NO140978B - Analogifremgangsmaate for fremstilling av terapeutisk aktive isokinolinderivater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive isokinolinderivater Download PDFInfo
- Publication number
- NO140978B NO140978B NO743220A NO743220A NO140978B NO 140978 B NO140978 B NO 140978B NO 743220 A NO743220 A NO 743220A NO 743220 A NO743220 A NO 743220A NO 140978 B NO140978 B NO 140978B
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- oxo
- acid
- mixture
- isomers
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 11
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000004965 peroxy acids Chemical class 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- -1 steroid compounds Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- ALGOIGGTYBBGEI-LMQQZZHGSA-N (8R,9S,10S,13S)-17-acetyl-10,13-dimethyl-2,4,5,6,7,8,9,12-octahydro-1H-cyclopenta[a]phenanthrene-3,11-dione Chemical class CC(C1=CC=C2[C@@H]3CCC4CC(CC[C@]4(C)[C@H]3C(C[C@]12C)=O)=O)=O ALGOIGGTYBBGEI-LMQQZZHGSA-N 0.000 description 1
- KTJZDITZKUYYLX-CLWZGTPUSA-N (8S,9S,10S,13R,14S,17S)-17-acetyl-15,15-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,12,14,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-one Chemical class OC1([C@@H]2[C@]([C@H](C1)C(C)=O)(C)CC([C@H]1[C@H]2CCC2CCCC[C@]12C)=O)O KTJZDITZKUYYLX-CLWZGTPUSA-N 0.000 description 1
- IORISFYTXJVNFE-UHFFFAOYSA-N 2,3-dinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O IORISFYTXJVNFE-UHFFFAOYSA-N 0.000 description 1
- GWGBNENHEGYJSN-UHFFFAOYSA-N 2,4-dinitrobenzenesulfonic acid;hydrate Chemical compound O.OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O GWGBNENHEGYJSN-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000005711 Benzoic acid Substances 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
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Description
Fremgangsmåte til fremstilling av en blanding av isomere av et 3«, 23-diacyloxy-16' - eller 16/-lavere alkyl-17(20)-epoxy-21-normetyl-ll-oxo-22 kolen-24(20) -
lakton.
Foreliggende oppfinnelse angår en
fremgangsmåte til fremstilling av nye ste-roide forbindelser, nemlig blandinger av
isomere av 3a, 23-diacyloxy-17(20)- epoxy-21-normetyl-11 -oxo-22-kolen-24( 20) -lakto-ner som er substituert i 16a- eller 16(3-stil-lingen med lavere alkyl, dvs. blandinger av
isomere av 3a, 23-diacyloxy-16a-lavere-alkyl-17(20)-epoxy-21-normetyl-ll-oxo-22-kolen-24(20)-laktoner henholdsvis 3a, 23-diacyloxy-16(3-lavere-alkyl-17(20)-epoxy-21-normetyl-ll-oxo-22-kolen-24(20)-lak-toner.
Disse forbindelser lar seg overføre til
16a-, henholdsvis 16|3-lavere-alkyl-3a, 17a-
dihydroxy-11, 20-pregnandioner ved fremgangsmåte ifølge patent nr. 103 667, og disse forbindelser kan lett omdannes til 16a-henholdsvis til 16(3-lavere-alkyl-17a, 21-di-hydroxy-1, 4 pregnadien-3, 11, 20-trioner. Sistnevnte forbindelser utmerker seg ved en ytterst sterk anti-inflammatorisk virkning.
I fremgangsmåten ifølge oppfinnelsen anvender man som utgangsmateriale en 16a-lavere-alkyl-3a-hydroxy-11, 20-dioxo-21-pregnanglyoxylsyre eller en 16p-lavere-alkyl-3a-hydroxy-ll, 20-dioxo-pregnangly-oxylsyre. Disse forbindelser tilsvarer føl-gende generelle formler:
i hvilke R betegner en lavere alkylgruppe
og R' betegner en acyloxygruppe eller en
hydroxylgruppe.
Disse forbindelser kan fremstilles så-ledes som beskrevet i patent nr. 103 670.
I fremgangsmåten ifølge oppfinnelsen
omsetter man eh 16a-lavere-alkyl-3a- hy-
droxy-11, 20-dioxo-21-pregnanglyoxylsyre eller en 16|3-lavere-alkyl-3a-hydroxy-ll, 20-dioxo-21-pregnanglyoxylsyre med et syre-anhydrid, som eddiksyreanhydrid, under katalytisk innvirkning av en sterk syre, som perklorsyre, hydrogenbromid eller di-nitrobenzensulfonsyre, hvorved man får en
blanding av isomere av et 3a, 23-diacyloxy-16a-lavere-alkyl-21-normetyl-l l-oxo-17
(20), 22-koladien-24 (20) -lakton henholdsvis en blanding av isomere av et 3a, 23-diacyl-
oxy-16p-lavere-alkyl-21-normetyl-ll-oxo-17(20), 22-koladien-24(20)-lakton. Disse forbindelser tilsvarer følgende generelle formler:
I disse formler har R og R' de ovenfor angitte betydninger.
Denne blanding av isomere av et 3a,23-diacyloxy-16a-lavere-alkyl-21-normetyl-ll-oxo-17(20) ,22-koladien-24(20)-lakton eller av isomere av et 3a,23-diacyloxy-16[3-lavere-alkyl-21 -normetyl-11 -oxo-17 (20) ,22-koladien-24(20)-lakton omsettes så med en persyre, som monoperftalsyre, pereddiksyre eller perbenzoesyre, hvorved det dannes en blanding av isomere av et 3a,23-diacyloxy-16a-lavere-alkyl-17(20)-epoxy-21-norm-etyl-ll-oxo-22-kolen-24(20)-lakton, henholdsvis av isomere av et 3«,23-diacyloxy-16|3-lavere-alkyl-17(20)-epoxy-21-norm-etyl-11 -oxo-22-kolen-24 (20) -lakton. Disse forbindelser tilsvarer følgende generelle formler:
I disse formler har R og R' de ovenfor angitte betydninger.
I det følgende beskrives som eksempel en utførelsesform for oppfinnelsen.
Eksempel:
En suspensjon av 1,0 g (2,39 mol) 3 a-hydroxy-16a-metyl-ll,20-dioxo-21-preg-nanglyoxylsyre i 10 ml eddiksyreanhydrid ble tilsatt 30 mg 2,4-dinitrobenzen-sulfon-syre. Det faste stoff gikk fullstendig i opp-løsning etter omkring 15 minutter. Oppløs-ningen ble !derpå omrørt ved 25° C i 2y2 time, hvorpå den ble inndampet i vakuum på vannbad ved 50° C til en tykk sirup. Denne sirup ble oppløst i 25 ml benzen og vasket to ganger med 10 ml porsjoner av en 2,5 N natriumhydroxydoppløsning og med 10 ml vann. Benzenoppløsningen ble tørret med magnesiumsulfat, hvorpå reak-sjonsblandingen ble inndampet i vakuum, hvorpå man fikk 2 g amorft, fast stoff som er en blanding av de isomere av 3a,23-di-acetoxy-16a-metyl-21-normetyl-l 1-oxo-17 (20) ,22-koladien-24 (20) -lakton.
CH,CN
l 2970, E % 432.
maks.
Råproduktet bestående av en blanding av de isomere av 3a,23-diacetoxy- 16a-metyl-21 -normetyl-11 -oxo-17(20),22-koladien-24(20)-lakton ble om-krystallisert fra 4 ml etanol, hvorved man fikk <<>950 mg av forbindelsen, tilsvarende et utbytte på 82 %.
CHSCN
2980, E % 474.
maks.
På lignende måte kan 3a-hydroxy-16(3-metyl-ll,20-dioxo-21-pregnanglyoxylsyre omsettes med eddiksyreanhydrid i nærvær av en katalysator bestående av en sterk syre så at der dannes en blanding av de isomere av 3o,23-diacetoxy-16(3-metyl-21-normetyl-ll-oxo-17(20),22-koladien-24(20)-lakton.
8,5 g av en blanding av de isomere av 3a,23-diacetoxy-16a-metyl-21-normetyl-ll-oxo-17 (20) ,22-koladien-24 (20) -lakton ble tilsatt til 110 ml av en oppløsning av per-
benzoesyre i benzen, og man lot blandingen stå ved 25° C i 140 timer. Den ble derpå av-kjølt til 15° C og vasket med 50 ml vann. Overskuddet av syre ble derpå fjernet ved å ekstrahere tre ganger med 50 ml porsjoner av en 10 %'s natriumbikarbonatoppløs-ning og derpå ble det vasket to ganger med 50 ml porsjoner vann. Det vandige sjikt ble
ettervasket to ganger med 25 ml porsjoner benzen, de organiske ekstrakter ble blandet og tørret over natriumsulfat, filtrert og inndampet i vakuum, hvorved man fikk et oljeaktig residuum. Dette residuum krystal-liserte lett. Utbyttet var kvantitativt. For å fraskille ethylbenzoatet ble det krystallinske residuum oppvarmet under tilbakeløps-kjøling med 160 ml petroleter og filtrert. Det krystallinske bunnfall man herved fikk besto av en blanding av de isomere av 3a, 23-diacetoxy-17(20)-epoxy-16a-metyl-21-normetyl-11 -oxo-22-kolen-24(20)-lakton og veide 8,9 g, hvilket tilsvarer et utbytte på 100%.
CH.,CN
l 2260, E % 228.
maks.
På lignende måte kan en blanding av de isomere av 3a,23-diacetoxy-16p-metyl-21 -normetyl-11 -oxo-17(20) ,22 -koladien-24(20)-lakton omsettes med persyre så at det dannes en blanding av de isomere av de 3a,23-diacetoxy-17(20)-epoxy-16f)-metyl-21-normetyl-ll-oxo-22-kolen-24(20) -lakton.
Claims (1)
- Fremgangsmåte til fremstilling av en blanding av isomere av et 3a,23-diacyloxy-16a- eller 16p-lavere-alkyl-17(20)-epoxy-21-normetyl-ll-oxo-22-kolen-24(20-lakton, som kan anvendes som utgangsmaterialer ved fremstilling av 16a- eller 16p-lavere-alkyl-A1 ■4-pregnadiener med sterk anti-inflammatorisk virkning, og med den generelle formeli hvilken R betegner en lavere alkylgruppe og R' betegner en acyloxygruppe karakterisert ved at man omsetter en 16a-eller 16|3-lavere-alkyl-3-hydroxy-ll,20-di- oxo-21-pregnanglyoxylsyre med et syrean- hydrid i nærvær av en sterk syre, hvorved der dannes en blanding av isomere av et 3a,23-diacyloxy-16a- eller 16p-lavere-alkyl-21-normetyl-ll-oxo-17(20),22-koladien-24(20)-lakton med den generelle formel hvor R og R' har de ovenfor angitte betyd-I ninger, hvorpå man behandler denne blan-, ding med en persyre.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2345422A DE2345422C2 (de) | 1973-09-08 | 1973-09-08 | Substituierte Isochinolyl-arylpiperazine diese enthaltende Arzneimittel sowie Verfahren zu deren Herstellung |
| DE19732345423 DE2345423A1 (de) | 1973-09-08 | 1973-09-08 | Neue substituierte phenylaethylaminderivate, deren saeureadditionssalze, diese enthaltende arzneimittel sowie verfahren zu deren herstellung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO743220L NO743220L (no) | 1975-04-07 |
| NO140978B true NO140978B (no) | 1979-09-10 |
| NO140978C NO140978C (no) | 1979-12-19 |
Family
ID=25765764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO743220A NO140978C (no) | 1973-09-08 | 1974-09-06 | Analogifremgangsmaate for fremstilling av terapeutisk aktive isokinolinderivater |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US3948898A (no) |
| JP (1) | JPS596868B2 (no) |
| AT (1) | AT330777B (no) |
| BG (2) | BG22390A3 (no) |
| CA (1) | CA1025869A (no) |
| CH (2) | CH605778A5 (no) |
| CS (1) | CS185660B2 (no) |
| DD (1) | DD115122A5 (no) |
| DK (1) | DK137124C (no) |
| ES (3) | ES429473A1 (no) |
| FI (1) | FI52219C (no) |
| FR (1) | FR2242979B1 (no) |
| GB (1) | GB1446791A (no) |
| HK (1) | HK4180A (no) |
| HU (1) | HU167869B (no) |
| IE (1) | IE40742B1 (no) |
| IL (1) | IL45609A (no) |
| MY (1) | MY8100330A (no) |
| NL (1) | NL176363C (no) |
| NO (1) | NO140978C (no) |
| PH (1) | PH12918A (no) |
| PL (1) | PL91712B1 (no) |
| RO (1) | RO63655A (no) |
| SE (1) | SE424863B (no) |
| SU (2) | SU545256A3 (no) |
| YU (1) | YU39928B (no) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2639718C2 (de) * | 1976-09-03 | 1987-03-05 | Dr. Karl Thomae Gmbh, 7950 Biberach | 1-[6,7-Dimethoxy-3,4-dihydro-2H-isochinolin-1-on-2-yl]-3-[N-methyl-N-(2-(3,4-dimethoxy-phenyl)-äthyl)-amino]-propan, dessen physiologisch verträgliche Säureadditionssalze und diese Verbindungen enthaltende Arzneimittel |
| DE2702600A1 (de) * | 1977-01-22 | 1978-07-27 | Thomae Gmbh Dr K | Neue aminoalkoxyphenyl-derivate |
| US4619930A (en) * | 1985-01-16 | 1986-10-28 | Bristol-Myers Company | Antipsychotic cyclic imide derivatives of 2-(4-butylpiperazin-1-yl)pyridines, compositions and use |
| JPS6312877U (no) * | 1986-03-05 | 1988-01-27 | ||
| US4876256A (en) * | 1988-04-29 | 1989-10-24 | Merck & Co., Inc. | Alkylpiperazinylpyridines as hypoglycemic agents |
| US5169948A (en) * | 1991-05-22 | 1992-12-08 | American Home Products Corporation | Process and intermediates for the preparation of spiro[isoquinoline-4(1H),3-pyrrolidine]1,2,3,5 (2H)-tetrones which are useful as aldose reductase inhibitors |
| SE9303274D0 (sv) * | 1993-10-07 | 1993-10-07 | Astra Ab | Novel phenylethyl and phenylproplamines |
| BR9813279B1 (pt) | 1997-10-27 | 2010-11-16 | derivado de homopiperazina, composição farmacêutica, e, uso do derivado de homopiperazina. | |
| US20040152710A1 (en) * | 2002-10-15 | 2004-08-05 | Deecher Darlene Coleman | Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms |
| ATE517880T1 (de) * | 2005-01-28 | 2011-08-15 | Boehringer Ingelheim Pharma | Verfahren zur herstellung von isochroman und derivaten davon |
| BRPI0708337A2 (pt) * | 2006-02-28 | 2011-05-24 | Helicon Therapeutics Inc | pipirazinas terapêutica como inibidores pde4 |
| US8927546B2 (en) | 2006-02-28 | 2015-01-06 | Dart Neuroscience (Cayman) Ltd. | Therapeutic piperazines |
| US20240254132A1 (en) * | 2021-07-16 | 2024-08-01 | Denali Therapeutics Inc. | Compounds, compositions and methods |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1185934A (en) * | 1967-06-28 | 1970-03-25 | Pfizer & Co C | Derivatives of 1,3(2H,4H)-Dioxoisoquinoline and preparation thereof |
| SE368009B (no) * | 1971-09-16 | 1974-06-17 | Kabi Ab | |
| GB1424348A (en) * | 1972-11-30 | 1976-02-11 | Wyeth John & Brother Ltd | Isoquinoline derivatives |
-
1974
- 1974-08-08 AT AT651474A patent/AT330777B/de active
- 1974-08-21 FI FI742465A patent/FI52219C/fi active
- 1974-08-23 ES ES429473A patent/ES429473A1/es not_active Expired
- 1974-09-04 US US05/503,072 patent/US3948898A/en not_active Expired - Lifetime
- 1974-09-04 IE IE1838/74A patent/IE40742B1/xx unknown
- 1974-09-04 BG BG027624A patent/BG22390A3/xx unknown
- 1974-09-04 BG BG028726A patent/BG26195A4/xx unknown
- 1974-09-05 YU YU2391/74A patent/YU39928B/xx unknown
- 1974-09-06 PH PH16248A patent/PH12918A/en unknown
- 1974-09-06 CH CH1218974A patent/CH605778A5/xx not_active IP Right Cessation
- 1974-09-06 DD DD180966A patent/DD115122A5/xx unknown
- 1974-09-06 FR FR7430387A patent/FR2242979B1/fr not_active Expired
- 1974-09-06 CS CS7400006150A patent/CS185660B2/cs unknown
- 1974-09-06 RO RO7400079932A patent/RO63655A/ro unknown
- 1974-09-06 HU HUTO980A patent/HU167869B/hu unknown
- 1974-09-06 NO NO743220A patent/NO140978C/no unknown
- 1974-09-06 CA CA208,607A patent/CA1025869A/en not_active Expired
- 1974-09-06 CH CH1601477A patent/CH605779A5/xx not_active IP Right Cessation
- 1974-09-06 NL NLAANVRAGE7411843,A patent/NL176363C/xx not_active IP Right Cessation
- 1974-09-06 GB GB3908374A patent/GB1446791A/en not_active Expired
- 1974-09-06 IL IL45609A patent/IL45609A/en unknown
- 1974-09-06 JP JP49102862A patent/JPS596868B2/ja not_active Expired
- 1974-09-06 SE SE7411312A patent/SE424863B/xx not_active IP Right Cessation
- 1974-09-06 DK DK472774A patent/DK137124C/da not_active IP Right Cessation
- 1974-09-07 PL PL1974173958A patent/PL91712B1/pl unknown
-
1975
- 1975-01-20 ES ES433959A patent/ES433959A1/es not_active Expired
- 1975-01-20 ES ES433958A patent/ES433958A1/es not_active Expired
- 1975-06-20 SU SU2145935A patent/SU545256A3/ru active
- 1975-06-20 SU SU2145942A patent/SU538664A3/ru active
-
1980
- 1980-01-31 HK HK41/80A patent/HK4180A/xx unknown
-
1981
- 1981-12-30 MY MY330/81A patent/MY8100330A/xx unknown
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