HU201763B - Process for producing imidazodiazepine derivatives and pharmaceutical compositions comprising such compounds - Google Patents
Process for producing imidazodiazepine derivatives and pharmaceutical compositions comprising such compounds Download PDFInfo
- Publication number
- HU201763B HU201763B HU881085A HU108588A HU201763B HU 201763 B HU201763 B HU 201763B HU 881085 A HU881085 A HU 881085A HU 108588 A HU108588 A HU 108588A HU 201763 B HU201763 B HU 201763B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- methyl
- alkyl
- cycloalkyl
- dihydro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 88
- 238000000034 method Methods 0.000 title claims description 43
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- BMGXAZCDDYTVFV-UHFFFAOYSA-N imidazo[4,5-c]diazepine Chemical class C1=CN=NC2=NC=NC2=C1 BMGXAZCDDYTVFV-UHFFFAOYSA-N 0.000 title claims description 4
- -1 3-hydroxy-3-methyl-1-butynyl Chemical group 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- YZPAKBGVJIVPEU-UHFFFAOYSA-N 1,2-benzodiazepin-6-one Chemical compound N1=NC=CC=C2C(=O)C=CC=C21 YZPAKBGVJIVPEU-UHFFFAOYSA-N 0.000 claims description 32
- KSSXNHGPIDAUAS-UHFFFAOYSA-N 1,4-benzodiazepin-6-one Chemical compound N1=CC=NC=C2C(=O)C=CC=C21 KSSXNHGPIDAUAS-UHFFFAOYSA-N 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 239000007858 starting material Substances 0.000 claims description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 26
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 13
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 239000011630 iodine Substances 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 102000004300 GABA-A Receptors Human genes 0.000 claims description 10
- 108090000839 GABA-A Receptors Proteins 0.000 claims description 10
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 206010029897 Obsessive thoughts Diseases 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 239000012433 hydrogen halide Substances 0.000 claims description 6
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 6
- GXGJIOMUZAGVEH-UHFFFAOYSA-N Chamazulene Chemical group CCC1=CC=C(C)C2=CC=C(C)C2=C1 GXGJIOMUZAGVEH-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 230000001773 anti-convulsant effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- MGWQSZRZJDZADX-UHFFFAOYSA-N 7-chloro-5-methyl-3-prop-1-ynyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound C1N(C)C(=O)C2=C(Cl)C=CC=C2N2C=NC(C#CC)=C21 MGWQSZRZJDZADX-UHFFFAOYSA-N 0.000 claims description 4
- 239000001961 anticonvulsive agent Substances 0.000 claims description 4
- 229960003965 antiepileptics Drugs 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- KUWLYYUCJPOHEX-UHFFFAOYSA-N 5-methyl-3-prop-1-ynyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound C1N(C)C(=O)C2=CC=CC=C2N2C=NC(C#CC)=C21 KUWLYYUCJPOHEX-UHFFFAOYSA-N 0.000 claims description 3
- 239000002249 anxiolytic agent Substances 0.000 claims description 3
- 230000000949 anxiolytic effect Effects 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 239000003158 myorelaxant agent Substances 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000004799 sedative–hypnotic effect Effects 0.000 claims description 2
- 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 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 3
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 claims 1
- 150000001924 cycloalkanes Chemical class 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 333
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 219
- 239000011541 reaction mixture Substances 0.000 description 87
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
- 239000000203 mixture Substances 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 62
- 239000000741 silica gel Substances 0.000 description 61
- 229910002027 silica gel Inorganic materials 0.000 description 61
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 45
- 238000001953 recrystallisation Methods 0.000 description 42
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 41
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 40
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 33
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- 238000010992 reflux Methods 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 25
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 21
- XBBSCQFBTXPTRV-UHFFFAOYSA-N 1,2-benzodiazepin-9-one Chemical compound C1=CC=NN=C2C(=O)C=CC=C21 XBBSCQFBTXPTRV-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 14
- CEBKHWWANWSNTI-UHFFFAOYSA-N 2-methylbut-3-yn-2-ol Chemical compound CC(C)(O)C#C CEBKHWWANWSNTI-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- IEZFHFAOJFVULZ-UHFFFAOYSA-N 1,4-benzodiazepin-9-one Chemical compound C1=NC=CN=C2C(=O)C=CC=C21 IEZFHFAOJFVULZ-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 239000003960 organic solvent Substances 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 229960001701 chloroform Drugs 0.000 description 8
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- BDQWLNCGPHMZCO-UHFFFAOYSA-N 7-chloro-3-iodo-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(I)N=CN2C2=CC=CC(Cl)=C21 BDQWLNCGPHMZCO-UHFFFAOYSA-N 0.000 description 6
- ISEMTBIUNZHCMN-UHFFFAOYSA-N 8-fluoro-3-iodo-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(I)N=CN2C2=CC=C(F)C=C21 ISEMTBIUNZHCMN-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 6
- 235000019345 sodium thiosulphate Nutrition 0.000 description 6
- 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 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 229960003529 diazepam Drugs 0.000 description 5
- 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 5
- CVLAEJNQNKXNNN-UHFFFAOYSA-N diazepin-4-one Chemical compound O=C1C=CC=NN=C1 CVLAEJNQNKXNNN-UHFFFAOYSA-N 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- SXYFAZGVNNYGJQ-UHFFFAOYSA-M chloromethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCl)C1=CC=CC=C1 SXYFAZGVNNYGJQ-UHFFFAOYSA-M 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- CBKIDHHLDJSTJB-UHFFFAOYSA-N 1,2-benzodiazepine-1-carbaldehyde Chemical compound O=CN1N=CC=CC2=CC=CC=C12 CBKIDHHLDJSTJB-UHFFFAOYSA-N 0.000 description 3
- BQPUZODTKSPSQX-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carbaldehyde Chemical compound O=CC1=NNc2ccccc2C=C1 BQPUZODTKSPSQX-UHFFFAOYSA-N 0.000 description 3
- GXZSASLDJRWQSM-UHFFFAOYSA-N 3-ethynyl-8-fluoro-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(C#C)N=CN2C2=CC=C(F)C=C21 GXZSASLDJRWQSM-UHFFFAOYSA-N 0.000 description 3
- RASWBYHXNFPUSM-UHFFFAOYSA-N 7-chloro-3-(3-hydroxy-3-methylbut-1-ynyl)-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(C#CC(C)(C)O)N=CN2C2=CC=CC(Cl)=C21 RASWBYHXNFPUSM-UHFFFAOYSA-N 0.000 description 3
- IOFWDXJBVONBLF-UHFFFAOYSA-N 7-chloro-3-ethynyl-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(C#C)N=CN2C2=CC=CC(Cl)=C21 IOFWDXJBVONBLF-UHFFFAOYSA-N 0.000 description 3
- MSNVESLISHTIRS-UHFFFAOYSA-N 9h-pyrrolo[2,1-c][1,4]benzodiazepine Chemical compound N1=C2C=CC=CC2=CN2CC=CC2=C1 MSNVESLISHTIRS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- IKWKJIWDLVYZIY-UHFFFAOYSA-M butyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCC)C1=CC=CC=C1 IKWKJIWDLVYZIY-UHFFFAOYSA-M 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DGLHLIWXYSGYBI-UHFFFAOYSA-N 1-chloro-2-ethynylbenzene Chemical group ClC1=CC=CC=C1C#C DGLHLIWXYSGYBI-UHFFFAOYSA-N 0.000 description 2
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- 125000006023 1-pentenyl group Chemical group 0.000 description 2
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 2
- MZHUTGQZAZLFKW-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxylic acid Chemical compound C1=CC(C(=O)O)=NNC2=CC=CC=C21 MZHUTGQZAZLFKW-UHFFFAOYSA-N 0.000 description 2
- SPVSGXHYZOLHFK-UHFFFAOYSA-N 1H-1,4-benzodiazepine-3-carbaldehyde Chemical compound N1C=C(N=CC2=C1C=CC=C2)C=O SPVSGXHYZOLHFK-UHFFFAOYSA-N 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- KWPQTFXULUUCGD-UHFFFAOYSA-N 3,4,5,7,8,9,10,10a-octahydropyrido[1,2-a][1,4]diazepine Chemical compound C1CCN=CC2CCCCN21 KWPQTFXULUUCGD-UHFFFAOYSA-N 0.000 description 2
- ACGJCWCDKDAPOW-UHFFFAOYSA-N 3-(hydroxymethyl)-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(CO)N=CN2C2=CC=CC=C21 ACGJCWCDKDAPOW-UHFFFAOYSA-N 0.000 description 2
- AYCJXXHQIZZKPO-UHFFFAOYSA-N 3-iodo-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(I)N=CN2C2=CC=CC=C21 AYCJXXHQIZZKPO-UHFFFAOYSA-N 0.000 description 2
- SUAPJBZNGZHZDB-UHFFFAOYSA-N 5,7-dimethyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid Chemical compound O=C1N(C)CC2=C(C(O)=O)N=CN2C2=CC=CC(C)=C21 SUAPJBZNGZHZDB-UHFFFAOYSA-N 0.000 description 2
- LHRGFWSQQCJCIL-UHFFFAOYSA-N 5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carbaldehyde Chemical compound O=C1N(C)CC2=C(C=O)N=CN2C2=CC=CC=C21 LHRGFWSQQCJCIL-UHFFFAOYSA-N 0.000 description 2
- HBKFKXDJVGHDGJ-UHFFFAOYSA-N 7-bromo-3-iodo-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(I)N=CN2C2=CC=CC(Br)=C21 HBKFKXDJVGHDGJ-UHFFFAOYSA-N 0.000 description 2
- YCEXHQCDNAVBSU-UHFFFAOYSA-N 7-chloro-3-(3-hydroxyprop-1-ynyl)-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(C#CCO)N=CN2C2=CC=CC(Cl)=C21 YCEXHQCDNAVBSU-UHFFFAOYSA-N 0.000 description 2
- LVHIDPBOMWJGGE-UHFFFAOYSA-N 7-chloro-8-fluoro-3-iodo-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(I)N=CN2C2=CC=C(F)C(Cl)=C21 LVHIDPBOMWJGGE-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 150000008050 dialkyl sulfates Chemical class 0.000 description 2
- VKFAUCPBMAGVRG-UHFFFAOYSA-N dipivefrin hydrochloride Chemical compound [Cl-].C[NH2+]CC(O)C1=CC=C(OC(=O)C(C)(C)C)C(OC(=O)C(C)(C)C)=C1 VKFAUCPBMAGVRG-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- SDWDYYNZDCAYLF-UHFFFAOYSA-N imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N=CC2=CN=CN2C2=CC=CC=C12 SDWDYYNZDCAYLF-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- HNDGEYCCZGRMTN-UHFFFAOYSA-N thieno[3,2-f:4,5-f]bis[1]benzothiophene Chemical compound S1C2=CC=3SC=CC=3C=C2C2=C1C=C(SC=C1)C1=C2 HNDGEYCCZGRMTN-UHFFFAOYSA-N 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
- 125000004665 trialkylsilyl group Chemical group 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- IIGPNJYIQVULOI-JTQLQIEISA-N (7S)-14-bromo-2,4,11-triazatetracyclo[11.4.0.02,6.07,11]heptadeca-1(17),3,5,13,15-pentaen-12-one Chemical compound O=C1N2CCC[C@H]2C2=CN=CN2C2=C1C(Br)=CC=C2 IIGPNJYIQVULOI-JTQLQIEISA-N 0.000 description 1
- CDGPRNWGGDXLOH-LBPRGKRZSA-N (7S)-5-(3-hydroxy-3-methylbut-1-ynyl)-14-thia-2,4,11-triazatetracyclo[11.3.0.02,6.07,11]hexadeca-1(13),3,5,15-tetraen-12-one Chemical compound OC(C#CC=1N=CN2C1[C@H]1N(C(C3=C2C=CS3)=O)CCC1)(C)C CDGPRNWGGDXLOH-LBPRGKRZSA-N 0.000 description 1
- LKPMLIHHNXUBMX-ZDUSSCGKSA-N (7S)-5-(3-hydroxy-3-methylbut-1-ynyl)-16-thia-2,4,11-triazatetracyclo[11.3.0.02,6.07,11]hexadeca-1(13),3,5,14-tetraen-12-one Chemical compound OC(C#CC=1N=CN2C1[C@H]1N(C(C3=C2SC=C3)=O)CCC1)(C)C LKPMLIHHNXUBMX-ZDUSSCGKSA-N 0.000 description 1
- SYOPOFVCXXGUFR-NSHDSACASA-N (s)-11,12,13,13a-tetrahydro-1-iodo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one Chemical compound O=C1C2=CC=CC=C2N2C=NC(I)=C2[C@@H]2CCCN21 SYOPOFVCXXGUFR-NSHDSACASA-N 0.000 description 1
- CPXDKNCLVKDTDJ-JTQLQIEISA-N (s)-8-chloro-11,12,13,13a-tetrahydro-1-iodo-9h-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one Chemical compound O=C1N2CCC[C@H]2C2=C(I)N=CN2C2=C1C(Cl)=CC=C2 CPXDKNCLVKDTDJ-JTQLQIEISA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- GYHCTCSLYWTWJC-UHFFFAOYSA-N 1,4-benzodiazepine-1-carbaldehyde Chemical compound O=CN1C=CN=CC2=CC=CC=C12 GYHCTCSLYWTWJC-UHFFFAOYSA-N 0.000 description 1
- CEHKKWWXELBNPS-UHFFFAOYSA-N 1,4-benzodiazepine-1-carboxylic acid Chemical compound OC(=O)N1C=CN=CC2=CC=CC=C12 CEHKKWWXELBNPS-UHFFFAOYSA-N 0.000 description 1
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- GRBJPHPMYOUMJV-UHFFFAOYSA-N 1-chloro-3-ethynylbenzene Chemical group ClC1=CC=CC(C#C)=C1 GRBJPHPMYOUMJV-UHFFFAOYSA-N 0.000 description 1
- LFZJRTMTKGYJRS-UHFFFAOYSA-N 1-chloro-4-ethynylbenzene Chemical group ClC1=CC=C(C#C)C=C1 LFZJRTMTKGYJRS-UHFFFAOYSA-N 0.000 description 1
- HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 1
- ZASXCTCNZKFDTP-UHFFFAOYSA-N 1-ethynyl-3-methoxybenzene Chemical group COC1=CC=CC(C#C)=C1 ZASXCTCNZKFDTP-UHFFFAOYSA-N 0.000 description 1
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 1
- LQMDOONLLAJAPZ-UHFFFAOYSA-N 1-ethynylcyclopentan-1-ol Chemical compound C#CC1(O)CCCC1 LQMDOONLLAJAPZ-UHFFFAOYSA-N 0.000 description 1
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- CZYSWRBGLXBRBG-UHFFFAOYSA-N 11-iodo-8-methyl-3-thia-1,8,12-triazatricyclo[8.3.0.02,6]trideca-2(6),4,10,12-tetraen-7-one Chemical compound IC=1N=CN2C=1CN(C(C1=C2SC=C1)=O)C CZYSWRBGLXBRBG-UHFFFAOYSA-N 0.000 description 1
- WLODWTPNUWYZKN-UHFFFAOYSA-N 1h-pyrrol-2-ol Chemical compound OC1=CC=CN1 WLODWTPNUWYZKN-UHFFFAOYSA-N 0.000 description 1
- XAMZZEBAJZJERT-UHFFFAOYSA-M 2-oxopropyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC(=O)C)C1=CC=CC=C1 XAMZZEBAJZJERT-UHFFFAOYSA-M 0.000 description 1
- YPAZCZZWCFEQNJ-UHFFFAOYSA-N 3-(2-bromoethynyl)-7-chloro-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(C#CBr)N=CN2C2=CC=CC(Cl)=C21 YPAZCZZWCFEQNJ-UHFFFAOYSA-N 0.000 description 1
- QNRSTGVDCKLAAH-UHFFFAOYSA-N 3-bromo-7-chloro-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(Br)N=CN2C2=CC=CC(Cl)=C21 QNRSTGVDCKLAAH-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- LOYFTTDTFRIMPO-UHFFFAOYSA-N 3-iodo-5,7-dimethyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(I)N=CN2C2=CC=CC(C)=C21 LOYFTTDTFRIMPO-UHFFFAOYSA-N 0.000 description 1
- YACFFSVYSPMSGS-UHFFFAOYSA-N 3-methoxyprop-1-yne Chemical compound COCC#C YACFFSVYSPMSGS-UHFFFAOYSA-N 0.000 description 1
- HRDCVMSNCBAMAM-UHFFFAOYSA-N 3-prop-2-ynoxyprop-1-yne Chemical compound C#CCOCC#C HRDCVMSNCBAMAM-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- RLKQLUHJLXSTIH-UHFFFAOYSA-N 5-methyl-4-oxo-5,6-dihydro-4h-imidazo[1,5-a]thieno[3,2-f][1,4]diazepin-7-carboxylic acid Chemical compound O=C1N(C)CC2=C(C(O)=O)N=CN2C2=C1C=CS2 RLKQLUHJLXSTIH-UHFFFAOYSA-N 0.000 description 1
- HRDUYEJWXXUJCN-UHFFFAOYSA-N 7-bromo-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=CN=CN2C2=CC=CC(Br)=C21 HRDUYEJWXXUJCN-UHFFFAOYSA-N 0.000 description 1
- FVOVLJNUPIZMHZ-WAYWQWQTSA-N 7-chloro-3-[(z)-2-chloroethenyl]-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(\C=C/Cl)N=CN2C2=CC=CC(Cl)=C21 FVOVLJNUPIZMHZ-WAYWQWQTSA-N 0.000 description 1
- DCWNVOXLUFUAPW-UHFFFAOYSA-N 7-chloro-5-methyl-3-(3-methylbut-1-ynyl)-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound C1N(C)C(=O)C2=C(Cl)C=CC=C2N2C=NC(C#CC(C)C)=C21 DCWNVOXLUFUAPW-UHFFFAOYSA-N 0.000 description 1
- ZVOQGXLYIVFAJA-UHFFFAOYSA-N 7-chloro-5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carbaldehyde Chemical compound O=C1N(C)CC2=C(C=O)N=CN2C2=CC=CC(Cl)=C21 ZVOQGXLYIVFAJA-UHFFFAOYSA-N 0.000 description 1
- APMMADOAYKKIHR-UHFFFAOYSA-N 7-chloro-8-fluoro-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=CN=CN2C2=CC=C(F)C(Cl)=C21 APMMADOAYKKIHR-UHFFFAOYSA-N 0.000 description 1
- JKOPERPFQMDETD-UHFFFAOYSA-N 8-fluoro-3-(3-hydroxy-3-methylbut-1-ynyl)-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=C(C#CC(C)(C)O)N=CN2C2=CC=C(F)C=C21 JKOPERPFQMDETD-UHFFFAOYSA-N 0.000 description 1
- JGUGTPMPNXDVNL-UHFFFAOYSA-N 8-fluoro-5-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-6-one Chemical compound O=C1N(C)CC2=CN=CN2C2=CC=C(F)C=C21 JGUGTPMPNXDVNL-UHFFFAOYSA-N 0.000 description 1
- AQANJLIJEGTQHY-UHFFFAOYSA-N 8-fluoro-5-methyl-6-oxo-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carbaldehyde Chemical compound O=C1N(C)CC2=C(C=O)N=CN2C2=CC=C(F)C=C21 AQANJLIJEGTQHY-UHFFFAOYSA-N 0.000 description 1
- HOPHLAMGVMCKIE-UHFFFAOYSA-N 8-methyl-3-thia-1,8,12-triazatricyclo[8.3.0.02,6]trideca-2(6),4,10,12-tetraen-7-one Chemical compound O=C1N(C)CC2=CN=CN2C2=C1C=CS2 HOPHLAMGVMCKIE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- KTRRSFJNORPUDC-UHFFFAOYSA-N Br.N1=NC=CC=C2C1=CC=CC2=O Chemical compound Br.N1=NC=CC=C2C1=CC=CC2=O KTRRSFJNORPUDC-UHFFFAOYSA-N 0.000 description 1
- JDEWVGTUTUWXHF-UHFFFAOYSA-N CCC1=NC(C(O)=O)=C(CN2C)N1C(C=CC=C1)=C1C2=O Chemical compound CCC1=NC(C(O)=O)=C(CN2C)N1C(C=CC=C1)=C1C2=O JDEWVGTUTUWXHF-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 206010014566 Emprosthotonus Diseases 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
- 235000019759 Maize starch Nutrition 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- KMZXZCDZGUCFTA-UHFFFAOYSA-N N=1C=CN=CC=2C=1S(CC=2)=O Chemical compound N=1C=CN=CC=2C=1S(CC=2)=O KMZXZCDZGUCFTA-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000204914 Salmonella enterica subsp. enterica serovar Give Species 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- PPTSBERGOGHCHC-UHFFFAOYSA-N boron lithium Chemical compound [Li].[B] PPTSBERGOGHCHC-UHFFFAOYSA-N 0.000 description 1
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- GKPOMITUDGXOSB-UHFFFAOYSA-N but-3-yn-2-ol Chemical compound CC(O)C#C GKPOMITUDGXOSB-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- JRICKEFXPGZPFZ-UHFFFAOYSA-N chloromethyl(triphenyl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCl)C1=CC=CC=C1 JRICKEFXPGZPFZ-UHFFFAOYSA-N 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- RYGMFSIKBFXOCR-AHCXROLUSA-N copper-60 Chemical compound [60Cu] RYGMFSIKBFXOCR-AHCXROLUSA-N 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([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
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- BIPUHAHGLJKIPK-UHFFFAOYSA-N dicyclopropylmethanone Chemical compound C1CC1C(=O)C1CC1 BIPUHAHGLJKIPK-UHFFFAOYSA-N 0.000 description 1
- 125000004342 dicyclopropylmethyl group Chemical group [H]C1([H])C([H])([H])C1([H])C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- QKDVBBQDDNJDSH-UHFFFAOYSA-N ethanol;formamide Chemical compound CCO.NC=O QKDVBBQDDNJDSH-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- MJEMIOXXNCZZFK-UHFFFAOYSA-N ethylone Chemical compound CCNC(C)C(=O)C1=CC=C2OCOC2=C1 MJEMIOXXNCZZFK-UHFFFAOYSA-N 0.000 description 1
- NPTDXPDGUHAFKC-UHFFFAOYSA-N ethynylcyclopropane Chemical group C#CC1CC1 NPTDXPDGUHAFKC-UHFFFAOYSA-N 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-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
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 230000000269 nucleophilic effect 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
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH88087 | 1987-03-10 | ||
| CH5988 | 1988-01-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT47282A HUT47282A (en) | 1989-02-28 |
| HU201763B true HU201763B (en) | 1990-12-28 |
Family
ID=25683391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU881085A HU201763B (en) | 1987-03-10 | 1988-03-07 | Process for producing imidazodiazepine derivatives and pharmaceutical compositions comprising such compounds |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4863920A (enEXAMPLES) |
| EP (1) | EP0285837B1 (enEXAMPLES) |
| KR (1) | KR880011159A (enEXAMPLES) |
| AU (1) | AU604300B2 (enEXAMPLES) |
| CA (1) | CA1327571C (enEXAMPLES) |
| DE (1) | DE3872559D1 (enEXAMPLES) |
| DK (1) | DK127288A (enEXAMPLES) |
| ES (1) | ES2051781T3 (enEXAMPLES) |
| FI (1) | FI880814A7 (enEXAMPLES) |
| GR (1) | GR3005909T3 (enEXAMPLES) |
| HU (1) | HU201763B (enEXAMPLES) |
| IL (1) | IL85624A0 (enEXAMPLES) |
| MC (1) | MC1918A1 (enEXAMPLES) |
| NO (1) | NO167027C (enEXAMPLES) |
| NZ (1) | NZ223736A (enEXAMPLES) |
| PT (1) | PT86925B (enEXAMPLES) |
| YU (1) | YU47988A (enEXAMPLES) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1327572C (en) * | 1988-08-31 | 1994-03-08 | F. Hoffmann-La Roche Ag | Imidazodiazepine derivatives |
| GB8909700D0 (en) * | 1989-04-27 | 1989-06-14 | Roussel Lab Ltd | Chemical compounds |
| CA2015336A1 (en) * | 1989-05-19 | 1990-11-19 | F. Hoffmann-La Roche Ag | Imidazodiazepines for the treatment of neurological symptoms |
| DE69332929T2 (de) * | 1992-12-04 | 2004-02-26 | Janssen Pharmaceutica N.V. | ANTIALLERGISCHE IMIDAZO[1,2-a]THIENO[2,3-d]AZEPINDERIVATE |
| JP5020819B2 (ja) | 2004-07-16 | 2012-09-05 | プロテオシス・アーゲー | 細胞保護剤としての、ｐａｒｐ及びｓｉｒ調節活性を有するムスカリンアンタゴニスト |
| US20110294791A1 (en) | 2009-01-13 | 2011-12-01 | Proteosys Ag | Pirenzepine as an agent in cancer treatment |
| US11008323B2 (en) | 2015-11-13 | 2021-05-18 | Domain Therapeutics | Substituted tricyclic 1,4-benzodiazepinone derivatives as allosteric modulators of group II metabotropic glutamate receptors |
| CA3063288A1 (en) | 2017-05-12 | 2018-11-15 | Mavalon Therapeutics Limited | Substituted heterocyclic compounds as allosteric modulators of group ii metabotropic glutamate receptors |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA755418B (en) * | 1974-09-11 | 1977-06-29 | Hoffmann La Roche | Diazepine derivatives |
| US4280957A (en) * | 1974-09-11 | 1981-07-28 | Hoffmann-La Roche Inc. | Imidazodiazepines and processes therefor |
| CA1143728A (en) * | 1979-10-04 | 1983-03-29 | Max Gerecke | Imidazodiazepine derivatives |
| CA1174673A (en) * | 1981-02-27 | 1984-09-18 | Walter Hunkeler | Imidazodiazepines |
| DK151808C (da) * | 1982-11-16 | 1988-06-20 | Ferrosan As | Analogifremgangsmaade til fremstilling af oxadiazolylimidazo-oe1,4aa-benzodiazepinderivater |
| CS249146B2 (en) * | 1984-01-19 | 1987-03-12 | Hoffmann La Roche | Method of new imidazodiazepine's derivatives production |
| EP0202441B1 (en) * | 1985-05-17 | 1988-11-17 | A/S Ferrosan | Oxadiazolylimidazobenzodiazepines, process for their preparation and pharmaceutical compositions |
| DK174086D0 (da) * | 1986-04-16 | 1986-04-16 | Ferrosan As | Nye benzodiazepinderivater samt fremgangsmaade til fremstilling af samme |
| GB8720414D0 (en) * | 1987-08-28 | 1987-10-07 | Roussel Lab Ltd | Chemical compounds |
| CA1327572C (en) * | 1988-08-31 | 1994-03-08 | F. Hoffmann-La Roche Ag | Imidazodiazepine derivatives |
-
1988
- 1988-02-22 FI FI880814A patent/FI880814A7/fi not_active Application Discontinuation
- 1988-02-23 CA CA000559547A patent/CA1327571C/en not_active Expired - Fee Related
- 1988-03-03 IL IL85624A patent/IL85624A0/xx unknown
- 1988-03-03 NZ NZ223736A patent/NZ223736A/en unknown
- 1988-03-03 US US07/163,441 patent/US4863920A/en not_active Expired - Fee Related
- 1988-03-04 AU AU12710/88A patent/AU604300B2/en not_active Ceased
- 1988-03-07 HU HU881085A patent/HU201763B/hu not_active IP Right Cessation
- 1988-03-07 MC MC881954A patent/MC1918A1/xx unknown
- 1988-03-09 PT PT86925A patent/PT86925B/pt not_active IP Right Cessation
- 1988-03-09 DK DK127288A patent/DK127288A/da not_active Application Discontinuation
- 1988-03-09 DE DE8888103739T patent/DE3872559D1/de not_active Expired - Lifetime
- 1988-03-09 EP EP88103739A patent/EP0285837B1/de not_active Expired - Lifetime
- 1988-03-09 YU YU00479/88A patent/YU47988A/xx unknown
- 1988-03-09 ES ES88103739T patent/ES2051781T3/es not_active Expired - Lifetime
- 1988-03-09 KR KR1019880002420A patent/KR880011159A/ko not_active Withdrawn
- 1988-03-09 NO NO881054A patent/NO167027C/no unknown
-
1992
- 1992-10-08 GR GR920402228T patent/GR3005909T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO881054D0 (no) | 1988-03-09 |
| CA1327571C (en) | 1994-03-08 |
| AU1271088A (en) | 1988-09-15 |
| DK127288A (da) | 1988-09-11 |
| HUT47282A (en) | 1989-02-28 |
| YU47988A (en) | 1991-04-30 |
| FI880814A0 (fi) | 1988-02-22 |
| KR880011159A (ko) | 1988-10-26 |
| EP0285837B1 (de) | 1992-07-08 |
| ES2051781T3 (es) | 1994-07-01 |
| PT86925B (pt) | 1992-05-29 |
| FI880814A7 (fi) | 1988-09-11 |
| NO167027C (no) | 1991-09-25 |
| NO881054L (no) | 1988-09-12 |
| PT86925A (pt) | 1988-04-01 |
| MC1918A1 (fr) | 1989-04-06 |
| AU604300B2 (en) | 1990-12-13 |
| EP0285837A1 (de) | 1988-10-12 |
| GR3005909T3 (enEXAMPLES) | 1993-06-07 |
| IL85624A0 (en) | 1988-08-31 |
| NZ223736A (en) | 1992-01-29 |
| NO167027B (no) | 1991-06-17 |
| US4863920A (en) | 1989-09-05 |
| DK127288D0 (da) | 1988-03-09 |
| DE3872559D1 (de) | 1992-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1490344B1 (en) | Anxiolytic agents with reduced sedative and ataxic side effects | |
| CZ185092A3 (en) | Imidazodiazepines | |
| DE2540522A1 (de) | Diazepin-derivate | |
| HU189719B (en) | Process for preparing imidazo-benzodiazepine derivatives | |
| EP0377238A1 (en) | New annelated indolo (3,2-c)-lactams | |
| HU201763B (en) | Process for producing imidazodiazepine derivatives and pharmaceutical compositions comprising such compounds | |
| US4192803A (en) | 5H-Pyrrolo[2,1-c][1,4]benzodiazepine derivatives | |
| NO126325B (enEXAMPLES) | ||
| US5317018A (en) | Benzodiazepines and compositions for treating anxiety and panic disorders, and idiopathic and psychomotor epilepsy | |
| CA1083146A (en) | Process for the preparation of new benzodiazepine derivatives | |
| EP0222703A1 (de) | Hexahydro-[1]-benzo-(pyrano und thiopyrano)-[4,3-c]pyridine | |
| HU203889B (en) | Process for producing heterocyclic lactame derivatives and pharmaceutical compositions containing them as active components | |
| EP0072029B1 (de) | Triazolobenzazepine, Verfahren und Zwischenprodukte zu deren Herstellung und diese enthaltende Arzneimittel | |
| HU202531B (en) | Process for producing imidazodiazepine derivatives and pharmaceutical compositions comprising such compounds | |
| US4482714A (en) | Pyrazino[2',3'-3,4]pyrido[1,2-a]indole derivatives | |
| US4515949A (en) | [2-(1H-indol-1-yl)ethyl]-2-piperazine and pyrido[1,2-a]indol-9-one as intermediates for pyrazino(2,3-3,4)pyrido(1,2-a) indoles which are useful for treating hypertension in mammals | |
| US3996230A (en) | 1-Piperazino-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepines | |
| JPS6249273B2 (enEXAMPLES) | ||
| US4016165A (en) | Triazino benzodiazepines | |
| US3892763A (en) | 1-Propynylaminomethyl-6-phenyl-4H-s-triazolo{8 4,3-a{9 {8 1,4{9 benzodiazepines | |
| HU179948B (en) | Process for preparing new piperazino- and hexahydroazepino/1,2-a/-pyrrolo/2,1-c/1,4-benzodiazepine derivatives and pharmaceutical compositions containing such compounds | |
| US3294817A (en) | Octahydroindolobenzazepines and compounds intermediate thereto | |
| EP0276833A2 (en) | Dipyrazoles useful as bronchodilators | |
| US4409390A (en) | Pyrrolo[3,4-D][2]Benzazepines | |
| HU188071B (en) | Process for producing pyrrolo-benzodiazepine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HMM4 | Cancellation of final prot. due to non-payment of fee |