DE2221790A1 - Neue 6-Phenyl-s-triazolobenzodiazepinderivate und Verfahren zur Herstellung derselben - Google Patents
Neue 6-Phenyl-s-triazolobenzodiazepinderivate und Verfahren zur Herstellung derselbenInfo
- Publication number
- DE2221790A1 DE2221790A1 DE19722221790 DE2221790A DE2221790A1 DE 2221790 A1 DE2221790 A1 DE 2221790A1 DE 19722221790 DE19722221790 DE 19722221790 DE 2221790 A DE2221790 A DE 2221790A DE 2221790 A1 DE2221790 A1 DE 2221790A1
- Authority
- DE
- Germany
- Prior art keywords
- phenyl
- methyl
- compound
- chloro
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 88
- -1 nitromethyl Chemical group 0.000 claims description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 49
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 20
- 229940049706 benzodiazepine Drugs 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
- 239000007858 starting material Substances 0.000 claims description 17
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 claims description 15
- BAVAZRNEAWBRLO-UHFFFAOYSA-N 1,2-benzodiazepin-4-one Chemical compound O=C1C=NN=C2C=CC=CC2=C1 BAVAZRNEAWBRLO-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 150000004965 peroxy acids Chemical class 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 2
- MTNWQRGOHOXCFV-UHFFFAOYSA-N 7-chloro-2-methoxy-4-oxido-5-phenyl-3h-1,4-benzodiazepin-4-ium Chemical compound [O-][N+]=1CC(OC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 MTNWQRGOHOXCFV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 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
- AAIUDRBUXYUHNQ-UHFFFAOYSA-N 4-hydroxy-1,4-benzodiazepine Chemical compound ON1C=CN=C2C=CC=CC2=C1 AAIUDRBUXYUHNQ-UHFFFAOYSA-N 0.000 claims 1
- FSQGKKLKVFCXJV-UHFFFAOYSA-N 8-chloro-1-methyl-6-phenyl-5,6-dihydro-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-one Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2C(=O)NC1C1=CC=CC=C1 FSQGKKLKVFCXJV-UHFFFAOYSA-N 0.000 claims 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- PBDYKLIQMZIDKS-UHFFFAOYSA-N N1=NC=C(CC2=C1C=CC=C2)O Chemical compound N1=NC=C(CC2=C1C=CC=C2)O PBDYKLIQMZIDKS-UHFFFAOYSA-N 0.000 claims 1
- 229940125890 compound Ia Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 229940093499 ethyl acetate Drugs 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- 238000000354 decomposition reaction Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 4
- 239000000932 sedative agent Substances 0.000 description 4
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 230000002921 anti-spasmodic effect Effects 0.000 description 3
- FCCCRBDJBTVFSJ-UHFFFAOYSA-N butanehydrazide Chemical compound CCCC(=O)NN FCCCRBDJBTVFSJ-UHFFFAOYSA-N 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 3
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 3
- NJPPVKZQTLUDBO-UHFFFAOYSA-N novaluron Chemical compound C1=C(Cl)C(OC(F)(F)C(OC(F)(F)F)F)=CC=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F NJPPVKZQTLUDBO-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000001624 sedative effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- GOOCRIHPADOQAS-ZNUXJMJHSA-N (4ar,5as,8ar,13as,15as,15br)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2h-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinoline-14-one;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1.O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 GOOCRIHPADOQAS-ZNUXJMJHSA-N 0.000 description 2
- ROFVGYAMRSGUSQ-UHFFFAOYSA-N 1-(2-bromoethyl)piperazine;hydrobromide Chemical compound Br.BrCCN1CCNCC1 ROFVGYAMRSGUSQ-UHFFFAOYSA-N 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- XCXMEYSBBHIZEF-UHFFFAOYSA-N 4-(2-benzoyl-4-chlorophenyl)-5-methyl-1,2,4-triazole-3-carbaldehyde Chemical compound CC1=NN=C(C=O)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 XCXMEYSBBHIZEF-UHFFFAOYSA-N 0.000 description 2
- ZGTMQRKFGRSXCF-UHFFFAOYSA-N 4-(2-benzoylphenyl)-1,2,4-triazole-3-carbaldehyde Chemical class C(C1=CC=CC=C1)(=O)C1=C(C=CC=C1)N1C(=NN=C1)C=O ZGTMQRKFGRSXCF-UHFFFAOYSA-N 0.000 description 2
- TYCLCPMBFYXTIU-UHFFFAOYSA-N 5-oxido-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-5-ium Chemical class C1=NN=C2N1C1=C(C=[N+](C2)[O-])C=CC=C1 TYCLCPMBFYXTIU-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
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- 239000003674 animal food additive Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
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- 238000010438 heat treatment Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N hexane carboxylic acid Natural products CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000000147 hypnotic effect Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229940125723 sedative agent Drugs 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 229960000412 strychnine sulfate Drugs 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- KYTREVLPRJOBEM-UHFFFAOYSA-N triazolo[4,5-i][1,2]benzodiazepine Chemical class C1=CC2=CC=CN=NC2=C2C1=NN=N2 KYTREVLPRJOBEM-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
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- HYYFATVGUNWPOG-UHFFFAOYSA-N phenyl-[2-(1,2,4-triazol-4-yl)phenyl]methanone Chemical compound C=1C=CC=C(N2C=NN=C2)C=1C(=O)C1=CC=CC=C1 HYYFATVGUNWPOG-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14241871A | 1971-05-11 | 1971-05-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2221790A1 true DE2221790A1 (de) | 1972-11-23 |
Family
ID=22499766
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19722221790 Pending DE2221790A1 (de) | 1971-05-11 | 1972-05-04 | Neue 6-Phenyl-s-triazolobenzodiazepinderivate und Verfahren zur Herstellung derselben |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US3681343A (enExample) |
| AU (1) | AU472686B2 (enExample) |
| BE (1) | BE783273A (enExample) |
| CH (3) | CH582180A5 (enExample) |
| DE (1) | DE2221790A1 (enExample) |
| FR (1) | FR2137713B1 (enExample) |
| GB (2) | GB1380880A (enExample) |
| NL (1) | NL7206302A (enExample) |
| ZA (1) | ZA722560B (enExample) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2156472A1 (de) | 1970-11-23 | 1972-05-31 | Ciba-Geigy Ag, Basel (Schweiz) | Verfahren zur Herstellung von neuen Diazepinderivaten |
| JPS4932874B1 (enExample) * | 1970-12-11 | 1974-09-03 | ||
| CH545302A (de) * | 1971-04-08 | 1974-01-13 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Triazolo-benzodiazepinderivaten |
| US3946032A (en) * | 1971-04-08 | 1976-03-23 | Ciba-Geigy Corporation | Acetal derivatives of 6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde |
| US4902794A (en) * | 1971-04-28 | 1990-02-20 | The Upjohn Company | Triazolo-benzodiazepines |
| US4250094A (en) * | 1971-04-28 | 1981-02-10 | The Upjohn Company | 1-(Aminoalkyl) substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines |
| DE2308280A1 (de) * | 1971-11-15 | 1973-09-06 | Ciba Geigy Ag | Verfahren zur herstellung von neuen diazepinderivaten |
| US3886174A (en) * | 1971-11-22 | 1975-05-27 | Upjohn Co | 1-Substituted-6-phenyl-4H-s-triazolo{8 4,3-a{9 {8 1,4{9 benzodiazepines |
| CH567031A5 (enExample) * | 1972-05-18 | 1975-09-30 | Ciba Geigy Ag | |
| US3879406A (en) * | 1972-07-13 | 1975-04-22 | Hoffmann La Roche | Preparation of triazolobenzodiazepines |
| IE38931B1 (en) * | 1973-03-09 | 1978-07-05 | Lipha | Triazolobenzodiazepines |
| IE41197B1 (en) | 1973-05-29 | 1979-11-07 | Squibb & Sons Inc | 4h-s-triazolo (4,3-a)(1,5)benzodiazepin-5-ones |
| US4213982A (en) | 1973-05-29 | 1980-07-22 | E. R. Squibb & Sons, Inc. | Novel 4H-S-triazolo[4,3-A] [1,5]benzodiazepin-5-ones |
| AT338799B (de) | 1974-03-02 | 1977-09-12 | Boehringer Sohn Ingelheim | Verfahren zur herstellung neuer substituierter 6-aryl-4h-s-triazolo-(3,4c)-thieno-(2,3e)-1,4-diazepine und ihrer salze |
| JPS5747914B2 (enExample) * | 1974-04-12 | 1982-10-13 | ||
| US3910944A (en) * | 1974-11-20 | 1975-10-07 | Upjohn Co | Spiro(cyclopropane-1,4{40 -(4H)-s-triazolo-(4,3-a)(1,4)benzodiazepines) |
| US4044016A (en) * | 1975-01-13 | 1977-08-23 | Hoffmann-La Roche Inc. | Preparation of triazolo benzodiazepines and novel compounds |
| US4018788A (en) * | 1975-06-16 | 1977-04-19 | The Upjohn Company | 6-(O-Halophenyl)-1-methyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine |
| US4009175A (en) * | 1976-03-15 | 1977-02-22 | The Upjohn Company | 1-[(Aminooxy)-methyl]-6-substituted-4H-s-triazolo[4,3-a][1,4] benzodiazepines |
| US4226772A (en) * | 1976-03-15 | 1980-10-07 | The Upjohn Company | 1-[(Dialkylamino)methyl]-6-phenyl-4H-s-[4,3,-a][1,4]triazolobenzodiazepine N1 -oxide |
| US4415583A (en) * | 1980-03-27 | 1983-11-15 | The Upjohn Company | Process for inducing hypnosis |
| US4374842A (en) * | 1980-04-18 | 1983-02-22 | Shionogi & Co., Ltd. | 4,1-Benzoxazepines and compositions |
| US4479959A (en) * | 1981-01-29 | 1984-10-30 | The Upjohn Company | Process for inducing hypnosis |
| US4444781A (en) * | 1981-04-06 | 1984-04-24 | The Upjohn Company | Process for inducing hypnosis |
| HUE031073T2 (en) | 2010-05-14 | 2017-06-28 | Dana Farber Cancer Inst Inc | Thieno triazolo-diazepine compounds for the treatment of neoplasia |
| CA2799403C (en) | 2010-05-14 | 2020-01-21 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating leukemia |
| AU2015201727B2 (en) * | 2010-05-14 | 2018-03-08 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating neoplasia, inflammatory disease and other disorders |
| WO2011143657A1 (en) | 2010-05-14 | 2011-11-17 | Dana-Farber Cancer Institute, Inc. | Male contraceptive compositions and methods of use |
| WO2012075456A1 (en) | 2010-12-02 | 2012-06-07 | Constellation Pharmaceuticals | Bromodomain inhibitors and uses thereof |
| AR084070A1 (es) | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| EP2705039B1 (en) | 2011-05-04 | 2017-07-26 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| EP2721031B1 (en) | 2011-06-17 | 2016-01-20 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| TWI602820B (zh) | 2012-06-06 | 2017-10-21 | 星宿藥物公司 | 溴域抑制劑及其用途 |
| EP2864336B1 (en) | 2012-06-06 | 2016-11-23 | Constellation Pharmaceuticals, Inc. | Benzo[b]isoxazoloazepine bromodomain inhibitors and uses thereof |
| KR20160034379A (ko) | 2013-07-25 | 2016-03-29 | 다나-파버 캔서 인스티튜트 인크. | 전사 인자의 억제제 및 그의 용도 |
| RU2016122654A (ru) | 2013-11-08 | 2017-12-14 | Дана-Фарбер Кэнсер Инститьют, Инк. | Комбинированная терапия злокачественной опухоли с использованием ингибиторов бромодоменового и экстратерминального (вет) белка |
| US10793571B2 (en) | 2014-01-31 | 2020-10-06 | Dana-Farber Cancer Institute, Inc. | Uses of diazepane derivatives |
| US10150756B2 (en) | 2014-01-31 | 2018-12-11 | Dana-Farber Cancer Institute, Inc. | Diaminopyrimidine benzenesulfone derivatives and uses thereof |
| CA2940472A1 (en) | 2014-02-28 | 2015-09-03 | Tensha Therapeutics, Inc. | Treatment of conditions associated with hyperinsulinaemia |
| US9969747B2 (en) | 2014-06-20 | 2018-05-15 | Constellation Pharmaceuticals, Inc. | Crystalline forms of 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[C]isoxazolo[4,5-e]azepin-4-yl)acetamide |
| RU2017104897A (ru) | 2014-08-08 | 2018-09-10 | Дана-Фарбер Кэнсер Инститьют, Инк. | Производные диазепана и их применения |
| EP3177147A4 (en) | 2014-08-08 | 2018-01-24 | Dana-Farber Cancer Institute, Inc. | Dihydropteridinone derivatives and uses thereof |
| EA033325B1 (ru) | 2014-10-27 | 2019-09-30 | Тэнша Терапеутикс, Инк. | Ингибиторы бромодомена |
| CA2986441A1 (en) | 2015-06-12 | 2016-12-15 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| KR20180051576A (ko) | 2015-09-11 | 2018-05-16 | 다나-파버 캔서 인스티튜트 인크. | 아세트아미드 티에노트리아졸로디아제핀 및 그의 용도 |
| CN108472300A (zh) | 2015-09-11 | 2018-08-31 | 达纳-法伯癌症研究所股份有限公司 | 氰基噻吩并三唑并二氮杂环庚三烯及其用途 |
| PE20181298A1 (es) | 2015-11-25 | 2018-08-07 | Dana Farber Cancer Inst Inc | Inhibidores de bromodominio bivalentes y usos de los mismos |
| CA3063288A1 (en) | 2017-05-12 | 2018-11-15 | Mavalon Therapeutics Limited | Substituted heterocyclic compounds as allosteric modulators of group ii metabotropic glutamate receptors |
| CA3167543A1 (en) | 2020-03-31 | 2021-10-07 | F. Hoffmann-La Roche Ag | Benzodiazepine derivatives as gaba a gamma1 pams |
| WO2023052312A1 (en) | 2021-09-29 | 2023-04-06 | F. Hoffmann-La Roche Ag | New benzodiazepine derivatives as gaba a gamma1 pam |
| US12344614B2 (en) | 2021-10-06 | 2025-07-01 | Hoffmann-La Roche Inc. | Benzodiazepine derivatives as GABA a GAMMA1 PAM |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH540247A (de) * | 1967-04-21 | 1973-09-28 | Ciba Geigy Ag | Verfahren zur Herstellung von heterocyclischen, Asthylendoppelbindungen enthaltenden Verbindungen |
| JPS4837280B1 (enExample) * | 1969-03-08 | 1973-11-09 | ||
| YU34997B (en) * | 1970-03-27 | 1980-06-30 | Hiroyuki Tawada | Process for preparing benzodiazepine derivatives |
-
1971
- 1971-05-11 US US142418A patent/US3681343A/en not_active Expired - Lifetime
-
1972
- 1972-04-12 GB GB5857273A patent/GB1380880A/en not_active Expired
- 1972-04-12 GB GB1691372A patent/GB1377435A/en not_active Expired
- 1972-04-17 ZA ZA722560A patent/ZA722560B/xx unknown
- 1972-04-27 AU AU41640/72A patent/AU472686B2/en not_active Expired
- 1972-05-04 DE DE19722221790 patent/DE2221790A1/de active Pending
- 1972-05-10 CH CH698872A patent/CH582180A5/xx not_active IP Right Cessation
- 1972-05-10 BE BE783273A patent/BE783273A/xx not_active IP Right Cessation
- 1972-05-10 CH CH1394375A patent/CH572485A5/xx not_active IP Right Cessation
- 1972-05-10 CH CH1394475A patent/CH573942A5/xx not_active IP Right Cessation
- 1972-05-10 FR FR7216686A patent/FR2137713B1/fr not_active Expired
- 1972-05-10 NL NL7206302A patent/NL7206302A/xx not_active Application Discontinuation
-
1973
- 1973-07-13 US US37909373 patent/USRE28505E/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2137713A1 (enExample) | 1972-12-29 |
| CH573942A5 (enExample) | 1976-03-31 |
| AU4164072A (en) | 1973-11-01 |
| BE783273A (fr) | 1972-11-10 |
| NL7206302A (enExample) | 1972-11-14 |
| CH582180A5 (enExample) | 1976-11-30 |
| GB1380880A (en) | 1975-01-15 |
| CH572485A5 (enExample) | 1976-02-13 |
| AU472686B2 (en) | 1976-06-03 |
| FR2137713B1 (enExample) | 1975-12-26 |
| US3681343A (en) | 1972-08-01 |
| ZA722560B (en) | 1973-02-28 |
| USRE28505E (en) | 1975-08-05 |
| GB1377435A (en) | 1974-12-18 |
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