JPS6157582A - 新規なベンゾジアゼピン類 - Google Patents
新規なベンゾジアゼピン類Info
- Publication number
- JPS6157582A JPS6157582A JP60184317A JP18431785A JPS6157582A JP S6157582 A JPS6157582 A JP S6157582A JP 60184317 A JP60184317 A JP 60184317A JP 18431785 A JP18431785 A JP 18431785A JP S6157582 A JPS6157582 A JP S6157582A
- Authority
- JP
- Japan
- Prior art keywords
- benzodiazepine
- formula
- spiro
- alkyl
- unsubstituted
- 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.)
- Granted
Links
- 229940049706 benzodiazepine Drugs 0.000 title claims abstract description 17
- 150000001557 benzodiazepines Chemical class 0.000 title claims abstract description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
- 201000010099 disease Diseases 0.000 claims abstract description 5
- 208000000044 Amnesia Diseases 0.000 claims abstract 2
- 208000031091 Amnestic disease Diseases 0.000 claims abstract 2
- 230000006986 amnesia Effects 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 7
- 230000006870 function Effects 0.000 claims description 7
- 230000029936 alkylation Effects 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 3
- 208000014644 Brain disease Diseases 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000007017 scission Effects 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- 125000003107 substituted aryl group Chemical group 0.000 claims 4
- 230000007087 memory ability Effects 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 12
- 238000000034 method Methods 0.000 abstract description 11
- 150000003839 salts Chemical class 0.000 abstract description 11
- 239000002253 acid Substances 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 3
- 208000018152 Cerebral disease Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 33
- 239000000243 solution Substances 0.000 description 28
- 239000002904 solvent Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 10
- -1 triethylamine Chemical class 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 239000007795 chemical reaction product Substances 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000005932 reductive alkylation reaction Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000003826 tablet Substances 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
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 3
- 150000003931 anilides Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 150000002148 esters Chemical group 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 241000411851 herbal medicine Species 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- UAPJXCZSNCQLMR-UHFFFAOYSA-N 4-amino-1-benzylpiperidin-1-ium-4-carboxylate Chemical compound C1CC(N)(C(O)=O)CCN1CC1=CC=CC=C1 UAPJXCZSNCQLMR-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RLUFBDIRFJGKLY-UHFFFAOYSA-N (2,3-dichlorophenyl)-phenylmethanone Chemical compound ClC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1Cl RLUFBDIRFJGKLY-UHFFFAOYSA-N 0.000 description 1
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- UMPFWXKTYANUAO-UHFFFAOYSA-N 1'-benzyl-7-chloro-1-methyl-5-phenylspiro[1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound O=C1N(C)C2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)=NC1(CC1)CCN1CC1=CC=CC=C1 UMPFWXKTYANUAO-UHFFFAOYSA-N 0.000 description 1
- YYULVXCZQOEUNU-UHFFFAOYSA-N 1'-benzyl-7-chloro-5-(3-iodophenyl)spiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1=C(C=2C=C(I)C=CC=2)C2=CC(Cl)=CC=C2NC(=O)C1(CC1)CCN1CC1=CC=CC=C1 YYULVXCZQOEUNU-UHFFFAOYSA-N 0.000 description 1
- HOIDHMTWECEBAF-UHFFFAOYSA-N 1'-benzyl-7-chloro-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2NC(=O)C1(CC1)CCN1CC1=CC=CC=C1 HOIDHMTWECEBAF-UHFFFAOYSA-N 0.000 description 1
- YEDCPLQQEWPAHI-UHFFFAOYSA-N 1'-benzyl-7-nitro-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1=C(C=2C=CC=CC=2)C2=CC([N+](=O)[O-])=CC=C2NC(=O)C1(CC1)CCN1CC1=CC=CC=C1 YEDCPLQQEWPAHI-UHFFFAOYSA-N 0.000 description 1
- UJPMYEOUBPIPHQ-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound CC(F)(F)F UJPMYEOUBPIPHQ-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- VXZBYIWNGKSFOJ-UHFFFAOYSA-N 2-[4-[5-(2,3-dihydro-1H-inden-2-ylamino)pyrazin-2-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC=1N=CC(=NC=1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 VXZBYIWNGKSFOJ-UHFFFAOYSA-N 0.000 description 1
- HEQOJEGTZCTHCF-UHFFFAOYSA-N 2-amino-1-phenylethanone Chemical compound NCC(=O)C1=CC=CC=C1 HEQOJEGTZCTHCF-UHFFFAOYSA-N 0.000 description 1
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 1
- QZEXGWULKNWLKE-UHFFFAOYSA-N 2-oxo-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-7-carbonitrile Chemical compound O=C1NC2=CC=C(C#N)C=C2C(C=2C=CC=CC=2)=NC11CCNCC1 QZEXGWULKNWLKE-UHFFFAOYSA-N 0.000 description 1
- GADHRNJYPITOQZ-UHFFFAOYSA-N 2-oxo-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-8-carbonitrile Chemical compound O=C1NC2=CC(C#N)=CC=C2C(C=2C=CC=CC=2)=NC11CCNCC1 GADHRNJYPITOQZ-UHFFFAOYSA-N 0.000 description 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- AWFJYFUBNSFVBE-UHFFFAOYSA-N 5-(2-phenylethyl)spiro[1H-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N=1C2(CCNCC2)C(=O)NC2=CC=CC=C2C=1CCC1=CC=CC=C1 AWFJYFUBNSFVBE-UHFFFAOYSA-N 0.000 description 1
- XOLYLZVISYAFKA-UHFFFAOYSA-N 5-benzyl-7-chlorospiro[1H-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1=C(CC=2C=CC=CC=2)C2=CC(Cl)=CC=C2NC(=O)C21CCNCC2 XOLYLZVISYAFKA-UHFFFAOYSA-N 0.000 description 1
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- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 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
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D471/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843431195 DE3431195A1 (de) | 1984-08-24 | 1984-08-24 | Neue benzodiazepine, verfahren zu ihrer herstellung sowie ihre verwendung |
| DE3431195.5 | 1984-08-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6157582A true JPS6157582A (ja) | 1986-03-24 |
| JPH0378868B2 JPH0378868B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-12-17 |
Family
ID=6243820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60184317A Granted JPS6157582A (ja) | 1984-08-24 | 1985-08-23 | 新規なベンゾジアゼピン類 |
Country Status (19)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4957915A (en) * | 1989-02-27 | 1990-09-18 | Biomeasure, Inc. | Benzodiazepine analogs |
| CA2160786A1 (en) * | 1993-05-14 | 1994-11-24 | James C. Marsters, Jr. | Ras farnesyl transferase inhibitors |
| CA2469879A1 (en) * | 2001-12-14 | 2003-06-26 | Merck & Co. Inc. | A novel sordarin derivative isolated from culture fermentations and functions as an antifungal agent |
| EP1591120A4 (en) * | 2003-01-28 | 2009-06-10 | Takeda Chemical Industries Ltd | RECEPTOR AGONISTS |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3998811A (en) * | 1971-03-17 | 1976-12-21 | Crc Compagnia Di Recerca Chimica S.A. | Optically active 1,4-benzodiazepines and process for the preparation thereof |
| HU171033B (hu) * | 1974-05-29 | 1977-10-28 | Richter Gedeon Vegyeszet | Sposob poluchenija proizvodnykh benzodiazepina |
| CA1157855A (en) * | 1980-07-31 | 1983-11-29 | Albert E. Fischli | Benzodiazepine derivatives |
| NL8401907A (nl) * | 1983-06-27 | 1985-01-16 | Sandoz Ag | Spirosuccinimiden en werkwijzen voor het bereiden en toepassen van deze spirosuccinimiden. |
-
1984
- 1984-08-24 DE DE19843431195 patent/DE3431195A1/de not_active Withdrawn
-
1985
- 1985-08-05 NO NO853089A patent/NO161494C/no unknown
- 1985-08-08 US US06/763,746 patent/US4647560A/en not_active Expired - Fee Related
- 1985-08-14 AT AT85110191T patent/ATE46905T1/de not_active IP Right Cessation
- 1985-08-14 EP EP85110191A patent/EP0172526B1/de not_active Expired
- 1985-08-14 DE DE8585110191T patent/DE3573425D1/de not_active Expired
- 1985-08-21 PH PH32676A patent/PH23803A/en unknown
- 1985-08-21 NZ NZ213186A patent/NZ213186A/en unknown
- 1985-08-21 IL IL76153A patent/IL76153A0/xx not_active IP Right Cessation
- 1985-08-22 CA CA000489254A patent/CA1249269A/en not_active Expired
- 1985-08-22 GR GR852035A patent/GR852035B/el unknown
- 1985-08-22 FI FI853229A patent/FI79315C/fi not_active IP Right Cessation
- 1985-08-22 AU AU46574/85A patent/AU574216B2/en not_active Ceased
- 1985-08-22 PT PT81003A patent/PT81003B/pt not_active IP Right Cessation
- 1985-08-23 HU HU853222A patent/HU201933B/hu not_active IP Right Cessation
- 1985-08-23 ZA ZA856409A patent/ZA856409B/xx unknown
- 1985-08-23 ES ES546378A patent/ES8702910A1/es not_active Expired
- 1985-08-23 KR KR1019850006080A patent/KR920000763B1/ko not_active Expired
- 1985-08-23 JP JP60184317A patent/JPS6157582A/ja active Granted
- 1985-08-23 DK DK384585A patent/DK384585A/da not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0172526A1 (de) | 1986-02-26 |
| DK384585D0 (da) | 1985-08-23 |
| FI853229L (fi) | 1986-02-25 |
| KR920000763B1 (ko) | 1992-01-21 |
| PH23803A (en) | 1989-11-03 |
| ES8702910A1 (es) | 1987-01-16 |
| GR852035B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1985-12-18 |
| PT81003A (en) | 1985-09-01 |
| ZA856409B (en) | 1986-04-30 |
| US4647560A (en) | 1987-03-03 |
| NO161494C (no) | 1989-08-23 |
| AU574216B2 (en) | 1988-06-30 |
| FI79315B (fi) | 1989-08-31 |
| DE3431195A1 (de) | 1986-03-06 |
| DE3573425D1 (en) | 1989-11-09 |
| NO853089L (no) | 1986-02-25 |
| JPH0378868B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-12-17 |
| HU201933B (en) | 1991-01-28 |
| PT81003B (pt) | 1987-12-30 |
| ES546378A0 (es) | 1987-01-16 |
| DK384585A (da) | 1986-02-25 |
| HUT39449A (en) | 1986-09-29 |
| EP0172526B1 (de) | 1989-10-04 |
| FI853229A0 (fi) | 1985-08-22 |
| NZ213186A (en) | 1988-04-29 |
| KR860001812A (ko) | 1986-03-22 |
| IL76153A0 (en) | 1985-12-31 |
| CA1249269A (en) | 1989-01-24 |
| FI79315C (fi) | 1989-12-11 |
| ATE46905T1 (de) | 1989-10-15 |
| AU4657485A (en) | 1986-02-27 |
| NO161494B (no) | 1989-05-16 |
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