DE2215440A1 - l.S-Dihydro-S-hydroxyo-phenyWH-i^benzodiazepin-2-on-substituierteDiaminoacetate und ihre Säureadditionssalze, Verfahren zu ihrer Herstellung und ihre Verwendung - Google Patents
l.S-Dihydro-S-hydroxyo-phenyWH-i^benzodiazepin-2-on-substituierteDiaminoacetate und ihre Säureadditionssalze, Verfahren zu ihrer Herstellung und ihre VerwendungInfo
- Publication number
- DE2215440A1 DE2215440A1 DE19722215440 DE2215440A DE2215440A1 DE 2215440 A1 DE2215440 A1 DE 2215440A1 DE 19722215440 DE19722215440 DE 19722215440 DE 2215440 A DE2215440 A DE 2215440A DE 2215440 A1 DE2215440 A1 DE 2215440A1
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- hydroxy
- methyl
- benzodiazepin
- dihydro
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000002253 acid Substances 0.000 title claims description 10
- 150000003839 salts Chemical class 0.000 title claims description 9
- MAEDLSNGVQYGPK-UHFFFAOYSA-N 2,2-diaminoacetic acid Chemical class NC(N)C(O)=O MAEDLSNGVQYGPK-UHFFFAOYSA-N 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 10
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical group CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 150000003254 radicals Chemical class 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229940049706 benzodiazepine Drugs 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid group Chemical group C(\C=C/C(=O)O)(=O)O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 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 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
- 239000011976 maleic acid Substances 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 239000001384 succinic acid Substances 0.000 claims description 2
- 150000004985 diamines Chemical class 0.000 claims 3
- 125000005059 halophenyl group Chemical group 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- XNEFVTBPCXGIRX-UHFFFAOYSA-N methanesulfinic acid Chemical compound CS(O)=O XNEFVTBPCXGIRX-UHFFFAOYSA-N 0.000 claims 1
- 101150083749 nicC gene Proteins 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 1
- OSHVGUAPPIYWIS-UHFFFAOYSA-N piperazin-1-ium;acetate Chemical compound CC(O)=O.C1CNCCN1 OSHVGUAPPIYWIS-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000000460 chlorine Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- -1 üthoxy Chemical group 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229940089960 chloroacetate Drugs 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 4
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- IHTYTYHXCRAMAV-UHFFFAOYSA-N acetic acid;dihydrochloride Chemical compound Cl.Cl.CC(O)=O IHTYTYHXCRAMAV-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- FOCAUTSVDIKZOP-UHFFFAOYSA-M chloroacetate Chemical compound [O-]C(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-M 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ZAQRIDPUFKWJDQ-UHFFFAOYSA-N acetic acid;hydrate;hydrochloride Chemical compound O.Cl.CC(O)=O ZAQRIDPUFKWJDQ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 150000004683 dihydrates Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose 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
- 230000037023 motor activity Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- KUNAEPADWAFUHL-UHFFFAOYSA-N 7-chloro-5-phenyl-2,3-dihydro-1h-1,4-benzodiazepin-3-ol Chemical compound N=1C(O)CNC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 KUNAEPADWAFUHL-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 206010012225 Delirium tremens Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010027646 Miosis Diseases 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- UTKBLLDLHPDWDU-ODZAUARKSA-N acetic acid;(z)-but-2-enedioic acid Chemical compound CC(O)=O.OC(=O)\C=C/C(O)=O UTKBLLDLHPDWDU-ODZAUARKSA-N 0.000 description 1
- ZXPJBQLFCRVBDR-UHFFFAOYSA-N acetic acid;methanesulfonic acid Chemical compound CC(O)=O.CS(O)(=O)=O ZXPJBQLFCRVBDR-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000001914 calming effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- CKQQMPJQZXIYMJ-UHFFFAOYSA-N dihydrate;dihydrochloride Chemical compound O.O.Cl.Cl CKQQMPJQZXIYMJ-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- FJIKWRGCXUCUIG-UHFFFAOYSA-N lormetazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl FJIKWRGCXUCUIG-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
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- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (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)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12963871A | 1971-03-30 | 1971-03-30 | |
| US05/223,712 US4065451A (en) | 1971-03-30 | 1972-02-04 | 1,3-Dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one, substituted diamino acetate esters and their acid salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2215440A1 true DE2215440A1 (de) | 1972-10-19 |
Family
ID=26827785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19722215440 Withdrawn DE2215440A1 (de) | 1971-03-30 | 1972-03-29 | l.S-Dihydro-S-hydroxyo-phenyWH-i^benzodiazepin-2-on-substituierteDiaminoacetate und ihre Säureadditionssalze, Verfahren zu ihrer Herstellung und ihre Verwendung |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US4065451A (enExample) |
| JP (1) | JPS5724347B1 (enExample) |
| CH (1) | CH583209A5 (enExample) |
| DE (1) | DE2215440A1 (enExample) |
| FR (1) | FR2132195B1 (enExample) |
| GB (1) | GB1351549A (enExample) |
| IE (1) | IE36213B1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT361492B (de) * | 1978-12-18 | 1981-03-10 | Gerot Pharmazeutika | Verfahren zur herstellung von neuen 3-hydroxy- 1,4-benzodiazepin-2-onen |
| IT1165588B (it) * | 1983-03-23 | 1987-04-22 | Medosan Ind Biochimi | 1,4 benzodiazepine terapeuticamente attive |
| CA1332410C (en) * | 1984-06-26 | 1994-10-11 | Roger M. Freidinger | Benzodiazepine analogs |
| US4820834A (en) * | 1984-06-26 | 1989-04-11 | Merck & Co., Inc. | Benzodiazepine analogs |
| EP3468545A4 (en) | 2016-06-08 | 2020-07-22 | President and Fellows of Harvard College | METHODS AND COMPOSITIONS FOR REDUCING TACTILE DYSFUNCTION AND ANXIETY ASSOCIATED WITH AUTISM SPECTRUM DISORDER, RETT SYNDROME AND FRAGILE X SYNDROME |
| EP3797097A4 (en) | 2018-05-22 | 2022-03-09 | President and Fellows of Harvard College | Compositions and methods for reducing tactile dysfunction, anxiety, and social impairment |
| US11434244B2 (en) | 2018-05-29 | 2022-09-06 | President And Fellows Of Harvard College | Compositions and methods for reducing tactile dysfunction, anxiety, and social impairment |
| EP3946390A4 (en) | 2019-03-25 | 2022-12-21 | President and Fellows of Harvard College | COMPOSITIONS AND METHODS TO REDUCE TACTILE DYSFUNCTION, ANXIETY AND SOCIAL DISABILITIES |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL298071A (enExample) * | 1963-06-04 | |||
| FR135F (enExample) * | 1964-08-13 |
-
1972
- 1972-02-04 US US05/223,712 patent/US4065451A/en not_active Expired - Lifetime
- 1972-03-22 GB GB1331572A patent/GB1351549A/en not_active Expired
- 1972-03-23 IE IE375/72A patent/IE36213B1/xx unknown
- 1972-03-29 FR FR7211084A patent/FR2132195B1/fr not_active Expired
- 1972-03-29 JP JP3152872A patent/JPS5724347B1/ja active Pending
- 1972-03-29 DE DE19722215440 patent/DE2215440A1/de not_active Withdrawn
- 1972-03-30 CH CH482272A patent/CH583209A5/xx not_active IP Right Cessation
Non-Patent Citations (1)
| Title |
|---|
| Arzneim.-Forsch., 15, 359, 1965 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US4065451A (en) | 1977-12-27 |
| GB1351549A (en) | 1974-05-01 |
| FR2132195A1 (enExample) | 1972-11-17 |
| CH583209A5 (enExample) | 1976-12-31 |
| JPS5724347B1 (enExample) | 1982-05-24 |
| FR2132195B1 (enExample) | 1976-07-02 |
| IE36213L (en) | 1972-09-30 |
| IE36213B1 (en) | 1976-09-15 |
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| OD | Request for examination | ||
| 8128 | New person/name/address of the agent |
Representative=s name: SCHWABE, H., DIPL.-ING. SANDMAIR, K., DIPL.-CHEM. |
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| 8125 | Change of the main classification |
Ipc: C07D401/12 |
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| 8139 | Disposal/non-payment of the annual fee |