC1=CC=CC=C1 XQRLXUYZKZXSBN-UHFFFAOYSA-N 0.000 description 1
- NZVZVGPYTICZBZ-UHFFFAOYSA-N 1-benzylpiperidine Chemical class C=1C=CC=CC=1CN1CCCCC1 NZVZVGPYTICZBZ-UHFFFAOYSA-N 0.000 description 1
- YNQXOOPPJWSXMW-UHFFFAOYSA-N 1-ethenyl-2-fluorobenzene Chemical compound FC1=CC=CC=C1C=C YNQXOOPPJWSXMW-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- IWWCCNVRNHTGLV-UHFFFAOYSA-N 1-phenylcyclopropane-1-carboxylic acid Chemical class C=1C=CC=CC=1C1(C(=O)O)CC1 IWWCCNVRNHTGLV-UHFFFAOYSA-N 0.000 description 1
- UOUIKYFLNQXAFR-UHFFFAOYSA-N 1h-benzimidazole;piperidine Chemical class C1CCNCC1.C1=CC=C2NC=NC2=C1 UOUIKYFLNQXAFR-UHFFFAOYSA-N 0.000 description 1
- KUWRLKJYNASPQZ-UHFFFAOYSA-N 1h-imidazol-3-ium-2-amine;sulfate Chemical compound OS(O)(=O)=O.NC1=NC=CN1.NC1=NC=CN1 KUWRLKJYNASPQZ-UHFFFAOYSA-N 0.000 description 1
- UACZEBCMUQWIIC-UHFFFAOYSA-N 2,3,5,6-tetrachloro-4-nitropyridine Chemical compound [O-][N+](=O)C1=C(Cl)C(Cl)=NC(Cl)=C1Cl UACZEBCMUQWIIC-UHFFFAOYSA-N 0.000 description 1
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
- OGVLEPMNNPZAPS-UHFFFAOYSA-N 2,3-difluoropyridine Chemical compound FC1=CC=CN=C1F OGVLEPMNNPZAPS-UHFFFAOYSA-N 0.000 description 1
- XLIMPWDCNIVZOO-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-yl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound C1CC(CN)CCN1C(=O)OC1CC2=CC=CC=C2C1 XLIMPWDCNIVZOO-UHFFFAOYSA-N 0.000 description 1
- GVBHCMNXRKOJRH-UHFFFAOYSA-N 2,4,5,6-tetrachloropyrimidine Chemical compound ClC1=NC(Cl)=C(Cl)C(Cl)=N1 GVBHCMNXRKOJRH-UHFFFAOYSA-N 0.000 description 1
- BTLKROSJMNFSQZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(Cl)=N1 BTLKROSJMNFSQZ-UHFFFAOYSA-N 0.000 description 1
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 1
- TUQSVSYUEBNNKQ-UHFFFAOYSA-N 2,4-dichloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC(Cl)=C21 TUQSVSYUEBNNKQ-UHFFFAOYSA-N 0.000 description 1
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 1
- HNIGZVZDWCTFPR-UHFFFAOYSA-N 2-(2-fluorophenyl)ethanol Chemical compound OCCC1=CC=CC=C1F HNIGZVZDWCTFPR-UHFFFAOYSA-N 0.000 description 1
- HZFRKZWBVUJYDA-UHFFFAOYSA-N 2-(4-chlorophenyl)ethanol Chemical compound OCCC1=CC=C(Cl)C=C1 HZFRKZWBVUJYDA-UHFFFAOYSA-N 0.000 description 1
- DAVFJRVIVZOKKS-UHFFFAOYSA-N 2-(4-methylphenyl)ethanol Chemical compound CC1=CC=C(CCO)C=C1 DAVFJRVIVZOKKS-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- XAOJTBCPDTYREH-UHFFFAOYSA-N 2-[(2-methylphenyl)methyl]-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylic acid Chemical compound CC1=CC=CC=C1CC2CC(CCN2C(=O)O)CNC3=CC=NC=C3 XAOJTBCPDTYREH-UHFFFAOYSA-N 0.000 description 1
- NYPGNLRUKIUUCK-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylic acid Chemical compound COC1=CC=C(C=C1)CC2CC(CCN2C(=O)O)CNC3=CC=NC=C3 NYPGNLRUKIUUCK-UHFFFAOYSA-N 0.000 description 1
- OFAVQWMHOSEDHQ-UHFFFAOYSA-N 2-[(4-methylphenyl)methyl]-4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylic acid Chemical compound CC1=CC=C(C=C1)CC2CC(CCN2C(=O)O)CNC3=CC=NC=C3 OFAVQWMHOSEDHQ-UHFFFAOYSA-N 0.000 description 1
- DZPRZMLFWQZHIR-UHFFFAOYSA-N 2-[(4-methylphenyl)methyl]-4-[[(3-methylpyridin-2-yl)amino]methyl]piperidine-1-carboxylic acid Chemical compound C1=CC(C)=CC=C1CC1N(C(O)=O)CCC(CNC=2C(=CC=CN=2)C)C1 DZPRZMLFWQZHIR-UHFFFAOYSA-N 0.000 description 1
- VDSISXHVUFTMPB-UHFFFAOYSA-N 2-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methylamino]pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(NCC2CCN(CC2)S(=O)(=O)CCC=2C=CC=CC=2)=N1 VDSISXHVUFTMPB-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- RXATZPCCMYMPME-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1Cl RXATZPCCMYMPME-UHFFFAOYSA-N 0.000 description 1
- BHAKRVSCGILCEW-UHFFFAOYSA-N 2-chloro-4-methylpyrimidine Chemical compound CC1=CC=NC(Cl)=N1 BHAKRVSCGILCEW-UHFFFAOYSA-N 0.000 description 1
- SLQAJWTZUXJPNY-UHFFFAOYSA-N 2-chloro-5-fluoropyrimidin-4-amine Chemical compound NC1=NC(Cl)=NC=C1F SLQAJWTZUXJPNY-UHFFFAOYSA-N 0.000 description 1
- LPBDZVNGCNTELM-UHFFFAOYSA-N 2-chloropyrimidin-4-amine Chemical compound NC1=CC=NC(Cl)=N1 LPBDZVNGCNTELM-UHFFFAOYSA-N 0.000 description 1
- UXXQEVFRPLIOHJ-UHFFFAOYSA-N 2-chloropyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(Cl)=N1 UXXQEVFRPLIOHJ-UHFFFAOYSA-N 0.000 description 1
- YMDSUQSBJRDYLI-UHFFFAOYSA-N 2-chloropyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Cl)=N1 YMDSUQSBJRDYLI-UHFFFAOYSA-N 0.000 description 1
- JBVSBLLOZVDAAZ-UHFFFAOYSA-N 2-diazonio-1-[(2-methylpropan-2-yl)oxy]ethenolate Chemical compound CC(C)(C)OC([O-])=C[N+]#N JBVSBLLOZVDAAZ-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- XTLKENCFQIAAJK-UHFFFAOYSA-N 2-methylsulfanyl-6-oxo-1h-pyrimidine-5-carbonitrile Chemical compound CSC1=NC=C(C#N)C(=O)N1 XTLKENCFQIAAJK-UHFFFAOYSA-N 0.000 description 1
- FOEMIZSFFWGXHX-UHFFFAOYSA-N 2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC=N1 FOEMIZSFFWGXHX-UHFFFAOYSA-N 0.000 description 1
- NCVUCROTSCMJDI-UHFFFAOYSA-N 2-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC=C(C#N)C=N1 NCVUCROTSCMJDI-UHFFFAOYSA-N 0.000 description 1
- WUVXASKPNIDGCY-UHFFFAOYSA-N 2-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(NCC2CCN(CC2)S(=O)(=O)CCC=2C=CC=CC=2)=N1 WUVXASKPNIDGCY-UHFFFAOYSA-N 0.000 description 1
- NENUDJUGKNWWAD-UHFFFAOYSA-N 2-phenoxy-1-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]ethanone Chemical compound C1CC(CNC=2N=CC=CN=2)CCN1C(=O)COC1=CC=CC=C1 NENUDJUGKNWWAD-UHFFFAOYSA-N 0.000 description 1
- GBAOOJAWDCNOGO-UHFFFAOYSA-N 3,4,5-trichloropyridazine Chemical compound ClC1=CN=NC(Cl)=C1Cl GBAOOJAWDCNOGO-UHFFFAOYSA-N 0.000 description 1
- ZFZWZGANFCWADD-UHFFFAOYSA-N 3,4-dibromopyridine Chemical compound BrC1=CC=NC=C1Br ZFZWZGANFCWADD-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- DBDKLFOUWUHPDW-UHFFFAOYSA-N 3-Hydroxy-4-aminopyridine Chemical compound NC1=CC=NC=C1O DBDKLFOUWUHPDW-UHFFFAOYSA-N 0.000 description 1
- BOWIFWCBNWWZOG-UHFFFAOYSA-N 3-Thiophenemethanol Chemical compound OCC=1C=CSC=1 BOWIFWCBNWWZOG-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- SDLFAEGTVBPHBK-UHFFFAOYSA-N 3-chloropyrazine-2-carbonitrile Chemical compound ClC1=NC=CN=C1C#N SDLFAEGTVBPHBK-UHFFFAOYSA-N 0.000 description 1
- MSLUTDVOKZOXTA-UHFFFAOYSA-N 3-fluoro-4-iodopyridine Chemical compound FC1=CN=CC=C1I MSLUTDVOKZOXTA-UHFFFAOYSA-N 0.000 description 1
- RRRCPCOJPQLWEP-UHFFFAOYSA-N 3-hydroxytriazolo[4,5-b]pyridine Chemical compound C1=CN=C2N(O)N=NC2=C1.C1=CN=C2N(O)N=NC2=C1 RRRCPCOJPQLWEP-UHFFFAOYSA-N 0.000 description 1
- AWXAYVJIWODHCH-UHFFFAOYSA-N 3-methyl-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrazin-2-amine Chemical compound CC1=NC=CN=C1NCC1CCN(S(=O)(=O)CCC=2C=CC=CC=2)CC1 AWXAYVJIWODHCH-UHFFFAOYSA-N 0.000 description 1
- RGDQRXPEZUNWHX-UHFFFAOYSA-N 3-methylpyridin-2-amine Chemical compound CC1=CC=CN=C1N RGDQRXPEZUNWHX-UHFFFAOYSA-N 0.000 description 1
- VGJLGPCXUGIXRQ-UHFFFAOYSA-N 3-methylpyridin-4-amine Chemical compound CC1=CN=CC=C1N VGJLGPCXUGIXRQ-UHFFFAOYSA-N 0.000 description 1
- IOCXBXZBNOYTLQ-UHFFFAOYSA-N 3-nitrobenzene-1,2-diamine Chemical compound NC1=CC=CC([N+]([O-])=O)=C1N IOCXBXZBNOYTLQ-UHFFFAOYSA-N 0.000 description 1
- VKCFTTCFIPFHON-UHFFFAOYSA-N 3-phenyl-1-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]propan-1-one Chemical compound C1CC(CNC=2N=CC=CN=2)CCN1C(=O)CCC1=CC=CC=C1 VKCFTTCFIPFHON-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- VJWXIRQLLGYIDI-UHFFFAOYSA-N 4,5-dichloro-1h-pyridazin-6-one Chemical compound OC1=NN=CC(Cl)=C1Cl VJWXIRQLLGYIDI-UHFFFAOYSA-N 0.000 description 1
- IOSUEOLOSZOHDE-UHFFFAOYSA-N 4,5-dichloropyridazine Chemical compound ClC1=CN=NC=C1Cl IOSUEOLOSZOHDE-UHFFFAOYSA-N 0.000 description 1
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 1
- CUVGUPIVTLGRGI-UHFFFAOYSA-N 4-(3-phosphonopropyl)piperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCP(O)(O)=O)CCN1 CUVGUPIVTLGRGI-UHFFFAOYSA-N 0.000 description 1
- IWYHVVSOLJTLRK-UHFFFAOYSA-N 4-(aminomethyl)-1-benzylpiperidin-4-ol Chemical compound C1CC(CN)(O)CCN1CC1=CC=CC=C1 IWYHVVSOLJTLRK-UHFFFAOYSA-N 0.000 description 1
- MZRGNMWEURVQHC-UHFFFAOYSA-N 4-(aminomethyl)-n-benzylpiperidine-1-carboxamide Chemical compound C1CC(CN)CCN1C(=O)NCC1=CC=CC=C1 MZRGNMWEURVQHC-UHFFFAOYSA-N 0.000 description 1
- ZXPDVRCLICXEDW-UHFFFAOYSA-N 4-(aminomethyl)piperidine-1-carboxylic acid Chemical compound NCC1CCN(C(O)=O)CC1 ZXPDVRCLICXEDW-UHFFFAOYSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- BBGQDCUYNPDMLU-UHFFFAOYSA-N 4-[[(2-methylsulfanylpyrimidin-4-yl)amino]methyl]piperidine-1-carboxylic acid Chemical compound CSC1=NC=CC(NCC2CCN(CC2)C(O)=O)=N1 BBGQDCUYNPDMLU-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- VORVXWYMJOCGAY-UHFFFAOYSA-N 4-[[[2-[(2,4-dimethoxyphenyl)methylamino]-6-methylpyrimidin-4-yl]amino]methyl]piperidine-1-carboxylic acid Chemical compound COC1=CC(OC)=CC=C1CNC1=NC(C)=CC(NCC2CCN(CC2)C(O)=O)=N1 VORVXWYMJOCGAY-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
- DFOHHQRGDOQMKG-UHFFFAOYSA-N 4-chloro-2-methylsulfanylpyrimidine Chemical group CSC1=NC=CC(Cl)=N1 DFOHHQRGDOQMKG-UHFFFAOYSA-N 0.000 description 1
- BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- PVMNPAUTCMBOMO-UHFFFAOYSA-N 4-chloropyridine Chemical compound ClC1=CC=NC=C1 PVMNPAUTCMBOMO-UHFFFAOYSA-N 0.000 description 1
- NNMYRMGMVLMQAY-UHFFFAOYSA-N 4-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC=N1 NNMYRMGMVLMQAY-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- SJWHILBZPGQBJE-UHFFFAOYSA-N 4-ethylpyridin-2-amine Chemical compound CCC1=CC=NC(N)=C1 SJWHILBZPGQBJE-UHFFFAOYSA-N 0.000 description 1
- MWUVGXCUHWKQJE-UHFFFAOYSA-N 4-fluorophenethyl alcohol Chemical compound OCCC1=CC=C(F)C=C1 MWUVGXCUHWKQJE-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000002528 4-isopropyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- LWSFXJZBVVGVIO-UHFFFAOYSA-N 4-methyl-2-methylsulfonylpyrimidine Chemical compound CC1=CC=NC(S(C)(=O)=O)=N1 LWSFXJZBVVGVIO-UHFFFAOYSA-N 0.000 description 1
- KIUQAXPDSDMBAD-UHFFFAOYSA-N 4-methyl-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrimidin-2-amine Chemical compound CC1=CC=NC(NCC2CCN(CC2)S(=O)(=O)CCC=2C=CC=CC=2)=N1 KIUQAXPDSDMBAD-UHFFFAOYSA-N 0.000 description 1
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 1
- ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
- NEJMFSBXFBFELK-UHFFFAOYSA-N 4-nitro-1h-benzimidazole Chemical compound [O-][N+](=O)C1=CC=CC2=C1N=CN2 NEJMFSBXFBFELK-UHFFFAOYSA-N 0.000 description 1
- VAUMDUIUEPIGHM-UHFFFAOYSA-N 5-Methyl-2-thiophenecarboxaldehyde Chemical compound CC1=CC=C(C=O)S1 VAUMDUIUEPIGHM-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- BHVVGKNWWUCNHC-UHFFFAOYSA-N 5-fluoro-n-(piperidin-4-ylmethyl)pyrimidin-2-amine Chemical compound N1=CC(F)=CN=C1NCC1CCNCC1 BHVVGKNWWUCNHC-UHFFFAOYSA-N 0.000 description 1
- RMTFEZUZAHJEFW-UHFFFAOYSA-N 5-fluoropyrimidine-2,4-diamine Chemical group NC1=NC=C(F)C(N)=N1 RMTFEZUZAHJEFW-UHFFFAOYSA-N 0.000 description 1
- RREVRBVRAXKKHC-UHFFFAOYSA-N 5-methyl-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrimidin-4-amine Chemical compound CC1=CN=CN=C1NCC1CCN(S(=O)(=O)CCC=2C=CC=CC=2)CC1 RREVRBVRAXKKHC-UHFFFAOYSA-N 0.000 description 1
- CMBSSVKZOPZBKW-UHFFFAOYSA-N 5-methylpyridin-2-amine Chemical compound CC1=CC=C(N)N=C1 CMBSSVKZOPZBKW-UHFFFAOYSA-N 0.000 description 1
- WERABQRUGJIMKQ-UHFFFAOYSA-N 6-chloro-3-nitropyridin-2-amine Chemical compound NC1=NC(Cl)=CC=C1[N+]([O-])=O WERABQRUGJIMKQ-UHFFFAOYSA-N 0.000 description 1
- NCZREVPKGQGLFM-UHFFFAOYSA-N 6-chloro-7-methylpurine Chemical compound C1=NC(Cl)=C2N(C)C=NC2=N1 NCZREVPKGQGLFM-UHFFFAOYSA-N 0.000 description 1
- ZOCRUZXAFFVHQH-UHFFFAOYSA-N 6-chloropurin-4-amine Chemical compound ClC1=NC=NC2(N)C1=NC=N2 ZOCRUZXAFFVHQH-UHFFFAOYSA-N 0.000 description 1
- CZPOFSDHJNNWQL-UHFFFAOYSA-N 6-chloropyrazine-2-carbonitrile Chemical compound ClC1=CN=CC(C#N)=N1 CZPOFSDHJNNWQL-UHFFFAOYSA-N 0.000 description 1
- UIIPPFUGTHCXOD-RBUKOAKNSA-N 6-methoxy-5-[[1-[(1r,2r)-2-phenylcyclopropanecarbonyl]piperidin-4-yl]methylamino]pyrazine-2-carbonitrile Chemical compound COC1=NC(C#N)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 UIIPPFUGTHCXOD-RBUKOAKNSA-N 0.000 description 1
- HAWCUEYFSQKISQ-UHFFFAOYSA-N 7-chloro-1h-imidazo[4,5-b]pyridine Chemical compound ClC1=CC=NC2=C1NC=N2 HAWCUEYFSQKISQ-UHFFFAOYSA-N 0.000 description 1
- IOFLMWHNRHZTRF-UHFFFAOYSA-N 7-methyl-n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]purin-6-amine Chemical compound C=12N(C)C=NC2=NC=NC=1NCC(CC1)CCN1S(=O)(=O)CCC1=CC=CC=C1 IOFLMWHNRHZTRF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- BGRGWJFOHPYXBA-UHFFFAOYSA-N C=1C=NC=CC=1C(N)C1CCNCC1O Chemical compound C=1C=NC=CC=1C(N)C1CCNCC1O BGRGWJFOHPYXBA-UHFFFAOYSA-N 0.000 description 1
- YUJFQPCVWOODOH-UHFFFAOYSA-N CC1=C(N=CC=C1)NCC2CCN(C(C2)CC3=CC=C(C=C3)Cl)C(=O)O Chemical compound CC1=C(N=CC=C1)NCC2CCN(C(C2)CC3=CC=C(C=C3)Cl)C(=O)O YUJFQPCVWOODOH-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- ILOBJXUSYAOARJ-UHFFFAOYSA-N ClC1=NC2=CC=CC=C2C(=N1)N.ClC1=NC2=CC=CC=C2C(=N1)N Chemical compound ClC1=NC2=CC=CC=C2C(=N1)N.ClC1=NC2=CC=CC=C2C(=N1)N ILOBJXUSYAOARJ-UHFFFAOYSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100029458 Glutamate receptor ionotropic, NMDA 2A Human genes 0.000 description 1
- 102100022631 Glutamate receptor ionotropic, NMDA 2C Human genes 0.000 description 1
- 102100022626 Glutamate receptor ionotropic, NMDA 2D Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000972850 Homo sapiens Glutamate receptor ionotropic, NMDA 2B Proteins 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-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
- 108091008644 NR2D Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001442654 Percnon planissimum Species 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000025609 Urogenital disease Diseases 0.000 description 1
- OIKUKLNNGDBPCI-JKSUJKDBSA-N [(1r,2r)-2-(2,3-difluorophenyl)cyclopropyl]-[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C(=C(F)C=CC=2)F)CC1 OIKUKLNNGDBPCI-JKSUJKDBSA-N 0.000 description 1
- BUAWQXSOMWPRFO-HUUCEWRRSA-N [(1r,2r)-2-(2,6-difluorophenyl)cyclopropyl]-[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C(=CC=CC=2F)F)CC1 BUAWQXSOMWPRFO-HUUCEWRRSA-N 0.000 description 1
- ATJXIPKYUFXOGZ-UHFFFAOYSA-N [1-[2-(4-fluorophenyl)ethylsulfonyl]piperidin-4-yl]methanamine Chemical compound C1CC(CN)CCN1S(=O)(=O)CCC1=CC=C(F)C=C1 ATJXIPKYUFXOGZ-UHFFFAOYSA-N 0.000 description 1
- QGTHDIYRAWLOSP-UHFFFAOYSA-N [2-(2,3-difluorophenyl)cyclopropyl]-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]methanone Chemical compound FC1=CC=CC(C2C(C2)C(=O)N2CCC(CNC=3N=CC=CN=3)CC2)=C1F QGTHDIYRAWLOSP-UHFFFAOYSA-N 0.000 description 1
- OZPQGOKPQIUXOZ-UHFFFAOYSA-N [2-(2,3-difluorophenyl)cyclopropyl]-[4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(C)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=C(F)C=CC=2)F)CC1 OZPQGOKPQIUXOZ-UHFFFAOYSA-N 0.000 description 1
- TUHBHRGJWZZKCL-UHFFFAOYSA-N [2-(2,6-difluorophenyl)cyclopropyl]-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]methanone Chemical compound FC1=CC=CC(F)=C1C1C(C(=O)N2CCC(CNC=3N=CC=CN=3)CC2)C1 TUHBHRGJWZZKCL-UHFFFAOYSA-N 0.000 description 1
- ZRQQQHAQDQPIJI-UHFFFAOYSA-N [2-(2,6-difluorophenyl)cyclopropyl]-[4-[[(4,5-dimethylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=C(C)C(C)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=CC=CC=2F)F)CC1 ZRQQQHAQDQPIJI-UHFFFAOYSA-N 0.000 description 1
- DDQFJTIKADZTTP-UHFFFAOYSA-N [2-(2,6-difluorophenyl)cyclopropyl]-[4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(C)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=CC=CC=2F)F)CC1 DDQFJTIKADZTTP-UHFFFAOYSA-N 0.000 description 1
- BHWNNEWEQWBZBO-UHFFFAOYSA-N [2-(2-fluorophenyl)cyclopropyl]-[4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=CC=CC=2)F)CC1 BHWNNEWEQWBZBO-UHFFFAOYSA-N 0.000 description 1
- GBLRDXCSNNEMFO-UHFFFAOYSA-N [2-(2-fluorophenyl)cyclopropyl]-[4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(C)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=CC=CC=2)F)CC1 GBLRDXCSNNEMFO-UHFFFAOYSA-N 0.000 description 1
- PZHCDGLLENQQGI-UHFFFAOYSA-N [2-(2-methylphenyl)cyclopropyl]-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC=C1C1C(C(=O)N2CCC(CNC=3N=CC=CN=3)CC2)C1 PZHCDGLLENQQGI-UHFFFAOYSA-N 0.000 description 1
- GWIDMJBLEPFVKG-UHFFFAOYSA-N [2-(2-methylphenyl)cyclopropyl]-[4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound N1=CC(C)=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C(=CC=CC=2)C)CC1 GWIDMJBLEPFVKG-UHFFFAOYSA-N 0.000 description 1
- PQTMXPPIUAGMDB-UHFFFAOYSA-N [2-(3-methylphenyl)cyclopropyl]-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC(C2C(C2)C(=O)N2CCC(CNC=3N=CC=CN=3)CC2)=C1 PQTMXPPIUAGMDB-UHFFFAOYSA-N 0.000 description 1
- QFYOIZCLPODIQF-UHFFFAOYSA-N [2-(3-methylphenyl)cyclopropyl]-[4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC(C2C(C2)C(=O)N2CCC(CNC=3N=CC(C)=CN=3)CC2)=C1 QFYOIZCLPODIQF-UHFFFAOYSA-N 0.000 description 1
- PFAUPCPWPQONTP-UHFFFAOYSA-N [2-(4-methylphenyl)cyclopropyl]-[4-[(pyrimidin-2-ylamino)methyl]piperidin-1-yl]methanone Chemical compound C1=CC(C)=CC=C1C1C(C(=O)N2CCC(CNC=3N=CC=CN=3)CC2)C1 PFAUPCPWPQONTP-UHFFFAOYSA-N 0.000 description 1
- HHDGMNKESNXVRZ-UHFFFAOYSA-N [4-[[(3-fluoropyridin-2-yl)amino]methyl]piperidin-1-yl]-(2-phenylcyclopropyl)methanone Chemical compound FC1=CC=CN=C1NCC1CCN(C(=O)C2C(C2)C=2C=CC=CC=2)CC1 HHDGMNKESNXVRZ-UHFFFAOYSA-N 0.000 description 1
- CPUZCWFGYDSVSI-VQTJNVASSA-N [4-[[(4,5-dimethylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound N1=C(C)C(C)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 CPUZCWFGYDSVSI-VQTJNVASSA-N 0.000 description 1
- DPAGQPOQJNPIQQ-ZWKOTPCHSA-N [4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound N1=CC(F)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 DPAGQPOQJNPIQQ-ZWKOTPCHSA-N 0.000 description 1
- PPFQPIASLDVUJB-UHFFFAOYSA-N [4-[[(5-fluoropyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[2-(3-methylphenyl)cyclopropyl]methanone Chemical compound CC1=CC=CC(C2C(C2)C(=O)N2CCC(CNC=3N=CC(F)=CN=3)CC2)=C1 PPFQPIASLDVUJB-UHFFFAOYSA-N 0.000 description 1
- QSCWNZDWGMTSGO-RBUKOAKNSA-N [4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound N1=CC(C)=CN=C1NCC1CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 QSCWNZDWGMTSGO-RBUKOAKNSA-N 0.000 description 1
- DQBNHVGZLDSTOB-UHFFFAOYSA-N [4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[2-(5-methylthiophen-2-yl)cyclopropyl]methanone Chemical compound S1C(C)=CC=C1C1C(C(=O)N2CCC(CNC=3N=CC(C)=CN=3)CC2)C1 DQBNHVGZLDSTOB-UHFFFAOYSA-N 0.000 description 1
- YTBWKCZNTNGVFO-XZOQPEGZSA-N [4-[[[5-(2-cyclopropylethynyl)pyrimidin-2-yl]amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound C1([C@@H]2C[C@H]2C(=O)N2CCC(CNC=3N=CC(=CN=3)C#CC3CC3)CC2)=CC=CC=C1 YTBWKCZNTNGVFO-XZOQPEGZSA-N 0.000 description 1
- KPPAZGWKNIALBJ-ZWKOTPCHSA-N [4-fluoro-4-[[(5-methylpyrimidin-2-yl)amino]methyl]piperidin-1-yl]-[(1r,2r)-2-phenylcyclopropyl]methanone Chemical compound N1=CC(C)=CN=C1NCC1(F)CCN(C(=O)[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 KPPAZGWKNIALBJ-ZWKOTPCHSA-N 0.000 description 1
- YZOPDLOWTAWGNF-UHFFFAOYSA-N [Cu]C#N.[N] Chemical compound [Cu]C#N.[N] YZOPDLOWTAWGNF-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 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
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229950011175 aminopicoline Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000008359 benzonitriles Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- GYSTVZNTRDGINE-CHWSQXEVSA-N benzyl (3s,4r)-3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound C1[C@@H](O)[C@@H](CO)CCN1C(=O)OCC1=CC=CC=C1 GYSTVZNTRDGINE-CHWSQXEVSA-N 0.000 description 1
- MMGCRLHCGDSTGW-UYAOXDASSA-N benzyl (3s,4r)-3-hydroxy-4-[(4-methylphenyl)sulfonyloxymethyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1[C@H](O)CN(C(=O)OCC=2C=CC=CC=2)CC1 MMGCRLHCGDSTGW-UYAOXDASSA-N 0.000 description 1
- UTZLYIFQYGQUPA-UHFFFAOYSA-N benzyl 2,5-dioxopyrrolidine-1-carboxylate Chemical compound O=C1CCC(=O)N1C(=O)OCC1=CC=CC=C1 UTZLYIFQYGQUPA-UHFFFAOYSA-N 0.000 description 1
- XZSJRIXYFJGYLI-UHFFFAOYSA-N benzyl 3-[(7h-purin-6-ylamino)methyl]pyrrolidine-1-carboxylate Chemical compound C1CC(CNC=2C=3N=CNC=3N=CN=2)CN1C(=O)OCC1=CC=CC=C1 XZSJRIXYFJGYLI-UHFFFAOYSA-N 0.000 description 1
- XGMKVNLEZLCBGE-UHFFFAOYSA-N benzyl 3-[(pteridin-4-ylamino)methyl]pyrrolidine-1-carboxylate Chemical compound C1CC(CNC=2C3=NC=CN=C3N=CN=2)CN1C(=O)OCC1=CC=CC=C1 XGMKVNLEZLCBGE-UHFFFAOYSA-N 0.000 description 1
- RYDOCGPSSFKGRY-UHFFFAOYSA-N benzyl 4-[(1,2-oxazol-3-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC2=NOC=C2)CCN1C(=O)OCC1=CC=CC=C1 RYDOCGPSSFKGRY-UHFFFAOYSA-N 0.000 description 1
- JRLRJUXCVXQXRI-UHFFFAOYSA-N benzyl 4-[(1,3,4-thiadiazol-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2SC=NN=2)CCN1C(=O)OCC1=CC=CC=C1 JRLRJUXCVXQXRI-UHFFFAOYSA-N 0.000 description 1
- WOIDDZSLDVWACJ-UHFFFAOYSA-N benzyl 4-[(1,3-thiazol-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2SC=CN=2)CCN1C(=O)OCC1=CC=CC=C1 WOIDDZSLDVWACJ-UHFFFAOYSA-N 0.000 description 1
- ICGHKMVQSPIFQO-UHFFFAOYSA-N benzyl 4-[(1h-benzimidazol-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C=3N=CNC=3C=CC=2)CCN1C(=O)OCC1=CC=CC=C1 ICGHKMVQSPIFQO-UHFFFAOYSA-N 0.000 description 1
- SSXZHYIUNBTTFG-UHFFFAOYSA-N benzyl 4-[(3-hydroxypyridin-4-yl)carbamoyl]piperidine-1-carboxylate Chemical compound OC1=CN=CC=C1NC(=O)C1CCN(C(=O)OCC=2C=CC=CC=2)CC1 SSXZHYIUNBTTFG-UHFFFAOYSA-N 0.000 description 1
- OYXBQQMNZLTQTK-UHFFFAOYSA-N benzyl 4-[(pteridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C3=NC=CN=C3N=CN=2)CCN1C(=O)OCC1=CC=CC=C1 OYXBQQMNZLTQTK-UHFFFAOYSA-N 0.000 description 1
- KDHKDFONLOHKCA-UHFFFAOYSA-N benzyl 4-[(pyrazin-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2N=CC=NC=2)CCN1C(=O)OCC1=CC=CC=C1 KDHKDFONLOHKCA-UHFFFAOYSA-N 0.000 description 1
- HCPTWYLIFOSQGR-UHFFFAOYSA-N benzyl 4-[(pyridazin-3-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2N=NC=CC=2)CCN1C(=O)OCC1=CC=CC=C1 HCPTWYLIFOSQGR-UHFFFAOYSA-N 0.000 description 1
- BKWXCVZIALOBBS-UHFFFAOYSA-N benzyl 4-[(pyridin-2-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2N=CC=CC=2)CCN1C(=O)OCC1=CC=CC=C1 BKWXCVZIALOBBS-UHFFFAOYSA-N 0.000 description 1
- FMAJVYNCYIOPMK-UHFFFAOYSA-N benzyl 4-[(pyridin-3-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C=NC=CC=2)CCN1C(=O)OCC1=CC=CC=C1 FMAJVYNCYIOPMK-UHFFFAOYSA-N 0.000 description 1
- FYSGQXFZTQLFNI-UHFFFAOYSA-N benzyl 4-[(quinolin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C3=CC=CC=C3N=CC=2)CCN1C(=O)OCC1=CC=CC=C1 FYSGQXFZTQLFNI-UHFFFAOYSA-N 0.000 description 1
- HGOKQSXFQNKOAI-UHFFFAOYSA-N benzyl 4-[[(2-amino-7h-purin-6-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C=12N=CNC2=NC(N)=NC=1NCC(CC1)CCN1C(=O)OCC1=CC=CC=C1 HGOKQSXFQNKOAI-UHFFFAOYSA-N 0.000 description 1
- BCCKKHXEMCBNJY-UHFFFAOYSA-N benzyl 4-[[(2-chloropyridin-3-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=NC=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 BCCKKHXEMCBNJY-UHFFFAOYSA-N 0.000 description 1
- DOOICQGYCNYLSS-UHFFFAOYSA-N benzyl 4-[[(3-chloropyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=CC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 DOOICQGYCNYLSS-UHFFFAOYSA-N 0.000 description 1
- XUAXNZSJIQNTCG-UHFFFAOYSA-N benzyl 4-[[(3-cyanopyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C(=CC=CN=2)C#N)CCN1C(=O)OCC1=CC=CC=C1 XUAXNZSJIQNTCG-UHFFFAOYSA-N 0.000 description 1
- RXRRRSCVGYGYID-UHFFFAOYSA-N benzyl 4-[[(3-ethoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CCOC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 RXRRRSCVGYGYID-UHFFFAOYSA-N 0.000 description 1
- GVRFQOUABZPMOC-UHFFFAOYSA-N benzyl 4-[[(3-methoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 GVRFQOUABZPMOC-UHFFFAOYSA-N 0.000 description 1
- JBSXENDNOIGSLB-UHFFFAOYSA-N benzyl 4-[[(3-methylpyridin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CN=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 JBSXENDNOIGSLB-UHFFFAOYSA-N 0.000 description 1
- GBTMQFREUGOZKL-UHFFFAOYSA-N benzyl 4-[[(3-propan-2-yloxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC(C)OC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 GBTMQFREUGOZKL-UHFFFAOYSA-N 0.000 description 1
- FLCXVYJWSPZMIJ-UHFFFAOYSA-N benzyl 4-[[(4-ethylpyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CCC1=CC=NC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 FLCXVYJWSPZMIJ-UHFFFAOYSA-N 0.000 description 1
- SZZBJJQYIQYKOS-UHFFFAOYSA-N benzyl 4-[[(4-methylpyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound CC1=CC=NC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 SZZBJJQYIQYKOS-UHFFFAOYSA-N 0.000 description 1
- TVBZIAXALCENBB-UHFFFAOYSA-N benzyl 4-[[(5-chloropyridazin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound ClC1=CN=NC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 TVBZIAXALCENBB-UHFFFAOYSA-N 0.000 description 1
- QYQHUUUTMCZIBA-UHFFFAOYSA-N benzyl 4-[[(5-chloropyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate;hydrochloride Chemical compound Cl.ClC1=CN=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 QYQHUUUTMCZIBA-UHFFFAOYSA-N 0.000 description 1
- QXTXXZQBKVXIIE-UHFFFAOYSA-N benzyl 4-[[(5-fluoropyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound FC1=CN=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 QXTXXZQBKVXIIE-UHFFFAOYSA-N 0.000 description 1
- DRWHTJOAMXFKDQ-UHFFFAOYSA-N benzyl 4-[[(5-methylpyridin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=CC(C)=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 DRWHTJOAMXFKDQ-UHFFFAOYSA-N 0.000 description 1
- YJNDIOLFQZMXFZ-UHFFFAOYSA-N benzyl 4-[[(6-chloropyridazin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=NC(Cl)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 YJNDIOLFQZMXFZ-UHFFFAOYSA-N 0.000 description 1
- GZKXMCKRPFLPIS-UHFFFAOYSA-N benzyl 4-[[(6-chloropyrimidin-4-yl)amino]methyl]piperidine-1-carboxylate Chemical compound C1=NC(Cl)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 GZKXMCKRPFLPIS-UHFFFAOYSA-N 0.000 description 1
- QQOVFKUSEPUDET-UHFFFAOYSA-N benzyl 4-[[(6-oxo-1h-pyridazin-3-yl)amino]methyl]piperidine-1-carboxylate Chemical compound N1=NC(O)=CC=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 QQOVFKUSEPUDET-UHFFFAOYSA-N 0.000 description 1
- XILVEDFKMAPMFA-UHFFFAOYSA-N benzyl 4-[[[2-(methylaminomethyl)pyridin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1=NC(CNC)=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=C1 XILVEDFKMAPMFA-UHFFFAOYSA-N 0.000 description 1
- UEJKPKFMLUTSED-UHFFFAOYSA-N benzyl 4-[[[3-(aminomethyl)pyrazin-2-yl]amino]methyl]piperidine-1-carboxylate Chemical compound NCC1=NC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 UEJKPKFMLUTSED-UHFFFAOYSA-N 0.000 description 1
- XGOGFFHVSAHVRQ-UHFFFAOYSA-N benzyl 4-[[[3-(trifluoromethyl)pyridin-2-yl]amino]methyl]piperidine-1-carboxylate Chemical compound FC(F)(F)C1=CC=CN=C1NCC1CCN(C(=O)OCC=2C=CC=CC=2)CC1 XGOGFFHVSAHVRQ-UHFFFAOYSA-N 0.000 description 1
- DAHPFXSRBIMPDN-UHFFFAOYSA-N benzyl 4-[[[6-(aminomethyl)pyrazin-2-yl]amino]methyl]piperidine-1-carboxylate Chemical compound NCC1=CN=CC(NCC2CCN(CC2)C(=O)OCC=2C=CC=CC=2)=N1 DAHPFXSRBIMPDN-UHFFFAOYSA-N 0.000 description 1
- XVSOLNIURSFPEU-UHFFFAOYSA-N benzyl 4-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate Chemical compound C1CC(C(=O)N(C)OC)CCN1C(=O)OCC1=CC=CC=C1 XVSOLNIURSFPEU-UHFFFAOYSA-N 0.000 description 1
- BZHPVEHRXAKHMV-UHFFFAOYSA-N benzyl n-(piperidin-4-ylmethyl)carbamate Chemical compound C=1C=CC=CC=1COC(=O)NCC1CCNCC1 BZHPVEHRXAKHMV-UHFFFAOYSA-N 0.000 description 1
- TUWZZXGAUMSUOB-UHFFFAOYSA-N benzyl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OCC1=CC=CC=C1 TUWZZXGAUMSUOB-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- MZJUGRUTVANEDW-UHFFFAOYSA-N bromine fluoride Chemical compound BrF MZJUGRUTVANEDW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 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
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical class OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- BLEBFDYUDVZRFG-UHFFFAOYSA-N dichloromethane;propan-2-ol Chemical compound ClCCl.CC(C)O BLEBFDYUDVZRFG-UHFFFAOYSA-N 0.000 description 1
- ZBQUMMFUJLOTQC-UHFFFAOYSA-L dichloronickel;3-diphenylphosphanylpropyl(diphenyl)phosphane Chemical compound Cl[Ni]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 ZBQUMMFUJLOTQC-UHFFFAOYSA-L 0.000 description 1
- 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 1
- AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 1
- SLIKWVTWIGHFJE-UHFFFAOYSA-N diphenoxymethylidenecyanamide Chemical compound C=1C=CC=CC=1OC(=NC#N)OC1=CC=CC=C1 SLIKWVTWIGHFJE-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010410 dusting Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- UQOMEAWPKSISII-UHFFFAOYSA-N ethyl 1-benzyl-3-oxopiperidine-4-carboxylate;hydron;chloride Chemical compound Cl.C1C(=O)C(C(=O)OCC)CCN1CC1=CC=CC=C1 UQOMEAWPKSISII-UHFFFAOYSA-N 0.000 description 1
- YCBJOQUNPLTBGG-UHFFFAOYSA-N ethyl 4-iodobenzoate Chemical compound CCOC(=O)C1=CC=C(I)C=C1 YCBJOQUNPLTBGG-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- NPTDXPDGUHAFKC-UHFFFAOYSA-N ethynylcyclopropane Chemical compound C#CC1CC1 NPTDXPDGUHAFKC-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000928 excitatory amino acid agonist Substances 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000002431 glycine receptor agonist Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 108091008634 hepatocyte nuclear factors 4 Proteins 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 102000053931 human NR1A Human genes 0.000 description 1
- 108700015659 human NR1A Proteins 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical group O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000014666 liquid concentrate Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- XETFBTXVGCQYBD-UHFFFAOYSA-N methanamine;2,2,2-trifluoroacetic acid Chemical compound [NH3+]C.[O-]C(=O)C(F)(F)F XETFBTXVGCQYBD-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- HEGMSNMENPDWJB-VOTSOKGWSA-N methyl (e)-3-(2-fluorophenyl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=CC=C1F HEGMSNMENPDWJB-VOTSOKGWSA-N 0.000 description 1
- GDWFCUOFVSNTTG-UHFFFAOYSA-N methyl 1-benzylpyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1CC1=CC=CC=C1 GDWFCUOFVSNTTG-UHFFFAOYSA-N 0.000 description 1
- CMITUAXQMWSHLL-UHFFFAOYSA-N methyl 3-bromopyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=CN=C1Br CMITUAXQMWSHLL-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- RYUCGGGAQDYSMJ-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)pyrimidin-2-amine Chemical compound C1CNCCC1CNC1=NC=CC=N1 RYUCGGGAQDYSMJ-UHFFFAOYSA-N 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
- SJTZOKQCZRRGSC-UHFFFAOYSA-N n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]-7h-purin-2-amine Chemical compound C1CC(CNC=2N=C3NC=NC3=CN=2)CCN1S(=O)(=O)CCC1=CC=CC=C1 SJTZOKQCZRRGSC-UHFFFAOYSA-N 0.000 description 1
- YBEHAAJXXATNNM-UHFFFAOYSA-N n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrazin-2-amine Chemical compound C1CC(CNC=2N=CC=NC=2)CCN1S(=O)(=O)CCC1=CC=CC=C1 YBEHAAJXXATNNM-UHFFFAOYSA-N 0.000 description 1
- XPRQIGGATQMDAQ-UHFFFAOYSA-N n-[[1-(2-phenylethylsulfonyl)piperidin-4-yl]methyl]pyrimidin-4-amine Chemical compound C1CC(CNC=2N=CN=CC=2)CCN1S(=O)(=O)CCC1=CC=CC=C1 XPRQIGGATQMDAQ-UHFFFAOYSA-N 0.000 description 1
- VSVAIXQIXZPYSX-UHFFFAOYSA-N n-[[1-[2-(2-fluorophenyl)ethylsulfonyl]piperidin-4-yl]methyl]pyrimidin-2-amine Chemical compound FC1=CC=CC=C1CCS(=O)(=O)N1CCC(CNC=2N=CC=CN=2)CC1 VSVAIXQIXZPYSX-UHFFFAOYSA-N 0.000 description 1
- LQIKZEOYOWUPJQ-UHFFFAOYSA-N n-[[1-[2-(4-chlorophenyl)ethylsulfonyl]piperidin-4-yl]methyl]pyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1CCS(=O)(=O)N1CCC(CNC=2N=CC=CN=2)CC1 LQIKZEOYOWUPJQ-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- GTUJJVSZIHQLHA-XPWFQUROSA-N pApA Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@@H]1O)O[C@H](COP(O)(O)=O)[C@H]1OP(O)(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=CN=C2N)=C2N=C1 GTUJJVSZIHQLHA-XPWFQUROSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 235000014483 powder concentrate Nutrition 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
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- UYLWKSJTHLRFBX-UHFFFAOYSA-N purin-6-one Chemical class O=C1N=CN=C2N=CN=C12 UYLWKSJTHLRFBX-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- RNORHZTZTKRDFU-UHFFFAOYSA-N s-[2-(4-fluorophenyl)ethyl] ethanethioate Chemical compound CC(=O)SCCC1=CC=C(F)C=C1 RNORHZTZTKRDFU-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- SZFYKONCRGEAKI-WDEREUQCSA-N tert-butyl (1r,2r)-2-(2-fluorophenyl)cyclopropane-1-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1C[C@H]1C1=CC=CC=C1F SZFYKONCRGEAKI-WDEREUQCSA-N 0.000 description 1
- ULSBMKGFFFMGOI-UHFFFAOYSA-N tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11OC1 ULSBMKGFFFMGOI-UHFFFAOYSA-N 0.000 description 1
- NFEGNISFSSLEGU-UHFFFAOYSA-N tert-butyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC(C)(C)C NFEGNISFSSLEGU-UHFFFAOYSA-N 0.000 description 1
- WSESXRUBHUASPJ-UHFFFAOYSA-N tert-butyl 4-[[(5-cyano-3-methoxypyrazin-2-yl)amino]methyl]piperidine-1-carboxylate Chemical compound COC1=NC(C#N)=CN=C1NCC1CCN(C(=O)OC(C)(C)C)CC1 WSESXRUBHUASPJ-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- JDDPITNKUXPLSB-UHFFFAOYSA-N tert-butyl morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOCC1 JDDPITNKUXPLSB-UHFFFAOYSA-N 0.000 description 1
- RHADKSJLBACINV-UHFFFAOYSA-N tert-butyl n-[[1-(2-phenylcyclopropanecarbonyl)piperidin-4-yl]methyl]carbamate Chemical compound C1CC(CNC(=O)OC(C)(C)C)CCN1C(=O)C1C(C=2C=CC=CC=2)C1 RHADKSJLBACINV-UHFFFAOYSA-N 0.000 description 1
- RHADKSJLBACINV-ZWKOTPCHSA-N tert-butyl n-[[1-[(1r,2r)-2-phenylcyclopropanecarbonyl]piperidin-4-yl]methyl]carbamate Chemical compound C1CC(CNC(=O)OC(C)(C)C)CCN1C(=O)[C@H]1[C@H](C=2C=CC=CC=2)C1 RHADKSJLBACINV-ZWKOTPCHSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 108091008646 testicular receptors Proteins 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- XMLLKMGPNFMXEA-UHFFFAOYSA-N thiophen-3-ylmethyl 4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate Chemical compound C1CC(CNC=2C=CN=CC=2)CCN1C(=O)OCC=1C=CSC=1 XMLLKMGPNFMXEA-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000000260 trans-2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])[C@]1([H])C([H])([H])[C@@]1([H])* 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
- C07D475/08—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US27110001P | 2001-02-23 | 2001-02-23 | |
PCT/US2002/005226 WO2002068409A1 (en) | 2001-02-23 | 2002-02-20 | N-substituted nonaryl-heterocyclic nmda/nr2b antagonists |
Publications (1)
Publication Number | Publication Date |
---|---|
SK10542003A3 true SK10542003A3 (sk) | 2004-03-02 |
Family
ID=23034191
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1054-2003A SK10542003A3 (sk) | 2001-02-23 | 2002-02-20 | N-Substituované nearylové heterocyklické zlúčeniny, farmaceutický prostriedok s ich obsahom a ich použitie |
Country Status (33)
Country | Link |
---|---|
US (2) | US7217716B2 (pt) |
EP (1) | EP1379520B2 (pt) |
JP (1) | JP4179879B2 (pt) |
KR (1) | KR100849839B1 (pt) |
CN (1) | CN100567293C (pt) |
AT (1) | ATE324371T1 (pt) |
AU (1) | AU2002252053B2 (pt) |
BG (1) | BG108113A (pt) |
BR (1) | BR0207526A (pt) |
CA (1) | CA2438895A1 (pt) |
CZ (1) | CZ20032258A3 (pt) |
DE (1) | DE60210944T3 (pt) |
DK (1) | DK1379520T3 (pt) |
EA (1) | EA005974B1 (pt) |
EC (1) | ECSP034744A (pt) |
EE (1) | EE200300403A (pt) |
ES (1) | ES2261658T3 (pt) |
GE (1) | GEP20063741B (pt) |
HR (1) | HRP20030669A2 (pt) |
HU (1) | HUP0303258A3 (pt) |
IL (2) | IL157254A0 (pt) |
IS (1) | IS6902A (pt) |
MX (1) | MXPA03007621A (pt) |
NO (1) | NO20033732L (pt) |
NZ (1) | NZ527365A (pt) |
PL (1) | PL364625A1 (pt) |
PT (1) | PT1379520E (pt) |
SI (1) | SI1379520T1 (pt) |
SK (1) | SK10542003A3 (pt) |
UA (1) | UA75392C2 (pt) |
WO (1) | WO2002068409A1 (pt) |
YU (1) | YU64303A (pt) |
ZA (1) | ZA200306159B (pt) |
Families Citing this family (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002100352A2 (en) * | 2001-06-12 | 2002-12-19 | Merck & Co., Inc. | Nr2b receptor antagonists for the treatment or prevention of migraines |
US7163952B2 (en) * | 2001-12-03 | 2007-01-16 | Japan Tobacco Inc. | Azole compound and medicinal use thereof |
TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
ATE366045T1 (de) * | 2002-03-15 | 2007-07-15 | Ciba Sc Holding Ag | Verwendung von 4-aminopyrimidinen zur antimikrobiellen behandlung von oberflächen |
US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
AU2003231359B2 (en) | 2002-04-16 | 2009-04-30 | Teijin Limited | Piperidine derivatives having CCR3 antagonism |
KR20040104596A (ko) | 2002-04-25 | 2004-12-10 | 데이진 가부시키가이샤 | Ccr3 길항 작용을 갖는 4,4-2치환 피페리딘 유도체 |
MXPA05001096A (es) | 2002-07-29 | 2005-11-23 | Rigel Pharmaceuticals Inc | Metodos para tratamiento o prevencion de enfermedades autoinmunes con compuestos de 2,4-diamino-pirimidina. |
JP2004315511A (ja) * | 2003-03-31 | 2004-11-11 | Taisho Pharmaceut Co Ltd | Mch受容体アンタゴニスト |
UA81319C2 (en) * | 2003-06-04 | 2007-12-25 | Merck & Co Inc | 3-fluoro-piperidines as nmda/nr2b antagonists |
US7592360B2 (en) | 2003-06-04 | 2009-09-22 | Merck & Co., Inc. | 3-fluoro-piperidines as NMDA/NR2B antagonists |
CA2533377C (en) | 2003-07-30 | 2012-11-27 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
MXPA06002964A (es) | 2003-09-16 | 2006-06-14 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de cinasa de tirosina. |
GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
WO2005075439A1 (en) | 2004-02-03 | 2005-08-18 | Astrazeneca Ab | Quinazoline derivatives |
RU2006139258A (ru) | 2004-04-08 | 2008-05-20 | Таргеджен, Инк. (US) | Бензотриазиновые ингибиторы киназ |
CA2575430A1 (en) * | 2004-08-03 | 2006-02-16 | Merck & Co., Inc. | 1,3-disubstituted heteroaryl nmda/nr2b antagonists |
US20080153917A1 (en) * | 2004-09-10 | 2008-06-26 | Ucb Pharma, S.A. | Sigma Receptor Ligands |
US7776869B2 (en) | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
CA2584295C (en) | 2004-11-24 | 2014-08-26 | Rigel Pharmaceuticals, Inc. | Spiro-2, 4-pyrimidinediamine compounds and their uses |
CA2613235A1 (en) | 2005-06-30 | 2007-01-11 | Prosidion Limited | Gpcr agonists |
JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
BR122021011787B1 (pt) | 2005-11-01 | 2022-01-25 | Impact Biomedicines, Inc | Inibidores de biaril meta pirimidina de cinases, composição farmacêutica e processo para preparar uma composição farmacêutica |
CN101346368A (zh) * | 2005-12-21 | 2009-01-14 | 詹森药业有限公司 | 作为α2C-肾上腺素受体拮抗剂的取代的吡嗪酮衍生物 |
US7935706B2 (en) | 2006-02-23 | 2011-05-03 | Shionogi & Co., Ltd. | Nitrogen-containing heterocycle derivatives substituted with cyclic group |
BRPI0709699A2 (pt) * | 2006-03-29 | 2011-07-26 | Foldrx Pharmaceuticals Inc | inibiÇço da toxidez da alfa-sinucleina |
EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
JP5179509B2 (ja) * | 2006-12-08 | 2013-04-10 | エフ.ホフマン−ラ ロシュ アーゲー | 置換ピリミジン類及びjnkモジュレーターとしてのこれらの使用 |
JO2642B1 (en) | 2006-12-08 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
US7998949B2 (en) | 2007-02-06 | 2011-08-16 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof |
JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
DK2148873T3 (da) * | 2007-04-23 | 2012-11-26 | Janssen Pharmaceutica Nv | 4-alkoxypyridazinderivater som hurtigt dissocierende dopamin 2- receptorantagonister |
CA2682671C (en) | 2007-04-23 | 2015-11-17 | Janssen Pharmaceutica N.V. | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
CN101835750B (zh) * | 2007-08-22 | 2013-07-17 | 阿斯利康(瑞典)有限公司 | 环丙基酰胺衍生物 |
US20100249164A1 (en) * | 2007-10-31 | 2010-09-30 | Renger John J | Modulation of sleep with nr2b receptor antagonists |
MY150290A (en) | 2008-02-07 | 2013-12-31 | Boehringer Ingelheim Int | Spirocyclic heterocycles, medicaments containing said compounds, use thereof and method for their production |
US8088782B2 (en) | 2008-05-13 | 2012-01-03 | Astrazeneca Ab | Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A |
US8530474B2 (en) | 2008-07-03 | 2013-09-10 | Janssen Pharmaceutica Nv | Substituted 6-(1-piperazinyl)-pyridazines as 5-HT6 receptor antagonists |
US8895562B2 (en) | 2008-07-31 | 2014-11-25 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
JP5539351B2 (ja) | 2008-08-08 | 2014-07-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | シクロヘキシルオキシ置換ヘテロ環、これらの化合物を含有する医薬、およびそれらを生成するための方法 |
TW201039825A (en) * | 2009-02-20 | 2010-11-16 | Astrazeneca Ab | Cyclopropyl amide derivatives 983 |
US8389536B2 (en) | 2009-10-27 | 2013-03-05 | Hoffmann-La Roche Inc. | Positive allosteric modulators (PAM) |
BR112012020782A2 (pt) * | 2010-02-18 | 2016-05-03 | Astrazeneca Ab | composto, e, processo para preparar um composto |
TW201136898A (en) * | 2010-02-18 | 2011-11-01 | Astrazeneca Ab | Solid forms comprising a cyclopropyl amide derivative |
AU2010363329A1 (en) | 2010-11-07 | 2013-05-09 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
JP6001049B2 (ja) * | 2011-03-31 | 2016-10-05 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングBayer Intellectual Property GmbH | Mps−1キナーゼ阻害剤としての置換ベンズイミダゾール類 |
US8722670B2 (en) * | 2011-09-30 | 2014-05-13 | Bristol-Myers Squibb Company | Selective NR2B antagonists |
CN104321057B (zh) | 2012-04-20 | 2016-09-14 | Ucb医药有限公司 | 用于治疗帕金森病的方法 |
JP2016028017A (ja) * | 2012-12-13 | 2016-02-25 | 大正製薬株式会社 | フッ素置換ピペリジン化合物 |
JP2017001954A (ja) * | 2013-11-08 | 2017-01-05 | 石原産業株式会社 | 含窒素飽和複素環化合物 |
WO2015182724A1 (ja) * | 2014-05-28 | 2015-12-03 | トーアエイヨー株式会社 | 置換トロパン誘導体 |
AU2015271719A1 (en) * | 2014-06-04 | 2016-12-01 | Rugen Holdings (Cayman) Limited | Difluoroethylpyridine derivatives as NR2B NMDA receptor antagonists |
AU2015317886A1 (en) * | 2014-09-15 | 2017-03-09 | Rugen Holdings (Cayman) Limited | Pyrrolopyrimidine derivatives as NR2B NMDA receptor antagonists |
WO2016100349A2 (en) * | 2014-12-16 | 2016-06-23 | Rugen Holdings (Cayman) Limited | Bicyclic azaheterocyclic compounds as nr2b nmda receptor antagonists |
EP3253761A4 (en) | 2015-02-04 | 2018-06-20 | Rugen Holdings (Cayman) Limited | 3,3-difluoro-piperidine derivatives as nr2b nmda receptor antagonists |
US10584102B2 (en) | 2015-05-11 | 2020-03-10 | Basf Se | Process for preparing 4-amino-pyridazines |
EP3303323B1 (en) | 2015-06-01 | 2020-01-08 | Rugen Holdings (Cayman) Limited | 3,3-difluoropiperidine carbamate heterocyclic compounds as nr2b nmda receptor antagonists |
WO2018098128A1 (en) | 2016-11-22 | 2018-05-31 | Rugen Holdings (Cayman) Limited | Treatment of autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders |
CA3097740A1 (en) * | 2018-02-23 | 2019-08-29 | Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. | Novel inhibitors of bacterial glutaminyl cyclases for use in the treatment of periodontal and related diseases |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL265777A (pt) * | 1960-06-09 | |||
DE2341965C3 (de) * | 1973-08-20 | 1979-01-25 | C.H. Boehringer Sohn, 6507 Ingelheim | 4- [N- (o-PyridyD- N-acyl] -aminolphenäthylpiperidine, Verfahren zu deren Herstellung sowie deren Verwendung bei der Bekämpfung von Schmerzzuständen |
US4197304A (en) | 1975-09-23 | 1980-04-08 | Janssen Pharmaceutica N.V. | N-Aryl-N-(1-L-4-piperidinyl)-arylacetamides |
EP0126087A1 (en) * | 1982-09-24 | 1984-11-28 | Beecham Group Plc | Amino-azabicycloalkyl derivatives as dopamine antagonists |
RU2099339C1 (ru) | 1990-02-06 | 1997-12-20 | Пфайзер Инк. | Производные пиперидина |
DK0554247T3 (da) | 1990-05-10 | 2000-08-07 | Pfizer | Neurobeskyttende indolon og beslægtede derivater |
US5189036A (en) | 1990-06-20 | 1993-02-23 | Schering Ag | Imidazolylbenzoyl substituted heterocycles |
EP0584192A1 (en) | 1991-04-18 | 1994-03-02 | Pfizer Inc. | Prodrug esters of phenolic 2-piperidino-1-alkanols |
WO1993002052A1 (en) | 1991-07-17 | 1993-02-04 | Pfizer Inc. | 2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents |
MY110227A (en) | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
SI9300097B (en) * | 1992-02-27 | 2001-12-31 | Janssen Pharmaceutica Nv | (benzodioxan, benzofuran or benzopyran) alkylamino) alkyl substituted guanidines |
DK55192D0 (da) * | 1992-04-28 | 1992-04-28 | Lundbeck & Co As H | 1-piperazino-1,2-dihydroindenderivater |
US5436255A (en) | 1992-07-23 | 1995-07-25 | Pfizer Inc. | Method of treating diseases susceptable to treatment by blocking NMDA-receptors |
DE4241632A1 (de) | 1992-12-10 | 1994-06-16 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
WO1994014776A2 (en) | 1992-12-21 | 1994-07-07 | Smithkline Beecham Corporation | Bicyclic fibrinogen antagonists |
DE4304650A1 (de) | 1993-02-16 | 1994-08-18 | Thomae Gmbh Dr K | Kondensierte 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
AU6252794A (en) | 1993-03-03 | 1994-09-26 | Eli Lilly And Company | Balanoids |
JPH08508030A (ja) | 1993-03-18 | 1996-08-27 | メルク シヤープ エンド ドーム リミテツド | ベンゾイミダゾール誘導体 |
AU3138595A (en) | 1994-07-20 | 1996-02-16 | Acea Pharmaceuticals, Inc. | Haloperidol analogs and the use thereof |
US5661161A (en) | 1994-09-29 | 1997-08-26 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
EP0742208A1 (en) | 1995-05-05 | 1996-11-13 | Grelan Pharmaceutical Co., Ltd. | 2-Ureido-benzamide derivatives |
MX9709112A (es) | 1995-05-26 | 1998-02-28 | Pfizer | Combinacion para el tratamiento de parkinsonismo que contienen antagonistas selectivos de n-metil-d-aspartato. |
DE19541264A1 (de) | 1995-11-06 | 1997-05-07 | Bayer Ag | Purin-6-on-derivate |
EP0771779B1 (en) | 1995-11-06 | 2002-05-02 | Kuraray Co., Ltd. | Process for producing acetals |
GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
ZA9610745B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
FR2744449B1 (fr) | 1996-02-02 | 1998-04-24 | Pf Medicament | Nouvelles piperazines aromatiques derivees de cycloazanes substitues, ainsi que leur procede de preparation, les compositions pharmaceutiques et leur utilisation comme medicaments |
EP0787493A1 (en) | 1996-02-03 | 1997-08-06 | F. Hoffmann-La Roche Ag | Tetrahydroisoquinoline derivatives |
TW504510B (en) * | 1996-05-10 | 2002-10-01 | Janssen Pharmaceutica Nv | 2,4-diaminopyrimidine derivatives |
AU2898297A (en) | 1996-05-24 | 1998-01-05 | Novartis Ag | Use of substance p antagonists for treating social phobia |
ES2271971T3 (es) | 1996-07-25 | 2007-04-16 | Biogen Idec Ma Inc. | Inhibidores de la adhesion celular. |
DZ2285A1 (fr) | 1996-08-08 | 2002-12-25 | Smithkline Beecham Corp | Inhibiteurs de protéase de la cystéine. |
EP0846683B1 (en) | 1996-12-03 | 2001-09-19 | F. Hoffmann-La Roche Ag | 4-Hydroxy-piperidine derivatives |
FR2758327B1 (fr) | 1997-01-15 | 1999-04-02 | Pf Medicament | Nouvelles arylpiperazines derivees de piperidine |
FR2758328B1 (fr) | 1997-01-15 | 1999-04-02 | Pf Medicament | Nouvelles amines aromatiques derivees d'amines cycliques utiles comme medicaments |
IT1291569B1 (it) | 1997-04-15 | 1999-01-11 | Angelini Ricerche Spa | Indazolammidi come agenti serotoninergici |
US6020347A (en) | 1997-11-18 | 2000-02-01 | Merck & Co., Inc. | 4-substituted-4-piperidine carboxamide derivatives |
AU1415099A (en) | 1997-11-18 | 1999-06-07 | Merck & Co., Inc. | 4-substituted-4-piperidine carboxamide derivatives |
DE19815026A1 (de) * | 1998-04-03 | 1999-10-07 | Hoechst Schering Agrevo Gmbh | Substituierte Piperidine, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und Fungizide |
PE20000728A1 (es) | 1998-06-26 | 2000-08-21 | Cocensys Inc | Heterociclos 4-bencil piperidina alquilsulfoxido y su uso como antagonistas receptores subtipo-selectivo nmda |
ES2261844T3 (es) | 1998-08-07 | 2006-11-16 | Applied Research Systems Ars Holding N.V. | Mimeticos de la fsh para el tratamiento de la infertilidad. |
DE19838300A1 (de) | 1998-08-24 | 2000-03-02 | Bayer Ag | 9-Dialkylaminopurinon-derivate |
US6303637B1 (en) | 1998-10-30 | 2001-10-16 | Merck & Co., Inc. | Heterocyclic potassium channel inhibitors |
JP3936844B2 (ja) | 1999-04-13 | 2007-06-27 | ビーエーエスエフ アクチェンゲゼルシャフト | インテグリンレセプターリガンド |
AU6605200A (en) | 1999-06-30 | 2001-01-31 | Merck & Co., Inc. | Src kinase inhibitor compounds |
-
2002
- 2002-02-20 US US10/470,561 patent/US7217716B2/en not_active Expired - Fee Related
- 2002-02-20 BR BR0207526-1A patent/BR0207526A/pt not_active IP Right Cessation
- 2002-02-20 WO PCT/US2002/005226 patent/WO2002068409A1/en active IP Right Grant
- 2002-02-20 US US10/079,452 patent/US7053089B2/en not_active Expired - Lifetime
- 2002-02-20 AU AU2002252053A patent/AU2002252053B2/en not_active Ceased
- 2002-02-20 EA EA200300919A patent/EA005974B1/ru not_active IP Right Cessation
- 2002-02-20 SK SK1054-2003A patent/SK10542003A3/sk not_active Application Discontinuation
- 2002-02-20 KR KR1020037011079A patent/KR100849839B1/ko not_active IP Right Cessation
- 2002-02-20 GE GE5284A patent/GEP20063741B/en unknown
- 2002-02-20 YU YU64303A patent/YU64303A/sh unknown
- 2002-02-20 DE DE60210944.2T patent/DE60210944T3/de not_active Expired - Lifetime
- 2002-02-20 IL IL15725402A patent/IL157254A0/xx active IP Right Grant
- 2002-02-20 PL PL02364625A patent/PL364625A1/xx not_active Application Discontinuation
- 2002-02-20 CZ CZ20032258A patent/CZ20032258A3/cs unknown
- 2002-02-20 PT PT02721105T patent/PT1379520E/pt unknown
- 2002-02-20 ES ES02721105T patent/ES2261658T3/es not_active Expired - Lifetime
- 2002-02-20 DK DK02721105T patent/DK1379520T3/da active
- 2002-02-20 EP EP02721105.1A patent/EP1379520B2/en not_active Expired - Lifetime
- 2002-02-20 SI SI200230322T patent/SI1379520T1/sl unknown
- 2002-02-20 CN CNB028087135A patent/CN100567293C/zh not_active Expired - Fee Related
- 2002-02-20 HU HU0303258A patent/HUP0303258A3/hu unknown
- 2002-02-20 UA UA2003098659A patent/UA75392C2/uk unknown
- 2002-02-20 NZ NZ527365A patent/NZ527365A/en unknown
- 2002-02-20 CA CA002438895A patent/CA2438895A1/en not_active Abandoned
- 2002-02-20 EE EEP200300403A patent/EE200300403A/xx unknown
- 2002-02-20 JP JP2002567923A patent/JP4179879B2/ja not_active Expired - Fee Related
- 2002-02-20 AT AT02721105T patent/ATE324371T1/de not_active IP Right Cessation
- 2002-02-20 MX MXPA03007621A patent/MXPA03007621A/es active IP Right Grant
-
2003
- 2003-07-31 IS IS6902A patent/IS6902A/is unknown
- 2003-08-05 IL IL157254A patent/IL157254A/en not_active IP Right Cessation
- 2003-08-08 ZA ZA200306159A patent/ZA200306159B/en unknown
- 2003-08-19 BG BG108113A patent/BG108113A/bg unknown
- 2003-08-22 NO NO20033732A patent/NO20033732L/no not_active Application Discontinuation
- 2003-08-22 HR HR20030669A patent/HRP20030669A2/hr not_active Application Discontinuation
- 2003-08-22 EC EC2003004744A patent/ECSP034744A/es unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4179879B2 (ja) | N−置換非アリール系複素環nmda/nr2b拮抗薬 | |
AU2002252053A1 (en) | N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists | |
US7259157B2 (en) | N-substituted nonaryl-heterocyclo amidyl NMDA/NR2B Antagonists | |
AU2006327876B2 (en) | Pyrimidine derivatives | |
AU2010313397B2 (en) | Phenoxy-substituted pyrimidines as opioid receptor modulators | |
US20040204341A1 (en) | Nr2b receptor antagonists for the treatment or prevention of migraines | |
AU2002338334A1 (en) | N-substituted nonaryl-heterocyclo amidyl NMDA/NR2B antagonists | |
CA2603876A1 (en) | N-alkyl-azacycloalkyl nmda/nr2b antagonists | |
KR101794321B1 (ko) | 바이사이클릭 그룹 치환된 피리미딘 화합물 | |
JP2002161095A (ja) | 1h−イミダゾピリジン誘導体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FC9A | Refused patent application |