DE2157112C3 - Benzodiazepin-Derivat - Google Patents
Benzodiazepin-DerivatInfo
- Publication number
- DE2157112C3 DE2157112C3 DE2157112A DE2157112A DE2157112C3 DE 2157112 C3 DE2157112 C3 DE 2157112C3 DE 2157112 A DE2157112 A DE 2157112A DE 2157112 A DE2157112 A DE 2157112A DE 2157112 C3 DE2157112 C3 DE 2157112C3
- Authority
- DE
- Germany
- Prior art keywords
- dihydrochloride
- monohydrochloride
- flurazepam
- dihydro
- fluorophenyl
- 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.)
- Expired
Links
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 44
- -1 2-diethylaminoethyl Chemical group 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000002775 capsule Substances 0.000 description 20
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 18
- SAADBVWGJQAEFS-UHFFFAOYSA-N flurazepam Chemical compound N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F SAADBVWGJQAEFS-UHFFFAOYSA-N 0.000 description 13
- 229960003528 flurazepam Drugs 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 10
- 229930195725 Mannitol Natural products 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000000594 mannitol Substances 0.000 description 10
- 235000010355 mannitol Nutrition 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000000945 filler Substances 0.000 description 9
- 235000019359 magnesium stearate Nutrition 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 229920002261 Corn starch Polymers 0.000 description 7
- 239000008120 corn starch Substances 0.000 description 7
- 229940099112 cornstarch Drugs 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000000454 talc Substances 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- PUGVROXLRUQCAF-UHFFFAOYSA-N Flurazepam monohydrochloride Chemical compound Cl.N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F PUGVROXLRUQCAF-UHFFFAOYSA-N 0.000 description 5
- 239000002262 Schiff base Substances 0.000 description 5
- 150000004753 Schiff bases Chemical class 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZIIJJOPLRSCQNX-UHFFFAOYSA-N Flurazepam hydrochloride Chemical compound Cl.Cl.N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F ZIIJJOPLRSCQNX-UHFFFAOYSA-N 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 238000002845 discoloration Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000001828 Gelatine Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000002618 waking effect Effects 0.000 description 2
- ZHYMGSPDEVXULU-UHFFFAOYSA-N 1,2-benzodiazepin-3-one Chemical class N1=NC(=O)C=CC2=CC=CC=C21 ZHYMGSPDEVXULU-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 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 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000008101 lactose Substances 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
- 230000000422 nocturnal effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH832571A CH553792A (de) | 1971-06-08 | 1971-06-08 | Verfahren zur herstellung von 7-chlor-1-(2-diaethyl-aminoaethyl)-5-(2-fluorphenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-on-monohydrochlorid. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2157112A1 DE2157112A1 (de) | 1972-12-28 |
| DE2157112B2 DE2157112B2 (de) | 1980-10-09 |
| DE2157112C3 true DE2157112C3 (de) | 1981-09-03 |
Family
ID=4338591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2157112A Expired DE2157112C3 (de) | 1971-06-08 | 1971-11-17 | Benzodiazepin-Derivat |
Country Status (31)
| Country | Link |
|---|---|
| JP (1) | JPS5230568B1 (enExample) |
| AT (1) | AT313281B (enExample) |
| BE (1) | BE777897A (enExample) |
| BG (1) | BG19173A3 (enExample) |
| BR (1) | BR7108123D0 (enExample) |
| CA (1) | CA945989A (enExample) |
| CH (1) | CH553792A (enExample) |
| CS (2) | CS155106B2 (enExample) |
| CY (1) | CY868A (enExample) |
| DD (1) | DD98679A5 (enExample) |
| DE (1) | DE2157112C3 (enExample) |
| DK (1) | DK127506B (enExample) |
| ES (1) | ES397552A1 (enExample) |
| FI (1) | FI51352C (enExample) |
| FR (1) | FR2140371B1 (enExample) |
| GB (1) | GB1331823A (enExample) |
| HU (1) | HU170152B (enExample) |
| IE (1) | IE35846B1 (enExample) |
| IL (1) | IL38252A (enExample) |
| KE (1) | KE2652A (enExample) |
| LU (1) | LU65469A1 (enExample) |
| MX (1) | MX149567A (enExample) |
| MY (1) | MY7400115A (enExample) |
| NL (1) | NL7116376A (enExample) |
| NO (1) | NO133714C (enExample) |
| PH (1) | PH13530A (enExample) |
| PL (1) | PL81437B1 (enExample) |
| RO (2) | RO59000A (enExample) |
| SE (2) | SE388856B (enExample) |
| SU (2) | SU444369A3 (enExample) |
| ZA (1) | ZA717880B (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1199304A1 (en) * | 1997-03-05 | 2002-04-24 | Takeda Chemical Industries, Ltd. | Bicyclic compounds and pharmaceutical composition containing tricyclic compound for treating or preventing sleep disorders |
-
1971
- 1971-02-01 ES ES397552A patent/ES397552A1/es not_active Expired
- 1971-06-08 CH CH832571A patent/CH553792A/xx not_active IP Right Cessation
- 1971-11-15 FI FI713268A patent/FI51352C/fi active
- 1971-11-15 NO NO4214/71A patent/NO133714C/no unknown
- 1971-11-16 SE SE7114654A patent/SE388856B/xx unknown
- 1971-11-16 DK DK561771AA patent/DK127506B/da not_active IP Right Cessation
- 1971-11-17 DE DE2157112A patent/DE2157112C3/de not_active Expired
- 1971-11-17 HU HUHO1433A patent/HU170152B/hu unknown
- 1971-11-18 AT AT996671A patent/AT313281B/de not_active IP Right Cessation
- 1971-11-22 PL PL1971151697A patent/PL81437B1/pl unknown
- 1971-11-23 GB GB5436871A patent/GB1331823A/en not_active Expired
- 1971-11-23 ZA ZA717880A patent/ZA717880B/xx unknown
- 1971-11-23 CY CY868A patent/CY868A/xx unknown
- 1971-11-23 CA CA128,336A patent/CA945989A/en not_active Expired
- 1971-11-24 IE IE1489/71A patent/IE35846B1/xx unknown
- 1971-11-25 BG BG019094A patent/BG19173A3/xx unknown
- 1971-11-29 SU SU1721027A patent/SU444369A3/ru active
- 1971-11-29 NL NL7116376A patent/NL7116376A/xx unknown
- 1971-11-29 SU SU1959119A patent/SU475776A3/ru active
- 1971-11-29 IL IL38252A patent/IL38252A/xx unknown
- 1971-12-02 RO RO68930A patent/RO59000A/ro unknown
- 1971-12-02 RO RO75458A patent/RO58965A/ro unknown
- 1971-12-02 JP JP46096838A patent/JPS5230568B1/ja active Pending
- 1971-12-04 MX MX131834A patent/MX149567A/es unknown
- 1971-12-08 BR BR8123/71A patent/BR7108123D0/pt unknown
- 1971-12-09 PH PH13088A patent/PH13530A/en unknown
- 1971-12-29 DD DD159994A patent/DD98679A5/xx unknown
- 1971-12-30 CS CS752472A patent/CS155106B2/cs unknown
- 1971-12-30 CS CS913171A patent/CS155105B2/cs unknown
-
1972
- 1972-01-11 FR FR7200802A patent/FR2140371B1/fr not_active Expired
- 1972-01-11 BE BE777897A patent/BE777897A/xx not_active IP Right Cessation
- 1972-06-06 LU LU65469A patent/LU65469A1/xx unknown
-
1974
- 1974-12-30 MY MY115/74A patent/MY7400115A/xx unknown
-
1975
- 1975-11-20 SE SE7513088A patent/SE7513088L/xx unknown
-
1976
- 1976-07-21 KE KE2652*UA patent/KE2652A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3143219C2 (enExample) | ||
| DE1793208A1 (de) | Neue cyclische Kohlenwasserstoffverbindungen | |
| DE2445584B2 (de) | L- bzw. DL-2-Methyl-3- (3', 4'-dihydroxyphenyl)-alanin-ester, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE1802394C2 (de) | Arzneimittel mit antihypertensiver Wirkung, die [(2,6-Dichlorbenzyliden)-amino]-guanidin oder ein Säureadditionssalz davon enthalten | |
| DE3125471C2 (de) | Piperazinderivate, Verfahren zu ihrer Herstellung und Arzneimittel, die diese Verbindungen enthalten | |
| DE2846251A1 (de) | Guanidinbenzoesaeureverbindungen, verfahren zu deren herstellung und arzneimittel, welche diese enthalten | |
| DE2439859A1 (de) | Verfahren zur herstellung von 3-(3,4dihydroxy-phenyl)-serin | |
| DE3016752A1 (de) | Verfahren zur herstellung von 2-isopropylaminopyrimidinhydroxy-derivaten | |
| CH634060A5 (de) | Verfahren zur herstellung neuer (3-amino-5-substituierter-6-fluorpyrazinoyl- oder -pyrazinamido)-guanidine und deren derivate. | |
| AT390616B (de) | Verfahren zur herstellung von neuem, kristallinem cephalexinhydrochloridmonohydrat und dessen verwendung zur herstellung eines arzneimittels | |
| DE2157112C3 (de) | Benzodiazepin-Derivat | |
| DE69015834T2 (de) | 6-Chlor-7,8-dihydroxy-1-(4'-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzodiazepin-carbamate als Pro-Arzneimittel. | |
| DE2523250C2 (enExample) | ||
| DE2726849A1 (de) | Dihydro- und tetrahydro-iminothiazine | |
| DE3139554C2 (enExample) | ||
| DE1963317A1 (de) | Chemische Verfahren und Produkte | |
| DE10044905A1 (de) | (2-Azabicyclo[2.2.1]hept-7-yl)methanol-Derivate als nikontinische Acetylcholinrezeptor Agonisten | |
| DE1915230B2 (de) | Hydroxyphenylalkylaminderivate, verfahren zu deren herstellung und arzneimittel auf deren basis | |
| DE3121175A1 (de) | Erythro-1,2,3-triphenyl-1-pentanon-derivate sowie verfahren zu ihrer herstellung und ihre verwendung als arzneimittel | |
| DE3105122C2 (de) | Neue Piperazin-Verbindungen, Verfahren zu ihrer Herstellung und diese enthaltende Immunverstärker | |
| DE2259471C2 (de) | 2-Halogen-9-phenyl-5,6-dihydro-7H-pyrido [2,3-f] [1,4] diazepinderivate | |
| DE1906322A1 (de) | Neue alpha-Alkyl-5-hydroxytryptophanester | |
| DE1518125A1 (de) | Aminosaeureamide und Verfahren zu ihrer Herstellung | |
| AT311363B (de) | Verfahren zur Herstellung von neuen Benzodiazepinderivaten und ihren Säureadditionssalzen | |
| DE2053205A1 (de) | Dihydrofurandenvate und Verfahren zu deren Herstellung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OI | Miscellaneous see part 1 | ||
| C3 | Grant after two publication steps (3rd publication) |