SK15252003A3 - Deriváty imidazo[1,5-a]pyrimido[5,4-d][1]benzazepínu ako GABA a modulátory receptora - Google Patents
Deriváty imidazo[1,5-a]pyrimido[5,4-d][1]benzazepínu ako GABA a modulátory receptora Download PDFInfo
- Publication number
- SK15252003A3 SK15252003A3 SK1525-2003A SK15252003A SK15252003A3 SK 15252003 A3 SK15252003 A3 SK 15252003A3 SK 15252003 A SK15252003 A SK 15252003A SK 15252003 A3 SK15252003 A3 SK 15252003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- pyrimido
- benzazepine
- formula
- compound
- imidazo
- Prior art date
Links
- 102000004300 GABA-A Receptors Human genes 0.000 title description 12
- 108090000839 GABA-A Receptors Proteins 0.000 title description 12
- RZBORXKBSMHCCE-UHFFFAOYSA-N 2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),4,6,8,10,12,14,16-octaene Chemical class C=1C2=CN=CN=C2C2=CC=CC=C2N2CN=CC2=1 RZBORXKBSMHCCE-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 13
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 4
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 20
- -1 3-Cyclopropyl-1,2,4-oxadiazol-5-yl Chemical group 0.000 claims description 19
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000004494 ethyl ester group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- MWHPHTGINPRZTH-UHFFFAOYSA-N 11H-pyrimido[5,4-d][1]benzazepine-10-carboxylic acid Chemical compound N1=CN=CC2=CC=NC=3C(=C21)CC(=CC=3)C(=O)O MWHPHTGINPRZTH-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- LKSZKMYOORFVLF-UHFFFAOYSA-N C(C)OC(=O)C=1N=CN=C2C1CC=1N(C3=C2C(=CC(=C3)Br)CC)C(=NC1)C Chemical compound C(C)OC(=O)C=1N=CN=C2C1CC=1N(C3=C2C(=CC(=C3)Br)CC)C(=NC1)C LKSZKMYOORFVLF-UHFFFAOYSA-N 0.000 claims 1
- HHSAHSOSPPDOKX-UHFFFAOYSA-N N1C=NC=C2C=CN=C3C(=C21)C=CC=C3 Chemical compound N1C=NC=C2C=CN=C3C(=C21)C=CC=C3 HHSAHSOSPPDOKX-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 102000005962 receptors Human genes 0.000 abstract description 11
- 108020003175 receptors Proteins 0.000 abstract description 11
- 230000027455 binding Effects 0.000 abstract description 10
- 239000002475 cognitive enhancer Substances 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 126
- 239000007787 solid Substances 0.000 description 107
- 239000000203 mixture Substances 0.000 description 71
- 239000000243 solution Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 239000000047 product Substances 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- 235000002639 sodium chloride Nutrition 0.000 description 20
- OFVPEVBHNBLAHT-UHFFFAOYSA-N ethyl 11H-pyrimido[5,4-d][1]benzazepine-10-carboxylate Chemical compound C(C)OC(=O)C1=CC=C2C(=C3C(=CC=N2)C=NC=N3)C1 OFVPEVBHNBLAHT-UHFFFAOYSA-N 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 239000000284 extract Substances 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000007788 liquid Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 11
- 239000013078 crystal Substances 0.000 description 11
- YQOZAYAIFDRKAO-UHFFFAOYSA-N 4-(dimethylaminomethylidene)-1h-1-benzazepine-2,5-dione Chemical compound O=C1C(=CN(C)C)CC(=O)NC2=CC=CC=C21 YQOZAYAIFDRKAO-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000003039 volatile agent Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 8
- YZZFLLQDSQPMPN-UHFFFAOYSA-N 4-(dimethylaminomethylidene)-7-fluoro-1h-1-benzazepine-2,5-dione Chemical compound O=C1C(=CN(C)C)CC(=O)NC2=CC=C(F)C=C21 YZZFLLQDSQPMPN-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 7
- HEGOGQZKFXNZBM-UHFFFAOYSA-N 7-chloro-4-(dimethylaminomethylidene)-1h-1-benzazepine-2,5-dione Chemical compound O=C1C(=CN(C)C)CC(=O)NC2=CC=C(Cl)C=C21 HEGOGQZKFXNZBM-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- OCUSYBHPZIFMRI-UHFFFAOYSA-N 1-benzazepin-6-one Chemical class N1=CC=CC=C2C(=O)C=CC=C21 OCUSYBHPZIFMRI-UHFFFAOYSA-N 0.000 description 5
- LOJFRHBZDMXJPA-UHFFFAOYSA-N 2-(4-methoxyphenyl)ethanimidamide;hydrochloride Chemical compound Cl.COC1=CC=C(CC(N)=N)C=C1 LOJFRHBZDMXJPA-UHFFFAOYSA-N 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
- SFVCOZOGYYJPII-UHFFFAOYSA-N 7-bromo-4-(dimethylaminomethylidene)-1h-1-benzazepine-2,5-dione Chemical compound O=C1C(=CN(C)C)CC(=O)NC2=CC=C(Br)C=C21 SFVCOZOGYYJPII-UHFFFAOYSA-N 0.000 description 5
- TWLLPUMZVVGILS-UHFFFAOYSA-N Ethyl 2-aminobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N TWLLPUMZVVGILS-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical compound Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- VWXLCWNPSOUPPE-UHFFFAOYSA-N (1-amino-2-methylpropylidene)azanium;chloride Chemical compound Cl.CC(C)C(N)=N VWXLCWNPSOUPPE-UHFFFAOYSA-N 0.000 description 4
- AZVWIMLQRLKLHH-UHFFFAOYSA-N (5-methyl-1,2-oxazol-3-yl)methanamine Chemical compound CC1=CC(CN)=NO1 AZVWIMLQRLKLHH-UHFFFAOYSA-N 0.000 description 4
- 125000000980 1H-indol-3-ylmethyl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[*])C2=C1[H] 0.000 description 4
- VDTXDALRBZEUFV-UHFFFAOYSA-N 3,4-dihydro-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)CCC(=O)C2=CC=CC=C21 VDTXDALRBZEUFV-UHFFFAOYSA-N 0.000 description 4
- WOVRNMLCIGOKLG-UHFFFAOYSA-N 4-(dimethylaminomethylidene)-7,8-dimethyl-1h-1-benzazepine-2,5-dione Chemical compound O=C1C(=CN(C)C)CC(=O)NC2=CC(C)=C(C)C=C21 WOVRNMLCIGOKLG-UHFFFAOYSA-N 0.000 description 4
- LHFPSKACSUVFCV-UHFFFAOYSA-N 4-(dimethylaminomethylidene)-7-methyl-1h-1-benzazepine-2,5-dione Chemical compound O=C1C(=CN(C)C)CC(=O)NC2=CC=C(C)C=C21 LHFPSKACSUVFCV-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
- STYCVEYASXULRN-UHFFFAOYSA-N butanimidamide;hydrochloride Chemical compound [Cl-].CCCC(N)=[NH2+] STYCVEYASXULRN-UHFFFAOYSA-N 0.000 description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- MFUVDXOKPBAHMC-UHFFFAOYSA-N magnesium;dinitrate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MFUVDXOKPBAHMC-UHFFFAOYSA-N 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- VJCKESJFSQDYPK-UHFFFAOYSA-N 10-bromo-2-methyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(Br)C=C2C2=NC(C)=NC=C21 VJCKESJFSQDYPK-UHFFFAOYSA-N 0.000 description 3
- XFKCVVFQGHCLIP-UHFFFAOYSA-N 2-ethylbutanedioyl dichloride Chemical compound CCC(C(Cl)=O)CC(Cl)=O XFKCVVFQGHCLIP-UHFFFAOYSA-N 0.000 description 3
- RWJOVJVWIVBYKF-UHFFFAOYSA-N 3-(azidomethyl)-5-methyl-1,2-oxazole Chemical compound CC1=CC(CN=[N+]=[N-])=NO1 RWJOVJVWIVBYKF-UHFFFAOYSA-N 0.000 description 3
- ASGJFGPILHALRC-UHFFFAOYSA-N 3-(bromomethyl)-5-methyl-1,2-oxazole Chemical compound CC1=CC(CBr)=NO1 ASGJFGPILHALRC-UHFFFAOYSA-N 0.000 description 3
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000002920 convulsive effect Effects 0.000 description 3
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 3
- 239000002027 dichloromethane extract Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- WACITHSWEZJTPP-UHFFFAOYSA-N ethyl 17-fluoro-3-methyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)F)C(=NC=1)C WACITHSWEZJTPP-UHFFFAOYSA-N 0.000 description 3
- MPKHPDXNGHDQSL-UHFFFAOYSA-N ethyl 2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C=NC=1 MPKHPDXNGHDQSL-UHFFFAOYSA-N 0.000 description 3
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 3
- MQZTWBSNIOUVKB-UHFFFAOYSA-N ethyl 4-hydroxy-4-(2-nitrophenyl)butanoate Chemical compound CCOC(=O)CCC(O)C1=CC=CC=C1[N+]([O-])=O MQZTWBSNIOUVKB-UHFFFAOYSA-N 0.000 description 3
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- MDYHWQQHEWDJKR-UHFFFAOYSA-N (5-methyl-1,2-oxazol-3-yl)methanol Chemical compound CC1=CC(CO)=NO1 MDYHWQQHEWDJKR-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- HRVRAYIYXRVAPR-UHFFFAOYSA-N 1,3,4,5-tetrahydro-1-benzazepin-2-one Chemical compound N1C(=O)CCCC2=CC=CC=C21 HRVRAYIYXRVAPR-UHFFFAOYSA-N 0.000 description 2
- SSRIYPPJKDWTLD-UHFFFAOYSA-N 10-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-6-methyl-9h-imidazo[1,5-a]pyrimido[5,4-d][1]benzazepine Chemical compound CC1=NCN(C=23)C1=CC1=CN=CN=C1C3=CC=CC=2C(ON=1)=NC=1C1CC1 SSRIYPPJKDWTLD-UHFFFAOYSA-N 0.000 description 2
- GZUWCGMDZGHCBZ-UHFFFAOYSA-N 10-bromo-2-[(4-methoxyphenyl)methyl]-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1=CC(OC)=CC=C1CC1=NC=C(CC(=O)NC=2C3=CC(Br)=CC=2)C3=N1 GZUWCGMDZGHCBZ-UHFFFAOYSA-N 0.000 description 2
- ZMLSAYFUYICYSA-UHFFFAOYSA-N 10-bromo-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1C(=O)CC2=CN=CN=C2C2=CC(Br)=CC=C21 ZMLSAYFUYICYSA-UHFFFAOYSA-N 0.000 description 2
- VTIYPXJWSVDIDL-UHFFFAOYSA-N 10-chloro-2-(1h-indol-3-ylmethyl)-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC(Cl)=CC=C3NC(=O)CC2=CN=C1CC1=CNC2=CC=CC=C12 VTIYPXJWSVDIDL-UHFFFAOYSA-N 0.000 description 2
- ZOTLUPHXEQCCBO-UHFFFAOYSA-N 10-chloro-2-[(4-methoxyphenyl)methyl]-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1=CC(OC)=CC=C1CC1=NC=C(CC(=O)NC=2C3=CC(Cl)=CC=2)C3=N1 ZOTLUPHXEQCCBO-UHFFFAOYSA-N 0.000 description 2
- FBNCXUFOEYIGHJ-UHFFFAOYSA-N 10-chloro-2-methyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(Cl)C=C2C2=NC(C)=NC=C21 FBNCXUFOEYIGHJ-UHFFFAOYSA-N 0.000 description 2
- GHBKKPSEJBPINY-UHFFFAOYSA-N 10-chloro-2-propan-2-yl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(Cl)C=C2C2=NC(C(C)C)=NC=C21 GHBKKPSEJBPINY-UHFFFAOYSA-N 0.000 description 2
- DVOFZQFFSNACDD-UHFFFAOYSA-N 10-fluoro-2-(1h-indol-3-ylmethyl)-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC(F)=CC=C3NC(=O)CC2=CN=C1CC1=CNC2=CC=CC=C12 DVOFZQFFSNACDD-UHFFFAOYSA-N 0.000 description 2
- HPDCYKAGSWBSCB-UHFFFAOYSA-N 10-fluoro-2-[(4-methoxyphenyl)methyl]-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1=CC(OC)=CC=C1CC1=NC=C(CC(=O)NC=2C3=CC(F)=CC=2)C3=N1 HPDCYKAGSWBSCB-UHFFFAOYSA-N 0.000 description 2
- ZYKHDYHESBDKIL-UHFFFAOYSA-N 10-fluoro-2-methyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(F)C=C2C2=NC(C)=NC=C21 ZYKHDYHESBDKIL-UHFFFAOYSA-N 0.000 description 2
- HDFDLOSCTUYTKC-UHFFFAOYSA-N 10-fluoro-2-propan-2-yl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(F)C=C2C2=NC(C(C)C)=NC=C21 HDFDLOSCTUYTKC-UHFFFAOYSA-N 0.000 description 2
- XTMOLVZFEGVFFH-UHFFFAOYSA-N 10-fluoro-2-propyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(F)C=C2C2=NC(CCC)=NC=C21 XTMOLVZFEGVFFH-UHFFFAOYSA-N 0.000 description 2
- LMWHZYHKPZVCKJ-UHFFFAOYSA-N 10-methyl-2-propan-2-yl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(C)C=C2C2=NC(C(C)C)=NC=C21 LMWHZYHKPZVCKJ-UHFFFAOYSA-N 0.000 description 2
- GJIQQVGWSLRAIJ-UHFFFAOYSA-N 10-methyl-2-propyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(C)C=C2C2=NC(CCC)=NC=C21 GJIQQVGWSLRAIJ-UHFFFAOYSA-N 0.000 description 2
- DVCQPHCVVHCSCC-UHFFFAOYSA-N 2,10-dimethyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1C(=O)CC2=CN=C(C)N=C2C2=CC(C)=CC=C21 DVCQPHCVVHCSCC-UHFFFAOYSA-N 0.000 description 2
- ARDGQYVTLGUJII-UHFFFAOYSA-N 2,2-dimethylpropanimidamide;hydrochloride Chemical compound Cl.CC(C)(C)C(N)=N ARDGQYVTLGUJII-UHFFFAOYSA-N 0.000 description 2
- RCCJVVAAYHKULN-UHFFFAOYSA-N 2,9,10-trimethyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC(C)=C(C)C=C2C2=NC(C)=NC=C21 RCCJVVAAYHKULN-UHFFFAOYSA-N 0.000 description 2
- GXFFJBLDPMTOJJ-UHFFFAOYSA-N 2-(1h-indol-3-yl)ethanimidamide Chemical compound C1=CC=C2C(CC(=N)N)=CNC2=C1 GXFFJBLDPMTOJJ-UHFFFAOYSA-N 0.000 description 2
- IPGINVKCFFJJKB-UHFFFAOYSA-N 2-(1h-indol-3-ylmethyl)-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC=CC=C3NC(=O)CC2=CN=C1CC1=CNC2=CC=CC=C12 IPGINVKCFFJJKB-UHFFFAOYSA-N 0.000 description 2
- JVFGVFRIJQTIOQ-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1=CC(OC)=CC=C1CC1=NC=C(CC(=O)NC=2C3=CC=CC=2)C3=N1 JVFGVFRIJQTIOQ-UHFFFAOYSA-N 0.000 description 2
- MGCIFZWXETZGCU-UHFFFAOYSA-N 2-cyclopropyl-10-fluoro-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC(F)=CC=C3NC(=O)CC2=CN=C1C1CC1 MGCIFZWXETZGCU-UHFFFAOYSA-N 0.000 description 2
- SONFPVJKKZCRER-UHFFFAOYSA-N 2-cyclopropyl-10-methyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC(C)=CC=C3NC(=O)CC2=CN=C1C1CC1 SONFPVJKKZCRER-UHFFFAOYSA-N 0.000 description 2
- UGCFWOLFLKDSCX-UHFFFAOYSA-N 2-cyclopropyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC=CC=C3NC(=O)CC2=CN=C1C1CC1 UGCFWOLFLKDSCX-UHFFFAOYSA-N 0.000 description 2
- JXOLRVOPIJGLIL-UHFFFAOYSA-N 2-phenyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC=CC=C3NC(=O)CC2=CN=C1C1=CC=CC=C1 JXOLRVOPIJGLIL-UHFFFAOYSA-N 0.000 description 2
- CKZXJWRRHLEBCD-UHFFFAOYSA-N 2-propan-2-yl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=CC=C2C2=NC(C(C)C)=NC=C21 CKZXJWRRHLEBCD-UHFFFAOYSA-N 0.000 description 2
- ZSJPNQKUGABWCF-UHFFFAOYSA-N 2-tert-butyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=CC=C2C2=NC(C(C)(C)C)=NC=C21 ZSJPNQKUGABWCF-UHFFFAOYSA-N 0.000 description 2
- WRXIHCIAXHCRIS-UHFFFAOYSA-N 6-methyl-9h-imidazo[1,5-a]pyrimido[5,4-d][1]benzazepine-10-carboxylic acid Chemical compound C=1C2=CN=CN=C2C2=CC=CC(C(O)=O)=C2N2CN=C(C)C2=1 WRXIHCIAXHCRIS-UHFFFAOYSA-N 0.000 description 2
- AUDMZFAMLPFLHP-UHFFFAOYSA-N 6-methyl-9h-imidazo[1,5-a]pyrimido[5,4-d][1]benzazepine-10-carboxylic acid ethyl ester Chemical compound C12=NC=NC=C2C=C2C(C)=NCN2C2=C1C=CC=C2C(=O)OCC AUDMZFAMLPFLHP-UHFFFAOYSA-N 0.000 description 2
- XSSMUNSMBSUOAW-UHFFFAOYSA-N 7-bromo-3,4-dihydro-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)CCC(=O)C2=CC(Br)=CC=C21 XSSMUNSMBSUOAW-UHFFFAOYSA-N 0.000 description 2
- JLWCRRWZBRCFDJ-UHFFFAOYSA-N 7-fluoro-3,4-dihydro-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)CCC(=O)C2=CC(F)=CC=C21 JLWCRRWZBRCFDJ-UHFFFAOYSA-N 0.000 description 2
- YQKWATQGDSRPFK-UHFFFAOYSA-N 7-methyl-3,4-dihydro-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)CCC(=O)C2=CC(C)=CC=C21 YQKWATQGDSRPFK-UHFFFAOYSA-N 0.000 description 2
- BYSKMYBTAQYSMU-UHFFFAOYSA-N 9,10-dimethyl-2-propyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC(C)=C(C)C=C2C2=NC(CCC)=NC=C21 BYSKMYBTAQYSMU-UHFFFAOYSA-N 0.000 description 2
- UKHFPVCOXBJPIN-UHFFFAOYSA-N 9H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester Chemical compound N1C2=CC=CC=C2C2=C1C=NC(C(=O)OC)=C2 UKHFPVCOXBJPIN-UHFFFAOYSA-N 0.000 description 2
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 2
- JLZGETUJBONFFE-UHFFFAOYSA-N C[Si](C)(C)OC(CCC(=O)O)C1=CC=CC=C1[N+](=O)[O-] Chemical compound C[Si](C)(C)OC(CCC(=O)O)C1=CC=CC=C1[N+](=O)[O-] JLZGETUJBONFFE-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- 235000019759 Maize starch Nutrition 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- XWLKNNDVBNZCLK-UHFFFAOYSA-N ethyl 17-bromo-3-[(4-methoxyphenyl)methyl]-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Br)C(=NC=1)CC1=CC=C(C=C1)OC XWLKNNDVBNZCLK-UHFFFAOYSA-N 0.000 description 2
- VDGJXVHYFJJTHS-UHFFFAOYSA-N ethyl 17-bromo-3-cyclopropyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Br)C(=NC=1)C1CC1 VDGJXVHYFJJTHS-UHFFFAOYSA-N 0.000 description 2
- CLRNFDMIAIWHHN-UHFFFAOYSA-N ethyl 17-chloro-3-(1H-indol-3-ylmethyl)-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Cl)C(=NC=1)CC1=CNC2=CC=CC=C12 CLRNFDMIAIWHHN-UHFFFAOYSA-N 0.000 description 2
- UDVSNVHNARITJI-UHFFFAOYSA-N ethyl 17-chloro-3-[(4-methoxyphenyl)methyl]-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound ClC1=CC2=C(C=3C(CC=4N2C(=NC4)CC4=CC=C(C=C4)OC)=C(N=CN3)C(=O)OCC)C=C1 UDVSNVHNARITJI-UHFFFAOYSA-N 0.000 description 2
- XRWOCNYLHCUCFO-UHFFFAOYSA-N ethyl 17-chloro-3-methyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Cl)C(=NC=1)C XRWOCNYLHCUCFO-UHFFFAOYSA-N 0.000 description 2
- MPDNQXGOIDQQKG-UHFFFAOYSA-N ethyl 17-fluoro-3-propyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)F)C(=NC=1)CCC MPDNQXGOIDQQKG-UHFFFAOYSA-N 0.000 description 2
- OYQVQWIASIXXRT-UHFFFAOYSA-N ethyl 2,4-dioxopentanoate Chemical compound CCOC(=O)C(=O)CC(C)=O OYQVQWIASIXXRT-UHFFFAOYSA-N 0.000 description 2
- JXVAFPULGWAWJD-UHFFFAOYSA-N ethyl 2-(dimethylaminomethylideneamino)acetate Chemical compound CCOC(=O)CN=CN(C)C JXVAFPULGWAWJD-UHFFFAOYSA-N 0.000 description 2
- ZBOJPKMVQLSLDQ-UHFFFAOYSA-N ethyl 2-[(4-ethoxy-4-oxobutanoyl)amino]-5-methylbenzoate Chemical compound CCOC(=O)CCC(=O)NC1=C(C=C(C=C1)C)C(=O)OCC ZBOJPKMVQLSLDQ-UHFFFAOYSA-N 0.000 description 2
- PKWFESSNWKEZDP-UHFFFAOYSA-N ethyl 2-amino-5-bromobenzoate Chemical compound CCOC(=O)C1=CC(Br)=CC=C1N PKWFESSNWKEZDP-UHFFFAOYSA-N 0.000 description 2
- XWWBMLMEVRIPSX-UHFFFAOYSA-N ethyl 2-amino-5-chlorobenzoate Chemical compound CCOC(=O)C1=CC(Cl)=CC=C1N XWWBMLMEVRIPSX-UHFFFAOYSA-N 0.000 description 2
- HSKOREORSSOUOG-UHFFFAOYSA-N ethyl 2-amino-5-fluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=CC=C1N HSKOREORSSOUOG-UHFFFAOYSA-N 0.000 description 2
- OROMVXLWBWNXIW-UHFFFAOYSA-N ethyl 2-amino-5-methylbenzoate Chemical compound CCOC(=O)C1=CC(C)=CC=C1N OROMVXLWBWNXIW-UHFFFAOYSA-N 0.000 description 2
- FGJKKUHHOQVZBP-UHFFFAOYSA-N ethyl 3,16,17-trimethyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=C(C(=C3)C)C)C(=NC=1)C FGJKKUHHOQVZBP-UHFFFAOYSA-N 0.000 description 2
- QYBKNJDQMSCDER-UHFFFAOYSA-N ethyl 3-cyclopropyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C(=NC=1)C1CC1 QYBKNJDQMSCDER-UHFFFAOYSA-N 0.000 description 2
- BYLSUDQUWFREOE-UHFFFAOYSA-N ethyl 3-propan-2-yl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C(=NC=1)C(C)C BYLSUDQUWFREOE-UHFFFAOYSA-N 0.000 description 2
- HWQPVWLRGKNTBC-UHFFFAOYSA-N ethyl 4-(2-aminophenyl)-4-hydroxybutanoate Chemical compound CCOC(=O)CCC(O)C1=CC=CC=C1N HWQPVWLRGKNTBC-UHFFFAOYSA-N 0.000 description 2
- XWPSASIDUQCXDQ-UHFFFAOYSA-N ethyl 4-(2-aminophenyl)-4-trimethylsilyloxybutanoate Chemical compound CCOC(=O)CCC(O[Si](C)(C)C)c1ccccc1N XWPSASIDUQCXDQ-UHFFFAOYSA-N 0.000 description 2
- HUQGGMPYIPZTPT-UHFFFAOYSA-N ethyl 4-(2-nitrophenyl)-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=CC=C1[N+]([O-])=O HUQGGMPYIPZTPT-UHFFFAOYSA-N 0.000 description 2
- QEBXSTNSRFNZRF-UHFFFAOYSA-N ethyl 4-(2-nitrophenyl)-4-trimethylsilyloxybutanoate Chemical compound CCOC(=O)CCC(O[Si](C)(C)C)c1ccccc1[N+]([O-])=O QEBXSTNSRFNZRF-UHFFFAOYSA-N 0.000 description 2
- ALTMWZHMMIUPGS-UHFFFAOYSA-N ethyl 5-hydroxy-7-methyl-2-oxo-1,3-dihydro-1-benzazepine-4-carboxylate Chemical compound N1C(=O)CC(C(=O)OCC)=C(O)C2=CC(C)=CC=C21 ALTMWZHMMIUPGS-UHFFFAOYSA-N 0.000 description 2
- JDEXFODYDIAIDM-UHFFFAOYSA-N ethyl 7-bromo-5-hydroxy-2-oxo-1,3-dihydro-1-benzazepine-4-carboxylate Chemical compound N1C(=O)CC(C(=O)OCC)=C(O)C2=CC(Br)=CC=C21 JDEXFODYDIAIDM-UHFFFAOYSA-N 0.000 description 2
- OGAJQLVXLWNPBQ-UHFFFAOYSA-N ethyl 7-chloro-5-hydroxy-2-oxo-1,3-dihydro-1-benzazepine-4-carboxylate Chemical compound N1C(=O)CC(C(=O)OCC)=C(O)C2=CC(Cl)=CC=C21 OGAJQLVXLWNPBQ-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 150000003951 lactams Chemical class 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- GYVGXEWAOAAJEU-UHFFFAOYSA-N n,n,4-trimethylaniline Chemical compound CN(C)C1=CC=C(C)C=C1 GYVGXEWAOAAJEU-UHFFFAOYSA-N 0.000 description 2
- HRLOEWVFPPXRGD-UHFFFAOYSA-N n,n-dimethyl-n'-[(5-methyl-1,2-oxazol-3-yl)methyl]methanimidamide Chemical compound CN(C)C=NCC=1C=C(C)ON=1 HRLOEWVFPPXRGD-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 230000003405 preventing effect Effects 0.000 description 2
- ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 1
- WWVGXWRJWMUFSY-UHFFFAOYSA-N 1-benzazepin-5-one Chemical compound O=C1C=CC=NC2=CC=CC=C12 WWVGXWRJWMUFSY-UHFFFAOYSA-N 0.000 description 1
- ZUZNFSDKKQKOHL-UHFFFAOYSA-N 10-bromo-2-cyclopropyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C3=CC(Br)=CC=C3NC(=O)CC2=CN=C1C1CC1 ZUZNFSDKKQKOHL-UHFFFAOYSA-N 0.000 description 1
- PBURBKRMPRQMOT-UHFFFAOYSA-N 17-chloro-3-propan-2-yl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylic acid Chemical compound ClC1=CC2=C(C=3C(CC=4N2C(=NC=4)C(C)C)=C(N=CN=3)C(=O)O)C=C1 PBURBKRMPRQMOT-UHFFFAOYSA-N 0.000 description 1
- JGWNRBMSWVYMRZ-UHFFFAOYSA-N 17-fluoro-3-propyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylic acid Chemical compound FC1=CC2=C(C=3C(CC=4N2C(=NC=4)CCC)=C(N=CN=3)C(=O)O)C=C1 JGWNRBMSWVYMRZ-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- OPFAHOSSSDHZRK-UHFFFAOYSA-N 2-(1h-indol-3-ylmethyl)-9,10-dimethyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1=C2C=3C=C(C)C(C)=CC=3NC(=O)CC2=CN=C1CC1=CNC2=CC=CC=C12 OPFAHOSSSDHZRK-UHFFFAOYSA-N 0.000 description 1
- XWSOZUAQVGZCKZ-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-9,10-dimethyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1=CC(OC)=CC=C1CC1=NC=C(CC(=O)NC=2C3=CC(C)=C(C)C=2)C3=N1 XWSOZUAQVGZCKZ-UHFFFAOYSA-N 0.000 description 1
- CUKXRHLWPSBCTI-UHFFFAOYSA-N 2-amino-5-bromobenzoic acid Chemical compound NC1=CC=C(Br)C=C1C(O)=O CUKXRHLWPSBCTI-UHFFFAOYSA-N 0.000 description 1
- NBUUUJWWOARGNW-UHFFFAOYSA-N 2-amino-5-methylbenzoic acid Chemical compound CC1=CC=C(N)C(C(O)=O)=C1 NBUUUJWWOARGNW-UHFFFAOYSA-N 0.000 description 1
- PAEJWWUKYONKRE-UHFFFAOYSA-N 2-methyl-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=CC=C2C2=NC(C)=NC=C21 PAEJWWUKYONKRE-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- UNHOVIPXYDEGAP-UHFFFAOYSA-N 2-tert-butyl-10-chloro-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(Cl)C=C2C2=NC(C(C)(C)C)=NC=C21 UNHOVIPXYDEGAP-UHFFFAOYSA-N 0.000 description 1
- AZEJQGKRGWUVTK-UHFFFAOYSA-N 2-tert-butyl-10-fluoro-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound C1C(=O)NC2=CC=C(F)C=C2C2=NC(C(C)(C)C)=NC=C21 AZEJQGKRGWUVTK-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- XPAPXXWVFZQVPH-UHFFFAOYSA-N 5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one Chemical compound N1C(=O)CC2=CN=CN=C2C2=CC=CC=C21 XPAPXXWVFZQVPH-UHFFFAOYSA-N 0.000 description 1
- BNMPIJWVMVNSRD-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NO1 BNMPIJWVMVNSRD-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- VBDSIAKHUIKYJJ-UHFFFAOYSA-N 7,8-dimethyl-3,4-dihydro-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)CCC(=O)C2=C1C=C(C)C(C)=C2 VBDSIAKHUIKYJJ-UHFFFAOYSA-N 0.000 description 1
- YRUGIDNPYWLNBV-UHFFFAOYSA-N 7-chloro-3,4-dihydro-1h-1-benzazepine-2,5-dione Chemical compound N1C(=O)CCC(=O)C2=CC(Cl)=CC=C21 YRUGIDNPYWLNBV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229940084657 Benzodiazepine receptor inverse agonist Drugs 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- SKNBFMOYZIBSMU-UHFFFAOYSA-N CC=1N=CC2=CC(N=C3C(=C2N1)C=C(C(=C3)C)C)=O Chemical compound CC=1N=CC2=CC(N=C3C(=C2N1)C=C(C(=C3)C)C)=O SKNBFMOYZIBSMU-UHFFFAOYSA-N 0.000 description 1
- MRROPEWAOJXNFB-GQCTYLIASA-N CN(C)\C=N\CC(O)=O Chemical compound CN(C)\C=N\CC(O)=O MRROPEWAOJXNFB-GQCTYLIASA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 229940123318 GABA A alpha5 inverse agonist Drugs 0.000 description 1
- 102000017934 GABA-B receptor Human genes 0.000 description 1
- 108060003377 GABA-B receptor Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 239000001828 Gelatine Substances 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
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- NMVVJCLUYUWBSZ-UHFFFAOYSA-N aminomethylideneazanium;chloride Chemical compound Cl.NC=N NMVVJCLUYUWBSZ-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 239000003086 colorant Substances 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- SKQPQABLQADKRZ-UHFFFAOYSA-N ethyl 16,17-dimethyl-3-propyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=C(C(=C3)C)C)C(=NC=1)CCC SKQPQABLQADKRZ-UHFFFAOYSA-N 0.000 description 1
- IWHAHQVFMZOWQJ-UHFFFAOYSA-N ethyl 17-bromo-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Br)C=NC=1 IWHAHQVFMZOWQJ-UHFFFAOYSA-N 0.000 description 1
- WEKFWCFKWGUMPB-UHFFFAOYSA-N ethyl 17-bromo-3-methyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Br)C(=NC=1)C WEKFWCFKWGUMPB-UHFFFAOYSA-N 0.000 description 1
- MPNDLCMUUIQRJI-UHFFFAOYSA-N ethyl 17-chloro-3-cyclopropyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)Cl)C(=NC=1)C1CC1 MPNDLCMUUIQRJI-UHFFFAOYSA-N 0.000 description 1
- OBKHAZPTTDMNLK-UHFFFAOYSA-N ethyl 17-fluoro-3-(1H-indol-3-ylmethyl)-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)F)C(=NC=1)CC1=CNC2=CC=CC=C12 OBKHAZPTTDMNLK-UHFFFAOYSA-N 0.000 description 1
- JZYGPQZLNIDLPD-UHFFFAOYSA-N ethyl 17-fluoro-3-propan-2-yl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)F)C(=NC=1)C(C)C JZYGPQZLNIDLPD-UHFFFAOYSA-N 0.000 description 1
- ZVGXBXGDPXZIKW-UHFFFAOYSA-N ethyl 17-methyl-3-propyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)C)C(=NC=1)CCC ZVGXBXGDPXZIKW-UHFFFAOYSA-N 0.000 description 1
- NONZRSKNFYNZRA-UHFFFAOYSA-N ethyl 2-[(4-ethoxy-4-oxobutanoyl)amino]-5-fluorobenzoate Chemical compound C(C)OC(C1=C(C=CC(=C1)F)NC(CCC(=O)OCC)=O)=O NONZRSKNFYNZRA-UHFFFAOYSA-N 0.000 description 1
- YSBUWJGLBQDUMI-UHFFFAOYSA-N ethyl 2-[(4-ethoxy-4-oxobutanoyl)amino]benzoate Chemical compound CCOC(=O)CCC(=O)NC1=CC=CC=C1C(=O)OCC YSBUWJGLBQDUMI-UHFFFAOYSA-N 0.000 description 1
- KYRKLHZIIIPDJF-UHFFFAOYSA-N ethyl 3,17-dimethyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)C)C(=NC=1)C KYRKLHZIIIPDJF-UHFFFAOYSA-N 0.000 description 1
- MBTFNQSYWDSSKI-UHFFFAOYSA-N ethyl 3-(1H-indol-3-ylmethyl)-16,17-dimethyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=C(C(=C3)C)C)C(=NC=1)CC1=CNC2=CC=CC=C12 MBTFNQSYWDSSKI-UHFFFAOYSA-N 0.000 description 1
- AADAZENBELQHMD-UHFFFAOYSA-N ethyl 3-[(4-methoxyphenyl)methyl]-16,17-dimethyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=C(C(=C3)C)C)C(=NC=1)CC1=CC=C(C=C1)OC AADAZENBELQHMD-UHFFFAOYSA-N 0.000 description 1
- YXNAGZRUSHNALZ-UHFFFAOYSA-N ethyl 3-[(4-methoxyphenyl)methyl]-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C(=NC=1)CC1=CC=C(C=C1)OC YXNAGZRUSHNALZ-UHFFFAOYSA-N 0.000 description 1
- MWCWRHMRAJIUNY-UHFFFAOYSA-N ethyl 3-cyclopropyl-17-fluoro-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)F)C(=NC=1)C1CC1 MWCWRHMRAJIUNY-UHFFFAOYSA-N 0.000 description 1
- BZHRAJKNZFFQNV-UHFFFAOYSA-N ethyl 3-cyclopropyl-17-methyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,8(13),9,11,15,17-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC(=C3)C)C(=NC=1)C1CC1 BZHRAJKNZFFQNV-UHFFFAOYSA-N 0.000 description 1
- DFLAUBXVZVOXOQ-UHFFFAOYSA-N ethyl 3-phenyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C(=NC=1)C1=CC=CC=C1 DFLAUBXVZVOXOQ-UHFFFAOYSA-N 0.000 description 1
- VVNRKQDIMCCSDA-UHFFFAOYSA-N ethyl 3-propyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C(=NC=1)CCC VVNRKQDIMCCSDA-UHFFFAOYSA-N 0.000 description 1
- UUASFEUYYSOQHL-UHFFFAOYSA-N ethyl 3-tert-butyl-2,4,10,12-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),3,5,8(13),9,11,14,16-octaene-9-carboxylate Chemical compound C(C)OC(=O)C=1N=CN=C2C=1CC=1N(C3=C2C=CC=C3)C(=NC=1)C(C)(C)C UUASFEUYYSOQHL-UHFFFAOYSA-N 0.000 description 1
- AKKZWDPNRFZFEX-UHFFFAOYSA-N ethyl 4-(2-aminophenyl)-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=CC=C1N AKKZWDPNRFZFEX-UHFFFAOYSA-N 0.000 description 1
- IBDXUWIRARDNHT-UHFFFAOYSA-N ethyl 5-bromo-2-[(4-ethoxy-4-oxobutanoyl)amino]benzoate Chemical compound CCOC(=O)CCC(=O)NC1=CC=C(Br)C=C1C(=O)OCC IBDXUWIRARDNHT-UHFFFAOYSA-N 0.000 description 1
- KHENELKJMRVNGV-UHFFFAOYSA-N ethyl 5-chloro-2-[(4-ethoxy-4-oxobutanoyl)amino]benzoate Chemical compound C(C)OC(C1=C(C=CC(=C1)Cl)NC(CCC(=O)OCC)=O)=O KHENELKJMRVNGV-UHFFFAOYSA-N 0.000 description 1
- PLGDATYQXDDDLF-UHFFFAOYSA-N ethyl 5-hydroxy-2-oxo-1,3-dihydro-1-benzazepine-4-carboxylate Chemical compound N1C(=O)CC(C(=O)OCC)=C(O)C2=CC=CC=C21 PLGDATYQXDDDLF-UHFFFAOYSA-N 0.000 description 1
- ADMQMZVVXJWKOH-UHFFFAOYSA-N ethyl 7-fluoro-5-hydroxy-2-oxo-1,3-dihydro-1-benzazepine-4-carboxylate Chemical compound N1C(=O)CC(C(=O)OCC)=C(O)C2=CC(F)=CC=C21 ADMQMZVVXJWKOH-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000008011 inorganic excipient Substances 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- YFKAOVPMZLHAFC-UHFFFAOYSA-N n,n-dimethyl-1,1-bis(methylperoxy)methanamine Chemical compound COOC(N(C)C)OOC YFKAOVPMZLHAFC-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 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
- 239000008012 organic excipient Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 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
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01112222 | 2001-05-18 | ||
| PCT/EP2002/005121 WO2002094834A1 (en) | 2001-05-18 | 2002-05-08 | Imidazo [1,5-a] pyrimido [5,4-d] benzazepine derivatives as gaba a receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK15252003A3 true SK15252003A3 (sk) | 2004-08-03 |
Family
ID=8177471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1525-2003A SK15252003A3 (sk) | 2001-05-18 | 2002-05-08 | Deriváty imidazo[1,5-a]pyrimido[5,4-d][1]benzazepínu ako GABA a modulátory receptora |
Country Status (37)
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2540987T3 (es) | 2004-05-14 | 2015-07-15 | Millennium Pharmaceuticals, Inc. | Métodos para preparar inhibidores de la aurora cinasa |
| AU2005294575B2 (en) * | 2004-10-04 | 2011-11-24 | Millennium Pharmaceuticals, Inc. | Lactam compounds useful as protein kinase inhibitors |
| ES2399439T3 (es) * | 2004-10-20 | 2013-04-01 | F. Hoffmann-La Roche Ag | Derivados de imidazo-benzodiazepina |
| AU2005299031B2 (en) * | 2004-10-20 | 2011-11-10 | F. Hoffmann-La Roche Ag | Halogen substituted benzodiazepine derivatives |
| KR101009860B1 (ko) * | 2005-10-11 | 2011-01-19 | 에프. 호프만-라 로슈 아게 | 이미다조 벤조다이아제핀 유도체 |
| PE20080145A1 (es) * | 2006-03-21 | 2008-02-11 | Janssen Pharmaceutica Nv | Tetrahidro-pirimidoazepinas como moduladores de trpv1 |
| CL2007003244A1 (es) | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| WO2009078999A1 (en) | 2007-12-17 | 2009-06-25 | Janssen Pharmaceutica N.V. | Imidazolo-, oxazolo-, and thiazolopyrimidine modulators of trpv1 |
| CN101735211B (zh) * | 2008-11-04 | 2012-11-14 | 复旦大学 | 2,3-二氢[1,5]苯并噻氮杂*类化合物或其盐在制备GSK-3β抑制剂中的用途 |
| US7998952B2 (en) | 2008-12-05 | 2011-08-16 | Millennium Pharmaceuticals, Inc. | Thiolactams and uses thereof |
| RU2535032C2 (ru) | 2008-12-22 | 2014-12-10 | Милленниум Фармасьютикалз, Инк. | Сочетание ингибиторов аврора киназы и анти-cd 20 антител |
| JO3635B1 (ar) | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
| CA2788774A1 (en) | 2010-02-19 | 2011-08-25 | Millennium Pharmaceuticals, Inc. | Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5h-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate |
| CN101891706B (zh) * | 2010-04-09 | 2013-05-29 | 复旦大学 | 3,4-二氢苯并[f][1,4]噻氮杂*类化合物或其盐及其药物用途 |
| CN102424670A (zh) * | 2011-10-31 | 2012-04-25 | 江苏阿尔法药业有限公司 | 一种合成3-(3-氯丙基)-1,3,4,5-四氢-7,8-二甲氧基-2h-3-苯并氮杂卓-2-酮的方法 |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| US20130303519A1 (en) | 2012-03-20 | 2013-11-14 | Millennium Pharmaceuticals, Inc. | Methods of treating cancer using aurora kinase inhibitors |
| WO2014153509A1 (en) | 2013-03-22 | 2014-09-25 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mtorc 1/2 inhibitors and selective inhibitors of aurora a kinase |
| EP3083569B1 (en) | 2013-12-20 | 2022-01-26 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| JP6987384B2 (ja) | 2015-06-19 | 2021-12-22 | エージンバイオ， インコーポレイテッド | ベンゾジアゼピン誘導体、組成物、および認知障害を処置するための方法 |
| JP2018524292A (ja) | 2015-07-21 | 2018-08-30 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | オーロラキナーゼインヒビターと化学療法剤の投与 |
| US20180170941A1 (en) | 2016-12-19 | 2018-06-21 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US11505555B2 (en) | 2016-12-19 | 2022-11-22 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US11414425B2 (en) | 2018-06-19 | 2022-08-16 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| CN110452172B (zh) * | 2019-08-21 | 2021-03-26 | 爱斯特（成都）生物制药股份有限公司 | 一种苯并己内酰胺的合成方法 |
| CN112159411A (zh) * | 2020-10-15 | 2021-01-01 | 南京工业大学 | 一种三氟甲基取代嘧啶并[1,3]二氮杂*化合物及其制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2607503B1 (fr) * | 1986-12-02 | 1989-02-24 | Rhone Poulenc Sante | Nouveaux derives de l'isoindolinone, leur preparation et les compositions pharmaceutiques qui les contiennent |
| TW201311B (https=) | 1991-06-17 | 1993-03-01 | Hoffmann La Roche | |
| RU2119496C1 (ru) * | 1992-04-14 | 1998-09-27 | Научно-исследовательский институт фармакологии Российской академии медицинских наук | Производные n-ацилпролилдипептидов |
| FR2728902B1 (fr) * | 1994-12-29 | 1997-01-31 | Synthelabo | Derives d'acide 8-oxo-5,8-dihydro-6h-dibenzo(a,g)quinolizine-13-propanoique, leur preparation et leur application en therapeutique |
| WO1999043682A1 (en) * | 1998-02-26 | 1999-09-02 | Neurogen Corporation | 2-(het-)aryl-4-(cyclic amino substituted) heteroaryl fused pyridine derivatives, their preparation and their use as (ant-)agonists for gaba (a) brain receptors |
| US6177569B1 (en) * | 1998-08-25 | 2001-01-23 | Neurogen Corporation | Oxo-pyridoimidazole-carboxamides: GABA brain receptor ligands |
| FR2783828B1 (fr) | 1998-09-29 | 2000-11-10 | Synthelabo | Derives d'acide 5,6-dihydro-4h-imidazo[1,2-a][1] benzazepine -1-acetique, leur preparation et leur application en therapeutique |
| CN1390217A (zh) | 1999-11-12 | 2003-01-08 | 神经原公司 | 二环和三环杂芳族化合物 |
| TWI239333B (en) | 2000-11-16 | 2005-09-11 | Hoffmann La Roche | Benzodiazepine derivatives as GABA A receptor modulators |
-
2002
- 2002-04-09 US US10/118,584 patent/US6686352B2/en not_active Expired - Fee Related
- 2002-05-08 YU YU90003A patent/YU90003A/sh unknown
- 2002-05-08 DE DE60202147T patent/DE60202147T2/de not_active Expired - Lifetime
- 2002-05-08 PL PL02366846A patent/PL366846A1/xx not_active Application Discontinuation
- 2002-05-08 PT PT02771640T patent/PT1399448E/pt unknown
- 2002-05-08 WO PCT/EP2002/005121 patent/WO2002094834A1/en not_active Ceased
- 2002-05-08 DK DK02771640T patent/DK1399448T3/da active
- 2002-05-08 CN CNB028101774A patent/CN1230436C/zh not_active Expired - Fee Related
- 2002-05-08 SI SI200230055T patent/SI1399448T1/xx unknown
- 2002-05-08 EP EP02771640A patent/EP1399448B1/en not_active Expired - Lifetime
- 2002-05-08 RU RU2003136078/04A patent/RU2287531C2/ru not_active IP Right Cessation
- 2002-05-08 HR HR20030890A patent/HRP20030890A2/xx not_active Application Discontinuation
- 2002-05-08 AT AT02771640T patent/ATE283857T1/de not_active IP Right Cessation
- 2002-05-08 CA CA002446903A patent/CA2446903C/en not_active Expired - Fee Related
- 2002-05-08 IL IL15857202A patent/IL158572A0/xx unknown
- 2002-05-08 AU AU2002338898A patent/AU2002338898B2/en not_active Ceased
- 2002-05-08 JP JP2002591507A patent/JP4068466B2/ja not_active Expired - Fee Related
- 2002-05-08 SK SK1525-2003A patent/SK15252003A3/sk unknown
- 2002-05-08 CZ CZ20033355A patent/CZ20033355A3/cs unknown
- 2002-05-08 ES ES02771640T patent/ES2232778T3/es not_active Expired - Lifetime
- 2002-05-08 MX MXPA03010529A patent/MXPA03010529A/es active IP Right Grant
- 2002-05-08 BR BR0209859-8A patent/BR0209859A/pt not_active IP Right Cessation
- 2002-05-08 NZ NZ529097A patent/NZ529097A/en unknown
- 2002-05-08 KR KR10-2003-7015036A patent/KR100533406B1/ko not_active Expired - Fee Related
- 2002-05-08 HU HU0400743A patent/HUP0400743A3/hu unknown
- 2002-05-14 JO JO200243A patent/JO2297B1/en active
- 2002-05-15 TW TW091110162A patent/TWI251489B/zh not_active IP Right Cessation
- 2002-05-15 PA PA20028545201A patent/PA8545201A1/es unknown
- 2002-05-16 GT GT200200087A patent/GT200200087A/es unknown
- 2002-05-16 PE PE2002000413A patent/PE20030041A1/es not_active Application Discontinuation
- 2002-05-16 AR ARP020101805A patent/AR033753A1/es not_active Application Discontinuation
- 2002-05-17 MY MYPI20021808A patent/MY127570A/en unknown
-
2003
- 2003-10-23 IL IL158572A patent/IL158572A/en not_active IP Right Cessation
- 2003-10-31 ZA ZA200308544A patent/ZA200308544B/en unknown
- 2003-11-14 MA MA27398A patent/MA27024A1/fr unknown
- 2003-11-17 EC EC2003004851A patent/ECSP034851A/es unknown
- 2003-11-17 NO NO20035104A patent/NO20035104L/no not_active Application Discontinuation
- 2003-11-18 BG BG108369A patent/BG108369A/bg unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK15252003A3 (sk) | Deriváty imidazo[1,5-a]pyrimido[5,4-d][1]benzazepínu ako GABA a modulátory receptora | |
| AU2002338898A1 (en) | Imidazo [1,5-A] pyrimido [5,4-D] benzazepine derivatives as GABA A receptor modulators | |
| JP4088151B2 (ja) | Ｇａｂａａ受容体モデュレーターとしてのベンゾジアゼピン誘導体 | |
| JP2690282B2 (ja) | イミダゾジアゼピン | |
| KR20070088621A (ko) | 코르티코트로핀-방출 인자 (ｃｒｆ) 수용체 길항제로서유용한 피라졸로(1,5-알파)피리미디닐 유도체 | |
| AU2002217007A1 (en) | Benzodiazepine derivatives as GABA A receptor modulators | |
| CA2069382A1 (en) | Imidazodiazepine | |
| AU2005299032B2 (en) | Imidazo-benzodiazepine derivatives | |
| JP2011513326A (ja) | 疼痛症候群および他の障害の治療法 | |
| NZ554556A (en) | Halogen substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepines | |
| PL177224B1 (pl) | Nowy związek, pochodna imidazoazepiny, środek farmaceutyczny i sposób wytwarzania pochodnej imidazoazepiny |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FB9A | Suspension of patent application procedure |