NO123817B - - Google Patents
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- Publication number
- NO123817B NO123817B NO1966/69A NO196669A NO123817B NO 123817 B NO123817 B NO 123817B NO 1966/69 A NO1966/69 A NO 1966/69A NO 196669 A NO196669 A NO 196669A NO 123817 B NO123817 B NO 123817B
- Authority
- NO
- Norway
- Prior art keywords
- carboxylic acid
- ethylindole
- solution
- indole derivatives
- dimethylamine
- Prior art date
Links
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 229940054051 antipsychotic indole derivative Drugs 0.000 claims description 5
- 150000002475 indoles Chemical class 0.000 claims description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- XOALTXJYIZPUCD-UHFFFAOYSA-N 3-ethyl-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2C(CC)=C(C(O)=O)NC2=C1 XOALTXJYIZPUCD-UHFFFAOYSA-N 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- -1 for example Chemical compound 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- HZLHZWIVSRYPEV-UHFFFAOYSA-N 3-ethyl-1H-indole-2-carboxamide Chemical compound C(C)C1=C(NC2=CC=CC=C12)C(=O)N HZLHZWIVSRYPEV-UHFFFAOYSA-N 0.000 description 2
- HYGCGTNJRRNCGP-UHFFFAOYSA-N 3-ethyl-n-methyl-1h-indole-2-carboxamide Chemical compound C1=CC=C2C(CC)=C(C(=O)NC)NC2=C1 HYGCGTNJRRNCGP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IPCFRNXNJNVMTM-UHFFFAOYSA-N 3-ethyl-1H-indole-2-carbonyl azide Chemical compound C(C)C1=C(NC2=CC=CC=C12)C(=O)N=[N+]=[N-] IPCFRNXNJNVMTM-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- CLRSZXHOSMKUIB-UHFFFAOYSA-M benzenediazonium chloride Chemical compound [Cl-].N#[N+]C1=CC=CC=C1 CLRSZXHOSMKUIB-UHFFFAOYSA-M 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- PUTGRHQJZXLFEJ-UHFFFAOYSA-N ethyl 3-ethyl-1h-indole-2-carboxylate Chemical compound C1=CC=C2C(CC)=C(C(=O)OCC)NC2=C1 PUTGRHQJZXLFEJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
Classifications
-
- E—FIXED CONSTRUCTIONS
- E06—DOORS, WINDOWS, SHUTTERS, OR ROLLER BLINDS IN GENERAL; LADDERS
- E06B—FIXED OR MOVABLE CLOSURES FOR OPENINGS IN BUILDINGS, VEHICLES, FENCES OR LIKE ENCLOSURES IN GENERAL, e.g. DOORS, WINDOWS, BLINDS, GATES
- E06B7/00—Special arrangements or measures in connection with doors or windows
- E06B7/02—Special arrangements or measures in connection with doors or windows for providing ventilation, e.g. through double windows; Arrangement of ventilation roses
- E06B7/04—Special arrangements or measures in connection with doors or windows for providing ventilation, e.g. through double windows; Arrangement of ventilation roses with ventilation wings
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F24—HEATING; RANGES; VENTILATING
- F24F—AIR-CONDITIONING; AIR-HUMIDIFICATION; VENTILATION; USE OF AIR CURRENTS FOR SCREENING
- F24F7/00—Ventilation
-
- E—FIXED CONSTRUCTIONS
- E06—DOORS, WINDOWS, SHUTTERS, OR ROLLER BLINDS IN GENERAL; LADDERS
- E06B—FIXED OR MOVABLE CLOSURES FOR OPENINGS IN BUILDINGS, VEHICLES, FENCES OR LIKE ENCLOSURES IN GENERAL, e.g. DOORS, WINDOWS, BLINDS, GATES
- E06B7/00—Special arrangements or measures in connection with doors or windows
- E06B7/02—Special arrangements or measures in connection with doors or windows for providing ventilation, e.g. through double windows; Arrangement of ventilation roses
- E06B7/04—Special arrangements or measures in connection with doors or windows for providing ventilation, e.g. through double windows; Arrangement of ventilation roses with ventilation wings
- E06B7/06—Special arrangements or measures in connection with doors or windows for providing ventilation, e.g. through double windows; Arrangement of ventilation roses with ventilation wings with one ventilation wing only
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F24—HEATING; RANGES; VENTILATING
- F24F—AIR-CONDITIONING; AIR-HUMIDIFICATION; VENTILATION; USE OF AIR CURRENTS FOR SCREENING
- F24F13/00—Details common to, or for air-conditioning, air-humidification, ventilation or use of air currents for screening
- F24F13/08—Air-flow control members, e.g. louvres, grilles, flaps or guide plates
Landscapes
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Combustion & Propulsion (AREA)
- Mechanical Engineering (AREA)
- General Engineering & Computer Science (AREA)
- Civil Engineering (AREA)
- Structural Engineering (AREA)
- Hinges (AREA)
- Indole Compounds (AREA)
- Specific Sealing Or Ventilating Devices For Doors And Windows (AREA)
Description
Fremgangsmåte for fremstilling av terapeutisk virksomme indolderivater.
Nærværende oppfinnelse vedrører en
fremgangsmåte for fremstilling av nye indolderivater, som har verdifulle terapeu-tiske egenskaper.
De nye indolderivater etter nærværende oppfinnelse består av forbindelsene med
følgende generelle formel I:
i hvilken A betyr en enkel binding eller en
-NH-gruppe, og Ri og Ra er samme eller forskjellige og betyr vannstof f atomer eller
metylgrupper.
Ifølge nærværende oppfinnelse fremstilles nevnte indolderivater ved innvirkning av ammoniakk, et hydrazin eller mo-no- eller dimetylamin på et egnet derivat
av 3-etylindol-2-karboksylsyre som, f. eks.,
syrekloridet, azidet eller en ester. Reaksjo-nen utføres under betingelser normalt an-vendt for omdannelsen av et karboksyl-syrederivat til det tilsvarende amid eller
hydrazid.
Forbindelsene etter oppfinnelsen er
særlig virksomme som antikonvulsante og
medullære undertrykkere. Den siste egen-skap kan demonstreres f. eks. som antago-nistisk virkning mot stryknin [se f. eks.
F. M. Berger, Pharmaceutical Reviews 2,
274 (1949)]. De er også effektive når brukt
i tilstrekkelig høy dosering som potentiato-rer for narkose. De kan brukes som ikke hypnotiske sedativer, særlig ved behand-ling av angstfornemmelser og nervøse li-delser. På grunn av sine sedative egenskaper har de også en gunstig effekt ved be-handling av forhøyd blodtrykk. Spesielle forbindelser av særlig betydning er: 3-etylindol-2-karboksylsyre-hydrazid, 3-etylindol-2-karboksylsyre-dimetylamid, 3-etylindol-2-karboksylsyre-monometyl-amid og 3-etylindol-2-karboksylsyre-amid. Oppfinnelsen kan illustreres ved føl-gende eksempler; de angitte smeltepunk-ter er bestemt med Koflerapparatet.
Eksempel 1: Etyl-3-etylidol-2-karboksylat (51 g) og-hydrazinhydrat (120 cm<3>) oppvarmes under tilbakeløp i 3 timer. Ved avkjøling skilles det faste fra, vaskes med vann (4 x 125 cm<3>) og tørres i vakuum. 3-etylindol-2-karbok sylsyrehydrazid (46,5 g) oppnås, sm.p. 183° C.
Etyl-3-etylindol-2-karboksylat (sm.p. 124° C) oppnås ved innvirkning av ben-zendiazoniumklorid på et etyl-a-acetyl-va-lerat i alkoholisk kalium (Burton, Am. Chem. Journ. 3, 385 (1881).
Eksempel 2:
En oppløsning i eter av 3-etylindol-2-karboksylsyre-azid fremstilles ved innvirkning på 3-etylindol-2-karboksylsyrehydra-zid (34 g) (oppnådd som i eksempel 1) i dioksan (750 cm<3>) av natriumnitrit (12 g) oppløst i vann (150 cm<3>) fulgt av n-saltsyre (20 cm<3>), idet temperaturen holdes ved ca. +4° C, fulgt av fortynning med vann (1500 cm<3>) og gjenoppløsning av det faste stoff i eter (300 cm<3>). Til den slik oppnådde oppløsning tilsettes derpå en oppløsning av dimetylamin (150 g) i eter (500 cm<3>) under omrøring, idet temperaturen holdes ved ca. 0° C. Blandingen røres i en time og tillates å stå over natten ved 0° C. Eteroppløsnin-gen rystes med en mettet vandig oppløsning av natrium-bikarbonat (300 cm<3>), kloro-form (300 cm<3>) tilsettes, og det organiske lag skilles fra, vaskes med vann og tørres over kaliumkarbonat. Etter fordampning av oppløsningsmidlet oppløses resten i ko-kende benzol (100 cm<3>) varm n-heptan (100 cm<3>) tilsettes, og oppløsningen las krystallisere. Krystallene skilles fra, vaskes med heptan og tørkes i vakuum. 3-etyl-indol-2-karboksylsyre-dimetylamid (22,5
g) oppnås således, sm.p. 154° C.
Eksempel 3: Ved å gå frem som i eksempel 2, men gå ut fra 3-etylindol-2-karboksylsyrehydra-zid (12,2 g) og monometylamin (50 g) oppnås 3-etylindol-2-karboksylsyre-monome-tylamid (8,5 g), sm. p. 186° C.
Eksempel 4: 3-etylindol-2-karboksylsyre (18,9 g) tilsettes i små porsjoner ved vanlig temperatur til en oppløsning av tionylklorid (13,1
g) i toluol (50 cm<3>). Blandingen røres ved 25° C i 30 minutter og oppvarmes derpå
langsomt til en temperatur på 76° C. En klar oppløsning oppnås, som kjøles til ca. + 5° C. Flytende dimetylamin (27 g) tilsettes derpå dråpevis, idet temperaturen holdes ved +5° C. Blandingen las henstå over
natt i kjøleskap. Det krystallinske produkt skilles fra, vaskes først med toluol og derpå med en stor mengde vann. Produktet tør-res, og 3-etylindol-2-karboksylsyre-dime-tylamid (16 g), sm. p. 152—153° C, oppnås således. Ved fordampning av toluoloppløs-ningene oppnås en annen felling (4 g), sm. p. 150—151° C. Etter omkrystallisering fra benzol oppnås et rent produkt (17 g), sm. p. 154° C.
Eksempel 5: Ved å gå frem som i eksempel 3, men erstatte monometylamin med ammoniakk (20 g), oppnås der 3-etylindol-2-karboksyl-syre-amid (5,6 g), sm. p. 134° C, fulgt av gjenstørkning og et annet smeltepunkt ved 140° C.
Claims (1)
- Fremgangsmåte for fremstilling av terapeutisk virksomme indolderivater, karakterisert ved at ammoniakk, et hydrazin eller mono- eller dimetylamin reageres med et syrehalogenid eller en ester eller azidet av 3-etylindol-2-karboksylsyre for å danne en forbindelse med formelen:i hvilken A betyr en enkelt binding eller en -NH-gruppe, og Ri og R2 er samme eller forskjellige og betyr vannstof f atomer eller metylgrupper.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72926968A | 1968-05-15 | 1968-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO123817B true NO123817B (no) | 1972-01-17 |
Family
ID=24930296
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO1966/69A NO123817B (no) | 1968-05-15 | 1969-05-13 |
Country Status (6)
| Country | Link |
|---|---|
| DE (1) | DE1923654A1 (no) |
| FR (1) | FR2008593A1 (no) |
| GB (1) | GB1269080A (no) |
| IE (1) | IE32687B1 (no) |
| NO (1) | NO123817B (no) |
| SE (1) | SE354344B (no) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8901594A (nl) * | 1989-06-23 | 1991-01-16 | Giemeta Luvema Bv | Ventilatie-inrichting. |
| BE1013930A3 (nl) * | 2001-01-24 | 2002-12-03 | Aralco Nv | Verbeterd verluchtingsrooster. |
-
1969
- 1969-04-18 GB GB09987/69A patent/GB1269080A/en not_active Expired
- 1969-04-25 IE IE571/69A patent/IE32687B1/xx unknown
- 1969-05-09 DE DE19691923654 patent/DE1923654A1/de active Pending
- 1969-05-13 NO NO1966/69A patent/NO123817B/no unknown
- 1969-05-14 FR FR6915717A patent/FR2008593A1/fr not_active Withdrawn
- 1969-05-14 SE SE06875/69A patent/SE354344B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE1923654A1 (de) | 1969-11-27 |
| FR2008593A1 (fr) | 1970-01-23 |
| IE32687L (en) | 1969-11-15 |
| GB1269080A (en) | 1972-03-29 |
| SE354344B (sv) | 1973-03-05 |
| IE32687B1 (en) | 1973-10-31 |
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