NO143347B - Utgangsmateriale for fremstilling av benzodiazepinderivater - Google Patents
Utgangsmateriale for fremstilling av benzodiazepinderivater Download PDFInfo
- Publication number
- NO143347B NO143347B NO76761580A NO761580A NO143347B NO 143347 B NO143347 B NO 143347B NO 76761580 A NO76761580 A NO 76761580A NO 761580 A NO761580 A NO 761580A NO 143347 B NO143347 B NO 143347B
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- carbon atoms
- benzodiazepine derivatives
- benzoyloxy
- hydroxy
- Prior art date
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- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title claims 2
- 239000000463 material Substances 0.000 title description 5
- 150000001557 benzodiazepines Chemical class 0.000 title 1
- -1 cyano, carboxy, amino, carbamoyl Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000005544 phthalimido group Chemical group 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/5545—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having eight-membered rings not containing additional condensed or non-condensed nitrogen-containing 3-7 membered rings
-
- 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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, ***e
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
- C07D245/04—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D245/06—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
Fremgangsmåte til fremstilling av 16a-methyl-pregnan-3a,
17a-diol-ll,20-dion.
Foreliggende oppfinnelse angår en kuum. Residuet ekstraheres med benzen, og fremgangsmåte til fremstilling av 16a- benzenekstraktet filtreres for å fjerne methyl-pregnan-3a,17a-diol-ll,20-dion. uoppløst materiale. Benzenekstraktet inn-Denne forbindelse kan anvendes som dampes til et volum på 100 ml og tilsettes mellomprodukt ved fremstillingen av 16a- <p>etrolether til det punkt hvor væsken blir methyl-l,4-pregnadien-17a-ol-3,20-dion- uklar. Den herved erholdte oppløsning ad-forbindelser. Sistnevnte forbindelser har en sorberes på 660 g syrevasket aluminium-sterk anti-inflammatorisk virkning og er °xyd, hvorpå det adsorberte materiale vas-særlig aktive til behandling av arthritis og kes med 2 hter petrolether. Det adsorberte lignende sykdommer. materiale elueres derpå med en blanding
Fremgangsmåten ifølge oppfinnelsen av petrolether og ether i mengdeforholdet er karakterisert ved at man omsetter enol- 85:15. De første fire liter av eluatet opp-acetatet av 16a-methyl-17,20-pregnen-3a, samles og inndampes til tørrhet i vakuum, 20-diol-ll-on med perbenzoesyre, hvorved hvorved man får en blanding av enolaceta-der dannes 16a-methyl-17a,20-epoxy-preg- ter som inneholder 16a-methyl-17(20)-nan-3a,20-diol-ll-on-3,20-diacetat, hvorpå <p>re<g>nen-3a,20-diol-ll-on-3,20-diacetat.
man hydrolyserer sistnevnte forbindelse
med kaliumbikarbonat i methanol til den B: Fremstilling av sluttproduktet, ønskede forbindelse.
I det følgende beskrives som eksempel Ca. 14 g av den således erholdte blån-en utførelsesform for oppfinnelsen. ding av enolacetater oppløses i 50 ml benzen, og oppløsningen behandles med et Eksempel — A: Fremstilling av utgangs- overskudd av perbenzoesyre i et tidsrom materialet. på 16 timer. Reaksjonsblandingen ristes med fortynnet vandig kaliumhydroxydoppløs-En oppløsning av 22 g 16a-methyl- ning inntil benzenskiktet er fritt for per-pregnan-3a-ol-ll,20-dion-21-acetat og 1 g benzoesyre, hvorpå benzenskiktet vaskes p-toluensulfonsyre i 250 ml eddiksyrean- med vann til det er nøytralt og tørres. Opp-hydrid oppvarmes under tilbakeløpskjøling løsningsmidlet fordampes så i vakuum, og i nitrogenatmosfære i et tidsrom på hvorved man får et krystallinsk stoff som omkring 3 døgn. Derpå tilsettes 2 g vann- består av 16a-methyl-17a,20-epoxy-preg-fritt kaliumacetat, og de flyktige oppløs- nan-3a,20-diol-ll-on-3,20-diacetat. Dette ningsmidler adskilles ved destillasjon i va- stoff oppløses uten å renses i 200 ml metha-noi, 120 ml vann og 10 g kaliumbikarbonat. Den herved erholdte oppløsning oppvarmes under tilbakeløpskjøling og i nitrogenatmosfære i 16 timer. Methanolen fordampes i vakuum fra hydrolyseoppløsningen og oppløsningen og residuet bestående av et oljeaktig stoff ekstraheres fra den vandige oppløsning med kloroform. Kloroformeks-traktet vaskes med vann til det er nøytralt, tørres og koroformen fordampes under for-minsket trykk. Residuet, bestående av et oljeaktig stoff, tritureres med ether, og det herved dannede krystallinske stoff omkrys-talliseres fra en blanding av ethylacetat og petrolether, hvorved man får 16a-methyl-pregnan-3a,17a-diol-ll,20-dion.
Fremgangsmåte til fremstilling av 16a-methyl-pregnan-3a,17a-diol-ll,20-dion som kan anvendes som mellomprodukt ved fremstillingen av 16a-methyl-l,4-pregnadi-en-17a-ol-3,20-dion-forbindelser, karakterisert ved at man omsetter enol-acetatet av 16a-methyl-17(20)-pregnen-3a, 20-diol-ll-on med perbenzoesyre, hvorved der dannes 16a-methyl-17a,20-epoxy-preg-nan-3a,20-diol-ll-on-3,20-diacetat, hvorpå man hydrolyserer sistnevnte forbindelse med kaliumbikarbonat i methanol til den ønskede forbindelse.
Claims (1)
- Utgangsmateriale for fremstilling av nye benzodiazepin-derivater med den generelle formel:og syreaddisjonssalter derav, hvor R er hydrogen, lavere alkyl, benzyl, 2-klorethyl eller 2-methoxyethyl, R2er klor, brom, hydroxy, rettkjedet eller forgrenet alkoxy med 1-5 carbonatomer, ethoxycarbonyl, cyano, carboxy, amino, carbamoyl, methyl-carbonylamino, ethoxycarbonylamino, isopropylcarbamoyl, methyl-carbamoyloxy, ethylcarbamoyloxy, fenoxy, klorfenoxy, benzoyloxy, fenylthio, benzylamino, trimethoxybenzoylamino, fenylcarbamoyloxy, ureido, methylureido, isopropylureido, fenylureido, fthalimido, methylpiperazino, morfolino eller piperidino, og A og B er benzenringer som kan være substituert med 1-3 substituenter fra gruppen bestående av halogen, alkyl med 1-4 carbonatomer, alkoxy med 1-4 carbonatomer, eller trifluor-methyl, eller en nitrogruppe alene eller sammen med en av de ovennevnte substituenter, eller A kan være substituert med methyl-thio eller et hylendioxy; karakterisert vedat de er acyldiaminer med formelen:eller syreaddisjonssalter derav, hvor A, B og R.^ er som ovenfor angitt, og R er hydroxy, lavere alkanoyloxy eller benzoyloxy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO76761580A NO143347C (no) | 1972-05-03 | 1976-05-07 | Utgangsmateriale for fremstilling av benzodiazepinderivater |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2221558A DE2221558C2 (de) | 1972-05-03 | 1972-05-03 | 5-Phenyl-2,3-dihydro-1H-1,4-benzodiazepine und ihre Säureadditionssalze, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| NO1797/73A NO142866C (no) | 1972-05-03 | 1973-05-02 | Nye benzodiazepinderivater for anvendelse som ugangsmateriale og fremgangsmaate ved fremstilling derav |
| NO76761580A NO143347C (no) | 1972-05-03 | 1976-05-07 | Utgangsmateriale for fremstilling av benzodiazepinderivater |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO761580L NO761580L (no) | 1973-11-06 |
| NO143347B true NO143347B (no) | 1980-10-13 |
| NO143347C NO143347C (no) | 1981-01-21 |
Family
ID=5843904
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO1797/73A NO142866C (no) | 1972-05-03 | 1973-05-02 | Nye benzodiazepinderivater for anvendelse som ugangsmateriale og fremgangsmaate ved fremstilling derav |
| NO75751349A NO145761C (no) | 1972-05-03 | 1975-04-16 | Benzodiazocinderivater for anvendelse som utgangsmaterialer ved fremstilling av benzodiazepinderivater, og en ny fremgangsmaate for fremstilling av disse benzodiazocinderivater |
| NO76761580A NO143347C (no) | 1972-05-03 | 1976-05-07 | Utgangsmateriale for fremstilling av benzodiazepinderivater |
| NO780402A NO142476C (no) | 1972-05-03 | 1978-02-06 | Fremgangsmaate ved fremstilling av benzodiazepinderivater |
| NO793012A NO144386C (no) | 1972-05-03 | 1979-09-19 | Fremgangsmaate ved fremstilling av benzodiazepinderivater |
| NO793013A NO144885C (no) | 1972-05-03 | 1979-09-19 | Analogifremgangsmaate ved fremstilling av terapeutisk aktive benzodiazepinderivater |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO1797/73A NO142866C (no) | 1972-05-03 | 1973-05-02 | Nye benzodiazepinderivater for anvendelse som ugangsmateriale og fremgangsmaate ved fremstilling derav |
| NO75751349A NO145761C (no) | 1972-05-03 | 1975-04-16 | Benzodiazocinderivater for anvendelse som utgangsmaterialer ved fremstilling av benzodiazepinderivater, og en ny fremgangsmaate for fremstilling av disse benzodiazocinderivater |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO780402A NO142476C (no) | 1972-05-03 | 1978-02-06 | Fremgangsmaate ved fremstilling av benzodiazepinderivater |
| NO793012A NO144386C (no) | 1972-05-03 | 1979-09-19 | Fremgangsmaate ved fremstilling av benzodiazepinderivater |
| NO793013A NO144885C (no) | 1972-05-03 | 1979-09-19 | Analogifremgangsmaate ved fremstilling av terapeutisk aktive benzodiazepinderivater |
Country Status (18)
| Country | Link |
|---|---|
| US (6) | US3998809A (no) |
| JP (3) | JPS5541231B2 (no) |
| AT (3) | AT327919B (no) |
| BE (1) | BE799001A (no) |
| CA (3) | CA1009232A (no) |
| CH (5) | CH611608A5 (no) |
| DD (1) | DD105222A5 (no) |
| DE (3) | DE2265371C3 (no) |
| DK (3) | DK147050C (no) |
| ES (1) | ES414279A1 (no) |
| FR (3) | FR2183735B1 (no) |
| GB (3) | GB1429667A (no) |
| IL (5) | IL42158A (no) |
| NL (1) | NL179111C (no) |
| NO (6) | NO142866C (no) |
| SE (3) | SE409709B (no) |
| SU (2) | SU625607A3 (no) |
| ZA (1) | ZA733013B (no) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4244869A (en) * | 1972-05-03 | 1981-01-13 | Kali-Chemie A.G. | Benzodiazepine derivatives and process of making them |
| DE2520937C3 (de) * | 1975-05-10 | 1978-10-12 | Kali-Chemie Ag, 3000 Hannover | 7-Brom-1 -methyl^-alkoxymethyl-S-(2-halogenphenyl)-lH-23-dihydro-l,4benzodiazepinderivate, deren Säureadditionssalze und pharmazeutische Präparate |
| DE2265371C3 (de) * | 1972-05-03 | 1980-12-11 | Kali-Chemie Ag, 3000 Hannover | N-(3-Benzoylaminopropyl)-aniline |
| DE2720968C2 (de) * | 1977-05-10 | 1986-05-07 | Kali-Chemie Pharma Gmbh, 3000 Hannover | N↓1↓-Acyl-2-hydroxy-1,3-diaminopropane und Arzneimittel |
| DE2720908A1 (de) * | 1977-05-10 | 1978-11-23 | Kali Chemie Pharma Gmbh | Arzneimittel mit ulkustherapeutischem effekt |
| ES469020A1 (es) * | 1977-05-10 | 1979-09-01 | Kali Chemie Pharma Gmbh | Procedimiento para la preparacion de nuevos 1-acil-2-hidroxi-1,3-diaminopropanos |
| US4123430A (en) * | 1977-11-10 | 1978-10-31 | G. D. Searle & Co. | 2-Aryl-4-(1-piperazinyl)-3H-1,5-benzodiazepines |
| DE2754112A1 (de) * | 1977-12-05 | 1979-06-13 | Kali Chemie Pharma Gmbh | 1,4-benzodiazepinderivate, ihre salze und diese verbindungen enthaltende arzneipraeparate |
| DE2810349A1 (de) * | 1978-03-10 | 1979-09-20 | Kali Chemie Pharma Gmbh | Verfahren zur herstellung von 3-hydroxy-6-phenyl-1,2,3,4-tetrahydro- 1,5-benzodiazocinen |
| US4368159A (en) * | 1978-05-15 | 1983-01-11 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
| US4368158A (en) * | 1978-05-15 | 1983-01-11 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
| US4371468A (en) * | 1978-05-15 | 1983-02-01 | Hoffmann-La Roche Inc. | Intermediates to produce imidazodiazepines |
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| BR0013616B1 (pt) | 1999-08-27 | 2011-12-27 | composiÇço de alvejamento e composto catalisador orgÂnico de lavanderia. | |
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| US2721215A (en) * | 1952-06-12 | 1955-10-18 | Hoffmann La Rache Inc | Diphenylacetyl diamines |
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| GB1374366A (en) * | 1972-07-21 | 1974-11-20 | Science Union & Cie | Propanol derivatives and a process for their preparation |
| US3957870A (en) * | 1973-07-19 | 1976-05-18 | Imperial Chemical Industries Limited | Organic compounds |
-
1972
- 1972-05-03 DE DE2265371A patent/DE2265371C3/de not_active Expired
- 1972-05-03 DE DE2221558A patent/DE2221558C2/de not_active Expired
- 1972-05-03 DE DE2265370A patent/DE2265370C2/de not_active Expired
-
1973
- 1973-04-16 DD DD170247A patent/DD105222A5/xx unknown
- 1973-04-19 NL NLAANVRAGE7305570,A patent/NL179111C/xx not_active IP Right Cessation
- 1973-04-25 GB GB3581775A patent/GB1429667A/en not_active Expired
- 1973-04-25 GB GB2491075A patent/GB1429666A/en not_active Expired
- 1973-04-25 GB GB1974173A patent/GB1429665A/en not_active Expired
- 1973-04-26 CH CH1605677A patent/CH611608A5/xx not_active IP Right Cessation
- 1973-04-26 CH CH598873A patent/CH605834A5/xx not_active IP Right Cessation
- 1973-04-26 CH CH1605777A patent/CH611609A5/xx not_active IP Right Cessation
- 1973-04-26 CH CH1605577A patent/CH611607A5/xx not_active IP Right Cessation
- 1973-04-30 CA CA169,889A patent/CA1009232A/en not_active Expired
- 1973-04-30 CA CA169,890A patent/CA984388A/en not_active Expired
- 1973-05-01 IL IL42158A patent/IL42158A/xx unknown
- 1973-05-01 US US05/355,986 patent/US3998809A/en not_active Expired - Lifetime
- 1973-05-01 IL IL47693A patent/IL47693A/xx unknown
- 1973-05-01 IL IL48141A patent/IL48141A/xx unknown
- 1973-05-01 JP JP4900373A patent/JPS5541231B2/ja not_active Expired
- 1973-05-02 SE SE7306128A patent/SE409709B/sv unknown
- 1973-05-02 FR FR7315752A patent/FR2183735B1/fr not_active Expired
- 1973-05-02 NO NO1797/73A patent/NO142866C/no unknown
- 1973-05-02 BE BE130663A patent/BE799001A/xx not_active IP Right Cessation
- 1973-05-02 DK DK238573A patent/DK147050C/da not_active IP Right Cessation
- 1973-05-02 ES ES414279A patent/ES414279A1/es not_active Expired
- 1973-05-03 ZA ZA733013A patent/ZA733013B/xx unknown
- 1973-05-03 AT AT389873A patent/AT327919B/de not_active IP Right Cessation
- 1973-05-03 AT AT143875*1A patent/AT327927B/de not_active IP Right Cessation
- 1973-05-03 AT AT389973A patent/AT327920B/de not_active IP Right Cessation
- 1973-05-03 SU SU731918571A patent/SU625607A3/ru active
- 1973-05-03 SU SU1920527A patent/SU526290A3/ru active
-
1974
- 1974-12-19 FR FR7442122A patent/FR2248278B1/fr not_active Expired
-
1975
- 1975-04-16 NO NO75751349A patent/NO145761C/no unknown
- 1975-07-11 IL IL47693A patent/IL47693A0/xx unknown
- 1975-09-19 IL IL48141A patent/IL48141A0/xx unknown
-
1976
- 1976-04-02 FR FR7609742A patent/FR2296616A1/fr active Granted
- 1976-05-07 NO NO76761580A patent/NO143347C/no unknown
- 1976-05-12 US US05/685,537 patent/US4096141A/en not_active Expired - Lifetime
- 1976-09-02 CA CA260,433A patent/CA1020570A/en not_active Expired
- 1976-09-23 US US05/725,989 patent/US4098786A/en not_active Expired - Lifetime
- 1976-10-04 US US05/729,142 patent/US4216167A/en not_active Expired - Lifetime
- 1976-12-29 SE SE7614681A patent/SE7614681L/xx not_active Application Discontinuation
- 1976-12-29 SE SE7614680A patent/SE422460B/xx unknown
-
1977
- 1977-05-20 DK DK222977A patent/DK144969C/da not_active IP Right Cessation
- 1977-05-20 DK DK223077A patent/DK223077A/da unknown
- 1977-12-09 JP JP52148667A patent/JPS5813535B2/ja not_active Expired
- 1977-12-09 JP JP52148666A patent/JPS589101B2/ja not_active Expired
-
1978
- 1978-01-01 CH CH1605877A patent/CH620423A5/de not_active IP Right Cessation
- 1978-01-23 US US05/871,741 patent/US4243585A/en not_active Expired - Lifetime
- 1978-02-06 NO NO780402A patent/NO142476C/no unknown
-
1979
- 1979-09-19 NO NO793012A patent/NO144386C/no unknown
- 1979-09-19 NO NO793013A patent/NO144885C/no unknown
-
1984
- 1984-04-24 US US06/602,279 patent/US4595531A/en not_active Expired - Fee Related
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