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
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- 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
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- 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
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- 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
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
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- MDYHWQQHEWDJKR-UHFFFAOYSA-N (5-methyl-1,2-oxazol-3-yl)methanol Chemical compound CC1=CC(CO)=NO1 MDYHWQQHEWDJKR-UHFFFAOYSA-N 0.000 description 2
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- 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
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- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
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- 230000001149 cognitive effect Effects 0.000 description 2
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- 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
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- 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
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- 239000012286 potassium permanganate Substances 0.000 description 2
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- 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
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- 239000012279 sodium borohydride Substances 0.000 description 2
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- 230000019771 cognition Effects 0.000 description 1
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- 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
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- 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
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- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
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- 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
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- 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 |
|---|---|---|---|---|
| AU2005243175B2 (en) | 2004-05-14 | 2011-12-01 | Millennium Pharmaceuticals, Inc. | Compounds and methods for inhibiting mitotic progression by inhibition of Aurora kinase |
| CN102766142A (zh) * | 2004-10-04 | 2012-11-07 | 千禧药品公司 | 有效作为蛋白激酶抑制剂的内酰胺化合物 |
| AU2005299031B2 (en) | 2004-10-20 | 2011-11-10 | F. Hoffmann-La Roche Ag | Halogen substituted benzodiazepine derivatives |
| MX2007004639A (es) * | 2004-10-20 | 2007-06-08 | Hoffmann La Roche | Derivados de imidazo-benzodiazepina. |
| BRPI0617204A2 (pt) | 2005-10-11 | 2011-07-19 | Hoffmann La Roche | derivados de imidazo benzodiazepina |
| 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 |
| JP5684719B2 (ja) * | 2008-12-05 | 2015-03-18 | 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． | Ｐｌｋ阻害剤としての５，７−ジヒドロ−６ｈ−ピリミド［５、−４ｄ］［１］ベンゾアゼピン−６−チオン |
| 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 |
| BR112012020557A8 (pt) | 2010-02-19 | 2018-01-02 | Millennium Pharm Inc | formas cristalinas de 4-{[9-cloro-7-(2-flúor-6-metoifenil)-5h-pirimido[5,4-d][2]benzazepin-2-il]amino}-2-metoxibenzoato de sódio |
| 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 |
| NZ760341A (en) * | 2013-12-20 | 2021-12-24 | Agenebio Inc | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| MX392119B (es) | 2015-06-19 | 2025-03-11 | Agenebio Inc | Derivados de benzodiazepina, composiciones y metodos para tratar deterioro cognitivo |
| WO2017015316A1 (en) | 2015-07-21 | 2017-01-26 | Millennium Pharmaceuticals, Inc. | Administration of aurora kinase inhibitor and chemotherapeutic agents |
| US11505555B2 (en) | 2016-12-19 | 2022-11-22 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US20180170941A1 (en) | 2016-12-19 | 2018-06-21 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| CN112601749B (zh) | 2018-06-19 | 2024-03-26 | 艾吉因生物股份有限公司 | 用于治疗认知损害的苯并二氮杂环庚三烯衍生物，组合物和方法 |
| 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 |
| US6166203A (en) * | 1998-02-26 | 2000-12-26 | Neurogen Corporation | Heterocyclic amino substituted heteroaryl fused pyridines; GABA brain receptor ligands |
| 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 |
| CA2388593A1 (en) | 1999-11-12 | 2001-05-17 | Neurogen Corporation | Bicyclic and tricyclic heteroaromatic compounds |
| TWI239333B (en) | 2000-11-16 | 2005-09-11 | Hoffmann La Roche | Benzodiazepine derivatives as GABA A receptor modulators |
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