NO843376L - Benzodiazepinderivater - Google Patents

Benzodiazepinderivater

Info

Publication number: NO843376L
Authority: NO; Norway
Prior art keywords: benzodiazepine; chlorophenyl; imidazo; formula; methylene chloride
Prior art date: 1983-08-25

Application number

NO843376A

Other languages

English (en)

Norwegian (no)

Inventor

Rodney Ian Fryer

Armin Walser

Original Assignee

Hoffmann La Roche

Priority date (The priority date 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 date listed.)

1983-08-25

Filing date

1984-08-23

Publication date

1985-02-26

1984-08-23 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1985-02-26 Publication of NO843376L publication Critical patent/NO843376L/no

Links

229940049706 benzodiazepine Drugs 0.000 title description 10
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims description 133
-1 amino compound Chemical class 0.000 claims description 53
VUMCYGBPHCVIAY-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxamide Chemical compound NC(=O)C1=NNc2ccccc2C=C1 VUMCYGBPHCVIAY-UHFFFAOYSA-N 0.000 claims description 52
BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 51
239000001257 hydrogen Substances 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 28
238000000034 method Methods 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
239000007858 starting material Substances 0.000 claims description 13
150000002431 hydrogen Chemical class 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
150000008064 anhydrides Chemical class 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
125000001589 carboacyl group Chemical group 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
239000011737 fluorine Substances 0.000 claims description 6
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
KLNFAMGHSZQYHR-UHFFFAOYSA-N imidazo[4,5-i][1,2]benzodiazepine Chemical class C1=CC=NN=C2C3=NC=NC3=CC=C21 KLNFAMGHSZQYHR-UHFFFAOYSA-N 0.000 claims description 4
238000012546 transfer Methods 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 372
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 214
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 207
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 120
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 112
239000000243 solution Substances 0.000 description 105
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
239000013078 crystal Substances 0.000 description 73
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 70
239000000203 mixture Substances 0.000 description 66
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 56
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
238000006243 chemical reaction Methods 0.000 description 47
239000002904 solvent Substances 0.000 description 44
239000000047 product Substances 0.000 description 41
238000002425 crystallisation Methods 0.000 description 39
230000008025 crystallization Effects 0.000 description 39
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
125000004494 ethyl ester group Chemical group 0.000 description 31
238000003756 stirring Methods 0.000 description 30
229960000583 acetic acid Drugs 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 28
229910021529 ammonia Inorganic materials 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
239000012074 organic phase Substances 0.000 description 24
239000000706 filtrate Substances 0.000 description 23
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 22
238000010992 reflux Methods 0.000 description 21
239000000538 analytical sample Substances 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 19
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
LJGKKJWPDGDDEH-UHFFFAOYSA-N ethyl 1H-1,2-benzodiazepine-3-carboxylate Chemical compound C(C)OC(=O)C1=NNC2=C(C=C1)C=CC=C2 LJGKKJWPDGDDEH-UHFFFAOYSA-N 0.000 description 18
238000001953 recrystallisation Methods 0.000 description 18
239000012362 glacial acetic acid Substances 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
238000004458 analytical method Methods 0.000 description 16
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 16
239000002253 acid Substances 0.000 description 15
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
238000001816 cooling Methods 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 13
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
239000007868 Raney catalyst Substances 0.000 description 12
229910000564 Raney nickel Inorganic materials 0.000 description 12
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 12
150000001450 anions Chemical class 0.000 description 12
239000000155 melt Substances 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 12
229910000029 sodium carbonate Inorganic materials 0.000 description 11
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 10
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 10
238000001914 filtration Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
241000699670 Mus sp. Species 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
235000019270 ammonium chloride Nutrition 0.000 description 9
239000002585 base Substances 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
239000003153 chemical reaction reagent Substances 0.000 description 9
238000012360 testing method Methods 0.000 description 9
ONOBXDPYDHTSBQ-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-diazepine Chemical compound C1CC=CCNN1 ONOBXDPYDHTSBQ-UHFFFAOYSA-N 0.000 description 8
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
229910052783 alkali metal Inorganic materials 0.000 description 8
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
238000010438 heat treatment Methods 0.000 description 8
235000010288 sodium nitrite Nutrition 0.000 description 8
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
230000000949 anxiolytic effect Effects 0.000 description 7
239000002775 capsule Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000003480 eluent Substances 0.000 description 7
239000005457 ice water Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
239000000523 sample Substances 0.000 description 7
239000003826 tablet Substances 0.000 description 7
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 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
229910000831 Steel Inorganic materials 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
150000002170 ethers Chemical class 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
150000002430 hydrocarbons Chemical group 0.000 description 6
239000012071 phase Substances 0.000 description 6
238000003825 pressing Methods 0.000 description 6
239000010959 steel Substances 0.000 description 6
TWMOGFVGTHATIV-UHFFFAOYSA-N 2-(chloromethyl)-4-(2-chlorophenyl)-3-oxidoquinazolin-3-ium Chemical compound [O-][N+]1=C(CCl)N=C2C=CC=CC2=C1C1=CC=CC=C1Cl TWMOGFVGTHATIV-UHFFFAOYSA-N 0.000 description 5
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
238000009835 boiling Methods 0.000 description 5
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000012467 final product Substances 0.000 description 5
229930195733 hydrocarbon Natural products 0.000 description 5
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 5
238000007034 nitrosation reaction Methods 0.000 description 5
239000003921 oil Substances 0.000 description 5
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
238000005406 washing Methods 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 4
150000001204 N-oxides Chemical class 0.000 description 4
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
150000003973 alkyl amines Chemical class 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000011065 in-situ storage Methods 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
239000000463 material Substances 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
239000001632 sodium acetate Substances 0.000 description 4
235000017281 sodium acetate Nutrition 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
238000011282 treatment Methods 0.000 description 4
229910052720 vanadium Inorganic materials 0.000 description 4
HIRDYLVKLLGUTQ-UHFFFAOYSA-N (2-amino-4-chlorophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1Cl HIRDYLVKLLGUTQ-UHFFFAOYSA-N 0.000 description 3
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 3
QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 3
ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 description 3
HHEYPEZKVASXFW-UHFFFAOYSA-N 5-(2-bromophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound BrC1=CC=CC=C1C1=NCC(=O)NC2=CC=CC=C12 HHEYPEZKVASXFW-UHFFFAOYSA-N 0.000 description 3
DXAIBZTWPCDCFJ-UHFFFAOYSA-N 5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound ClC1=CC=CC=C1C1=NCC(=O)NC2=CC=CC=C12 DXAIBZTWPCDCFJ-UHFFFAOYSA-N 0.000 description 3
IFCPYKRHAGUXOQ-UHFFFAOYSA-N 6-fluoro-3-(2-fluorophenyl)-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC(F)=CC=C2C=1C1=CC=CC=C1F IFCPYKRHAGUXOQ-UHFFFAOYSA-N 0.000 description 3
SVDYIODNHANAPQ-UHFFFAOYSA-N 6-fluoro-3-(2-fluorophenyl)-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(F)=CC=C2C=1C1=CC=CC=C1F SVDYIODNHANAPQ-UHFFFAOYSA-N 0.000 description 3
RRSKLMXUNFCGKD-UHFFFAOYSA-N 7-chloro-2-(chloromethyl)-4-(2-chlorophenyl)-3-oxidoquinazolin-3-ium Chemical compound [O-][N+]1=C(CCl)N=C2C=C(Cl)C=CC2=C1C1=CC=CC=C1Cl RRSKLMXUNFCGKD-UHFFFAOYSA-N 0.000 description 3
BYVWCFBXIBXYES-UHFFFAOYSA-N 8-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C=1C(F)=CC=C2C=1NC(=O)CN=C2C1=CC=CC=C1F BYVWCFBXIBXYES-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
206010010904 Convulsion Diseases 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 3
NASVANHOMILYPU-UHFFFAOYSA-N [3-(2-chlorophenyl)-6-fluoro-1h-indol-2-yl]methanamine;hydrochloride Chemical compound Cl.NCC=1NC2=CC(F)=CC=C2C=1C1=CC=CC=C1Cl NASVANHOMILYPU-UHFFFAOYSA-N 0.000 description 3
KWHXHQUWPIEXNC-UHFFFAOYSA-N [O-][N+]1=C(C2=CC=CC=C2NC(=O)C1)C1=C(Cl)C=CC=C1 Chemical compound [O-][N+]1=C(C2=CC=CC=C2NC(=O)C1)C1=C(Cl)C=CC=C1 KWHXHQUWPIEXNC-UHFFFAOYSA-N 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
125000004423 acyloxy group Chemical group 0.000 description 3
238000007098 aminolysis reaction Methods 0.000 description 3
238000010171 animal model Methods 0.000 description 3
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
230000036461 convulsion Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
MTRGCJCFSCFWDX-UHFFFAOYSA-N dimethyl 2-[1-[5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-ylidene]ethyl]propanedioate Chemical compound COC(=O)C(C(C)=C1NC2=C(C(=NC1)C1=C(C=CC=C1)Cl)C=CC=C2)C(=O)OC MTRGCJCFSCFWDX-UHFFFAOYSA-N 0.000 description 3
229940079593 drug Drugs 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
229910000378 hydroxylammonium sulfate Inorganic materials 0.000 description 3
OJYWZAXHVNKQPF-UHFFFAOYSA-N methyl 6-fluoro-3-(2-fluorophenyl)-1H-indole-2-carboxylate Chemical compound COC(=O)C=1NC2=CC(=CC=C2C=1C1=C(C=CC=C1)F)F OJYWZAXHVNKQPF-UHFFFAOYSA-N 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
230000009935 nitrosation Effects 0.000 description 3
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150000002367 halogens Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
231100000636 lethal dose Toxicity 0.000 description 1
239000007788 liquid Substances 0.000 description 1
AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
XQELSYTZKFGZEL-UHFFFAOYSA-N methyl 2-[(2-fluorophenyl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=CC=C1F XQELSYTZKFGZEL-UHFFFAOYSA-N 0.000 description 1
GFUACTZSLJVREI-UHFFFAOYSA-N methyl 2-[5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2-yl]-2-hydroxyiminoacetate Chemical compound COC(C(C1=NC2=C(C(=NC1)C1=C(C=CC=C1)Cl)C=CC=C2)=NO)=O GFUACTZSLJVREI-UHFFFAOYSA-N 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical class COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
BLLFVUPNHCTMSV-UHFFFAOYSA-N methyl nitrite Chemical compound CON=O BLLFVUPNHCTMSV-UHFFFAOYSA-N 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
229940035363 muscle relaxants Drugs 0.000 description 1
230000036225 muscular coordination Effects 0.000 description 1
239000003158 myorelaxant agent Substances 0.000 description 1
MUMVIYLVHVCYGI-UHFFFAOYSA-N n,n,n',n',n",n"-hexamethylmethanetriamine Chemical compound CN(C)C(N(C)C)N(C)C MUMVIYLVHVCYGI-UHFFFAOYSA-N 0.000 description 1
GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000001272 nitrous oxide Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000865 phosphorylative effect Effects 0.000 description 1
239000010773 plant oil Substances 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000002040 relaxant effect Effects 0.000 description 1
239000005060 rubber Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
229910000077 silane Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
150000003511 tertiary amides Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
- C07D239/76—N-oxides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Anesthesiology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

NO843376A 1983-08-25 1984-08-23 Benzodiazepinderivater NO843376L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US52619483A	1983-08-25	1983-08-25

Publications (1)

Publication Number	Publication Date
NO843376L true NO843376L (no)	1985-02-26

Family

ID=24096318

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO843376A NO843376L (no)	1983-08-25	1984-08-23	Benzodiazepinderivater

Country Status (16)

Country	Link
EP (1)	EP0135770A3 (da)
JP (1)	JPS6067480A (da)
KR (1)	KR850001756A (da)
AU (1)	AU3237984A (da)
DK (1)	DK406384A (da)
ES (2)	ES535392A0 (da)
FI (1)	FI843356A7 (da)
GR (1)	GR80197B (da)
HU (1)	HU193588B (da)
IL (1)	IL72757A0 (da)
MC (1)	MC1616A1 (da)
NO (1)	NO843376L (da)
NZ (1)	NZ209316A (da)
PH (1)	PH20029A (da)
PT (1)	PT79131B (da)
ZA (1)	ZA845757B (da)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2635776B1 (fr) *	1988-09-01	1993-06-11	Rhone Poulenc Agrochimie	Derives amides, procede pour leur fabrication et compositions fongicides les contenant
IL91418A (en) *	1988-09-01	1997-11-20	Rhone Poulenc Agrochimie	(hetero) cyclic amide derivatives, process for their preparation and fungicidal compositions containing them
US5317018A (en) *	1992-06-09	1994-05-31	Armin Walser	Benzodiazepines and compositions for treating anxiety and panic disorders, and idiopathic and psychomotor epilepsy
TW234123B (da) *	1992-12-16	1994-11-11	Takeda Pharm Industry Co Ltd
US6063921A (en) *	1997-11-20	2000-05-16	Pharm-Eco Laboratories, Inc.	Synthesis of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines
US8119629B2 (en)	2007-10-03	2012-02-21	Bristol-Meyers Squibb Company	Carboxamide GABAA α2 modulators
AU2017313753B2 (en)	2016-08-16	2022-01-27	The Trustees Of Columbia University In The City Of New York	GABA(A) receptor modulators and methods to control airway hyperresponsiveness and inflammation in asthma

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA755418B (en) *	1974-09-11	1977-06-29	Hoffmann La Roche	Diazepine derivatives
AT361486B (de) *	1975-08-07	1981-03-10	Hoffmann La Roche	Verfahren zur herstellung von neuen imidazo(1,5 -a) (1,4)diazepinverbindungen, ihren salzen und optisch aktiven formen
US4125726A (en) *	1977-03-11	1978-11-14	Hoffmann-La Roche Inc.	Imidazo[1,5-a][1,4]benzodiazepines
DK151808C (da) *	1982-11-16	1988-06-20	Ferrosan As	Analogifremgangsmaade til fremstilling af oxadiazolylimidazo-oe1,4aa-benzodiazepinderivater

1984
- 1984-07-25 ZA ZA845757A patent/ZA845757B/xx unknown
- 1984-08-13 EP EP84109639A patent/EP0135770A3/de not_active Withdrawn
- 1984-08-23 NO NO843376A patent/NO843376L/no unknown
- 1984-08-23 NZ NZ209316A patent/NZ209316A/en unknown
- 1984-08-23 IL IL72757A patent/IL72757A0/xx unknown
- 1984-08-23 MC MC841721A patent/MC1616A1/fr unknown
- 1984-08-23 GR GR80197A patent/GR80197B/el unknown
- 1984-08-24 PT PT79131A patent/PT79131B/pt unknown
- 1984-08-24 ES ES535392A patent/ES535392A0/es active Granted
- 1984-08-24 DK DK406384A patent/DK406384A/da not_active Application Discontinuation
- 1984-08-24 AU AU32379/84A patent/AU3237984A/en not_active Abandoned
- 1984-08-24 JP JP59175328A patent/JPS6067480A/ja active Pending
- 1984-08-24 KR KR1019840005134A patent/KR850001756A/ko not_active Withdrawn
- 1984-08-24 HU HU843179A patent/HU193588B/hu unknown
- 1984-08-24 PH PH31144A patent/PH20029A/en unknown
- 1984-08-24 FI FI843356A patent/FI843356A7/fi not_active Application Discontinuation
1985
- 1985-05-31 ES ES543717A patent/ES8603433A1/es not_active Expired

Also Published As

Publication number	Publication date
PT79131A (en)	1984-09-01
FI843356A7 (fi)	1985-02-26
NZ209316A (en)	1987-04-30
IL72757A0 (en)	1984-11-30
FI843356A0 (fi)	1984-08-24
KR850001756A (ko)	1985-04-01
HU193588B (en)	1987-10-28
GR80197B (en)	1985-01-03
ES8602700A1 (es)	1985-12-01
ES543717A0 (es)	1986-01-01
ZA845757B (en)	1985-04-24
EP0135770A2 (de)	1985-04-03
EP0135770A3 (de)	1988-01-13
ES8603433A1 (es)	1986-01-01
PH20029A (en)	1986-09-04
DK406384A (da)	1985-02-26
MC1616A1 (fr)	1985-07-18
ES535392A0 (es)	1985-12-01
AU3237984A (en)	1985-02-28
JPS6067480A (ja)	1985-04-17
HUT34978A (en)	1985-05-28
DK406384D0 (da)	1984-08-24
PT79131B (en)	1986-11-14

Publication	Publication Date	Title
US5811422A (en)	1998-09-22	Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors
JP2002533465A (ja)	2002-10-08	Ｘａ因子阻害剤としての窒素を含む複素二環類
CA1076572A (en)	1980-04-29	Diazepine derivatives
TW201102375A (en)	2011-01-16	Hedgehog pathway antagonists and therapeutic applications thereof
SE449098B (sv)	1987-04-06	Fenyl-/2-(5-hydroxi-1-imidazolyl)fenyl/-metanonderivat till anvendning som mellanprodukter for framstellning av imidazo/1,5-a//1,4/bensodiazepinderivat
CA1090333A (en)	1980-11-25	Process for the manufacture of diazepine derivatives
Fryer et al.	1964	Quinazolines and 1, 4‐benzodiazepines XVII. Synthesis of 1, 3‐dihydro‐5‐pyridyl‐2H‐1, 4‐benzodiazepine derivatives
US3784542A (en)	1974-01-08	Benzodiazepin-2-ones
HU193588B (en)	1987-10-28	Process for preparing imidazo benzodiazepine derivatives
NO300418B1 (no)	1997-05-26	Nye perhydroisoindolderivater
US6140320A (en)	2000-10-31	5,5-disubstituted-1,5-dihydro-4,1-benzoxazepin-2 (3H)-ones useful as HIV reverse transcriptase inhibitors
US4464300A (en)	1984-08-07	Triazolo benzazepines
NO148814B (no)	1983-09-12	Analogifremgangsmaate ved fremstilling av terapeutisk aktive diazepinderivater.
US3732211A (en)	1973-05-08	1-acyloxyether-1,4-benzodiazepin-2-ones and methods for their preparation
NO157376B (no)	1987-11-30	Analogifremgangsmaate ved fremstilling av terapeutisk aktive 2-fenylacylaminomethyl-1,4-benzodiazepiner.
US3513158A (en)	1970-05-19	Process for preparing 5-aryl benzodiazepines and intermediates
US3329701A (en)	1967-07-04	Cyanobenzophenones
NO128328B (da)	1973-10-29
Chou et al.	1997	METHOXYPYRIDINE: A KEY INTERMEDIATE FOR OMEPRAZOLE
US3772305A (en)	1973-11-13	3-amino-3-carbalkoxy-4-hydroxy-2-oxo-4-phenyl-1,2,3,4-tetrahydroquinolines
KR800001087B1 (ko)	1980-10-06	디아제핀 유도체의 제조방법
US3886214A (en)	1975-05-27	Benzodiazepin-2-ones and processes for the preparation thereof
Fryer et al.	1977	The synthesis of 2‐phenyl‐5H‐imidazo [2, 1‐a][2, 4] benzodiazepines
US4073784A (en)	1978-02-14	Certain as-triazino 4,3-a! 1,4!benzodiazepine-1,2-dione compounds
US3632573A (en)	1972-01-04	Method for producing benzodiazepine derivatives