NO792301L - PROCEDURE FOR THE PREPARATION OF PROPIOPHENON DERIVATIVES - Google Patents
PROCEDURE FOR THE PREPARATION OF PROPIOPHENON DERIVATIVESInfo
- Publication number
- NO792301L NO792301L NO792301A NO792301A NO792301L NO 792301 L NO792301 L NO 792301L NO 792301 A NO792301 A NO 792301A NO 792301 A NO792301 A NO 792301A NO 792301 L NO792301 L NO 792301L
- Authority
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- Norway
- Prior art keywords
- preparation
- compounds
- derivatives
- propiophenon
- procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 6
- 238000002360 preparation method Methods 0.000 title claims abstract description 4
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical class CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 4
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 4
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 4
- 229960003147 reserpine Drugs 0.000 description 4
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 229960003054 gallamine Drugs 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- OZLPUNFFCJDMJD-UHFFFAOYSA-N 2-[2,3-bis[2-(triethylammonio)ethoxy]phenoxy]ethyl-triethylammonium Chemical compound CC[N+](CC)(CC)CCOC1=CC=CC(OCC[N+](CC)(CC)CC)=C1OCC[N+](CC)(CC)CC OZLPUNFFCJDMJD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 231100000569 acute exposure Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- REEUVFCVXKWOFE-UHFFFAOYSA-K gallamine triethiodide Chemical compound [I-].[I-].[I-].CC[N+](CC)(CC)CCOC1=CC=CC(OCC[N+](CC)(CC)CC)=C1OCC[N+](CC)(CC)CC REEUVFCVXKWOFE-UHFFFAOYSA-K 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
- 229940072358 xylocaine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/004—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with organometalhalides
-
- 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
- A61P25/24—Antidepressants
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Fremgangsmåte for fremstilling av propiofenon-derivater.Process for the preparation of propiophenone derivatives.
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for propio-fenonderivater med den generelle formel I The present invention relates to a process for propio-phenone derivatives with the general formula I
hvori, in which,
R^ står for et halogenatom, trifluormetyl eller trifluormetyltio, 1*2 står for hydrogenatom, et halogenatom, trif luormetyl eller trifluormetyltio, og ;R 3 atår for cyklobutyl eller tertbutyl, med unntagelse av forbindelser hvori = halogen, R2= H og R^= tertbutyl, ;samt farmaseutisk tålbare salter derav,;og det særegne ved fremgangsmåten i henhold til oppfinnelsen er at en forbindelse med formel II i. ; ; hvori R^og R2har den ovennevnte betydning, omsettes med en forbindelse med den generelle formel ;R3NH2, ;hvori R^ har den ovennevnte betydning, i et løsningsmiddel som f.eks. acetonitril med en temperatur på fra 0 til 25°C, ;og om ønsket overføres en erholdt forbindelse med formel (I> i et syreaddisjonssalt. ;Forbindelsene (II) fremstilles ved å gå ut fra nitriner; etter det følgende reaksjonsskjerna ; De følgende eksempler illustrerer oppfinnelsen.;Analyser og spektra IR og RMN har bekreftet strukturen av forbindelsen . ;Eksempel 1;m-trifluormetylc*-tertbutylamino-propiofenon og dets hydroklorid. R^ represents a halogen atom, trifluoromethyl or trifluoromethylthio, 1*2 represents a hydrogen atom, a halogen atom, trifluoromethyl or trifluoromethylthio, and ;R 3 represents cyclobutyl or tertbutyl, with the exception of compounds in which = halogen, R2 = H and R^ = tertbutyl, ;as well as pharmaceutically acceptable salts thereof,;and the peculiarity of the method according to the invention is that a compound of formula II in. ; ; in which R^ and R2 have the above-mentioned meaning, are reacted with a compound of the general formula ;R3NH2, ;in which R^ has the above-mentioned meaning, in a solvent such as e.g. acetonitrile with a temperature of from 0 to 25°C, and if desired, an obtained compound of formula (I) is transferred into an acid addition salt. The compounds (II) are prepared by starting from nitrines; after the following reaction core; The following examples illustrate the invention. Analyzes and spectra IR and RMN have confirmed the structure of the compound. Example 1 m-trifluoromethyl c*-tertbutylamino-propiophenone and its hydrochloride.
1. luormetYl-2E2Ei2f§D2D1. luormetYl-2E2Ei2f§D2D
1 en 1000 ml erlenmeyerkolbe med todelt holder, dråpetrakt på 100 ml, oppsigende kjøler (montert tørt og beskyttet ved hjelp av CaC^) innføres llg (0,452 mol) magnesiumspon og 30 ml vannfri eter. Man tilsetter en jodkrystall og innfører sakte en løsning av 61,5 g (0,564 mol) etylbromid. Etter avsluttet tilførsel oppvarmes i to timer ved tilbakeløpstemperaturen hvoretter det avkjøles på isblandet vannbad. Det innføres deretter sakte i kulden en oppløsning av 63,7 g (0,372 mol) metatrifluor-metylbenzohitril. Into a 1000 ml Erlenmeyer flask with two-piece holder, 100 ml dropping funnel, terminating condenser (mounted dry and protected by means of CaC^) is introduced 1lg (0.452 mol) magnesium shavings and 30 ml anhydrous ether. An iodine crystal is added and a solution of 61.5 g (0.564 mol) ethyl bromide is slowly introduced. After completion of the supply, it is heated for two hours at the return temperature, after which it is cooled in an ice-mixed water bath. A solution of 63.7 g (0.372 mol) metatrifluoromethylbenzohydryl is then introduced slowly in the cold.
Etter avsluttet tilsetning holdes blandingen på tilbakeløps-temperaturen i fire timer. Det avkjøles og hydrolyseres ved hjelp av 260 ml 2NHC1. Det dekanteres, eterfasen vaskes med vann, tørkes over MgSO^, inndampes til tørrhet og resten destilleres under vakuum. Kokepunkt 0,03=60 - 70°C. 2 • SY^E2lSi2£i^§t §Y_Hz£rif luormetYl-2-tertbutylamino-E£2Ei2^222<n>• After completion of the addition, the mixture is kept at the reflux temperature for four hours. It is cooled and hydrolysed with the aid of 260 ml of 2NHC1. It is decanted, the ether phase is washed with water, dried over MgSO 4 , evaporated to dryness and the residue is distilled under vacuum. Boiling point 0.03=60 - 70°C. 2 • SY^E2lSi2£i^§t §Y_Hz£rif luormetYl-2-tertbutylamino-E£2Ei2^222<n>•
Til en oppløsning av 19,8 g (0,09 8 mol) 3<1->trifluormetylpropio-fenon i 70 ml metylenklorid innføres dråpevis en løsning av 15,5 g (0,097 mol) brom i 25 ml metylenklorid. Det omrøres i 1 time og 30 minutter til avfarging av reaksjonsblandingen. Det inndampes til tørrhet ved omgivelsens temperatur hvoretter det to ganger avdampes 50 ml benzen. Det tilsettes' så 50 ml acetonitril og en liten mengde uoppløselig substans frafiltreres. Filtratet tilsettes deretter dråpevis til en oppløsning avkjølt på isblandet vann av 20,8 g tértfoutylamin i 60 ml acetonitril. Det omrøres deretter i fire timer ved 0°C og blandingen settes bort over natten. Det dannede bunnfall frafiltreres, vaskes med eter og filtratet inndampes til tørrhet. Resten opptas i eter. Uopp-løselig substans fra filtreres og eterløsningen vaskes med vann (to ganger). Det tørkes over MgSO^, filtreres og inndampes til tørrhet. Resten oppløses i 300 ml kokende petroleter og behandles, A solution of 15.5 g (0.097 mol) bromine in 25 ml methylene chloride is added dropwise to a solution of 19.8 g (0.098 mol) 3<1->trifluoromethylpropiophenone in 70 ml methylene chloride. It is stirred for 1 hour and 30 minutes to decolorize the reaction mixture. It is evaporated to dryness at ambient temperature, after which 50 ml of benzene are evaporated twice. 50 ml of acetonitrile is then added and a small amount of insoluble substance is filtered off. The filtrate is then added dropwise to a solution cooled in ice-mixed water of 20.8 g of tert-foutylamine in 60 ml of acetonitrile. It is then stirred for four hours at 0°C and the mixture is set aside overnight. The precipitate formed is filtered off, washed with ether and the filtrate is evaporated to dryness. The rest is taken up in ether. Insoluble substance from is filtered and the ether solution is washed with water (twice). It is dried over MgSO^, filtered and evaporated to dryness. The residue is dissolved in 300 ml of boiling petroleum ether and treated,
i 15 minutter med plantekull. Plantekullet avfiltreres og filtratet inndampes til tørrhet. for 15 minutes with charcoal. The charcoal is filtered off and the filtrate is evaporated to dryness.
Resten oppløses i aceton. Hydrokloridet utfelles ved tilsetning av et overskudd av saltsur eter. Det filtreres, av-suges på filter, vaskes med rikelig eter og deretter med aceton. The residue is dissolved in acetone. The hydrochloride is precipitated by the addition of an excess of hydrochloric acid ether. It is filtered, sucked off on a filter, washed with plenty of ether and then with acetone.
Det omkrystalliseres to ganger fra etanol.It is recrystallized twice from ethanol.
Smeltepunkt= 234°C (spalting)Melting point= 234°C (decomposition)
I den etterfølgende tabell - I\ ? er anført andre forbindelser fremstilt ved hjelp av den samme metode In the following table - I\ ? are listed other compounds prepared using the same method
Forbindelsene ble underkastet farmakologisk prøvning som The compounds were subjected to pharmacological testing which
viste deres psykotrope egenskaper.showed their psychotropic properties.
Giftigheten av forbindelsen ble bestemt med mus ved intraperitoneal tilførsel. LD 50 var omtrent 110-250 mg/kg. The toxicity of the compound was determined in mice by intraperitoneal administration. The LD 50 was approximately 110-250 mg/kg.
Man har videre studert innvirkning av forbindelsene på de ponto-genikulo-oksipitale punkter ved reserpinsyndrom i kurariserte katter, for å vise forbindelsenes anti-depressive egenskaper. The effects of the compounds on the ponto-geniculo-occipital points in reserpine syndrome in curarized cats have also been studied, in order to show the compounds' anti-depressant properties.
I katter, ble det påvist en spesifikk aktivitet i broområdet, sideknekjernen og oksipital korteks som benevnes ponto-genikulo-oksipitale punkter (P.G.O.).. In cats, a specific activity was detected in the pons area, the lateral geniculate nucleus and the occipital cortex, which are called ponto-geniculo-occipital points (P.G.O.).
Denne spontane aktivitet (punkter P.G.O.) som kommer til syneThis spontaneous activity (points P.G.O.) that comes into view
i våken-søvnsyklusen kan innføres med reserpin som er et farmakologisk middel som nedsetter innholdet av celebrale monoaminer. in the wake-sleep cycle can be introduced with reserpine, which is a pharmacological agent that reduces the content of cerebral monoamines.
Denne elektroensefalografiske aktivitet, modulert med nevron-mekanismer under kontroll av synaptiske nevrotransmitorer, ut-gjør da en farmakologisk test for studium av den sentrale virkning av medikamenter. This electroencephalographic activity, modulated by neuron mechanisms under the control of synaptic neurotransmitters, then constitutes a pharmacological test for studying the central action of drugs.
Alle forsøk ble gjennomført under akutt innvirkning på katterAll experiments were carried out under acute exposure to cats
av begge kjønn som veide 2-3 kg.of both sexes that weighed 2-3 kg.
Før den kirurgiske forberedelse som ble gjennomført under eter-narkose, fikk dyret en intraperitoneal injeksjon på 075 mg/kg i.p. reserpin. Before the surgical preparation, which was carried out under ether anesthesia, the animal received an intraperitoneal injection of 075 mg/kg i.p. reserpine.
Katten holdes i en beholder for å tillate kunstig åndedrett.The cat is kept in a container to allow artificial respiration.
Et lokalt bedøvelsesmiddel (2% xsylokain) injiseres ved trykk-punktene og innsnittene. A local anesthetic (2% xylocaine) is injected at the pressure points and incisions.
Det anbringes kanyler i femoral-venen for innføring av produktene og infusjon av et kurariserende middel, nemlig gallamin-trietjodid ("Flaksedil"), og femoral-arterien for å måle arterie-trykket. Monopolarelektroder er anordnet kortikalt og koaksiale bipolar-elektroder er anordnet stereotaksis i side-knekjernen. Cannulas are placed in the femoral vein for introducing the products and infusing a curative agent, namely gallamine triiodide ("Flaxedil"), and the femoral artery to measure the arterial pressure. Monopolar electrodes are arranged cortically and coaxial bipolar electrodes are arranged stereotaxically in the lateral knee nucleus.
Det kurariserte dyr gis kunstig åndedrett og holdes ved konstant temperatur under hele forsøket. The curarized animal is given artificial respiration and kept at a constant temperature throughout the experiment.
Elektroensefalogrammet, elektrokardiogrammet og arterie-trykket registreres ved hjelp av en polygraf av type Grass 79D. The electroencephalogram, electrocardiogram and arterial pressure are recorded using a Grass 79D polygraph.
Økende doser (0,1; 0,3; 1; 3; 10 og 30 mg/kg) av produktene som testes injiseres intravenøst med mellomrom 30 minutter, 4 timer og 30 minutter etter tilførsel av reserpinet. Increasing doses (0.1; 0.3; 1; 3; 10 and 30 mg/kg) of the products being tested are injected intravenously at intervals of 30 minutes, 4 hours and 30 minutes after administration of the reserpine.
Antallet punkter P.G.O. telles automatisk i perioder på 10 minutter og uttrykkes som prosentandel i forhold til perioder på 30 minutter idet verdien opnådd for 30 minutter tas som referanse (100%). The number of points P.G.O. is automatically counted in periods of 10 minutes and expressed as a percentage in relation to periods of 30 minutes, with the value obtained for 30 minutes being taken as a reference (100%).
Den effektive dose (DE 50) som reduserer antallet punkter P.G.O. med 50% beregnes ved hjelp av en halv-logaritmisk regresjonskurve. The effective dose (DE 50) that reduces the number of points P.G.O. with 50% is calculated using a semi-logarithmic regression curve.
Den effektive dose 50% av forbindelsene varierer fra 1,5 til 3 mg/kg idet forbindelsen nr. 2 (77 250) har vist seg mest aktiv. The effective dose of 50% of the compounds varies from 1.5 to 3 mg/kg, with compound No. 2 (77,250) proving to be the most active.
Resultatene av de foregående forsøk viser at forbindelsene harThe results of the previous experiments show that the compounds have
en innvirkning på det sentrale nervesystem og kan anvendes for behandling av depresjoner og dermed forbundne symtomer. an impact on the central nervous system and can be used to treat depression and associated symptoms.
Forbindelsene kan tilføres i hvilke som helst former egnet for oral, parenteral eller endorektal tilførsel, f.eks. i form av The compounds may be administered in any form suitable for oral, parenteral or endorectal administration, e.g. in the form of
tabletter, drageer, geler, spiselige eller injiserbare oppløsninger, etc, med vanlige passende tilsetningsmidler. tablets, dragees, gels, edible or injectable solutions, etc., with usual suitable additives.
Total dose utgjør 10 til 100 mg. Total dose amounts to 10 to 100 mg.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7820941A FR2430933A1 (en) | 1978-07-13 | 1978-07-13 | PROPIOPHENONE DERIVATIVES AND THEIR THERAPEUTIC APPLICATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO792301L true NO792301L (en) | 1980-01-15 |
Family
ID=9210717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO792301A NO792301L (en) | 1978-07-13 | 1979-07-11 | PROCEDURE FOR THE PREPARATION OF PROPIOPHENON DERIVATIVES |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0007843A1 (en) |
| JP (1) | JPS5522670A (en) |
| AU (1) | AU4890979A (en) |
| DK (1) | DK294379A (en) |
| FI (1) | FI792177A (en) |
| FR (1) | FR2430933A1 (en) |
| IL (1) | IL57780A0 (en) |
| NO (1) | NO792301L (en) |
| PT (1) | PT69912A (en) |
| ZA (1) | ZA793529B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2553408B1 (en) * | 1983-10-14 | 1986-11-28 | Lafon Labor | 1- (4-ACETYLAMINOPHENYL) -2-AMINO-PROPANONE DERIVATIVES, THEIR USE IN THERAPEUTICS AND THEIR PREPARATION PROCESS |
| IN182588B (en) * | 1998-05-12 | 1999-05-08 | Sun Pharmaceutical Ind Ltd | |
| EP2419400A1 (en) * | 2009-04-15 | 2012-02-22 | Research Triangle Institute | Monoamine reuptake inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3590M (en) * | 1963-08-08 | 1965-10-04 | Richardson Merrell Inc | Alpha- (dialkoylamino) trifluoromethylpropiophenones. |
| BE759838A (en) * | 1969-12-04 | 1971-06-03 | Wellcome Found | KETONES WITH BIOLOGICAL ACTIVITY |
-
1978
- 1978-07-13 FR FR7820941A patent/FR2430933A1/en active Granted
-
1979
- 1979-07-10 EP EP79400473A patent/EP0007843A1/en not_active Withdrawn
- 1979-07-11 FI FI792177A patent/FI792177A/en not_active Application Discontinuation
- 1979-07-11 NO NO792301A patent/NO792301L/en unknown
- 1979-07-12 IL IL57780A patent/IL57780A0/en unknown
- 1979-07-12 JP JP8918179A patent/JPS5522670A/en active Pending
- 1979-07-12 DK DK294379A patent/DK294379A/en unknown
- 1979-07-12 PT PT69912A patent/PT69912A/en unknown
- 1979-07-13 AU AU48909/79A patent/AU4890979A/en not_active Abandoned
- 1979-07-13 ZA ZA00793529A patent/ZA793529B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA793529B (en) | 1980-07-30 |
| JPS5522670A (en) | 1980-02-18 |
| FI792177A (en) | 1980-01-14 |
| PT69912A (en) | 1979-08-01 |
| FR2430933A1 (en) | 1980-02-08 |
| EP0007843A1 (en) | 1980-02-06 |
| IL57780A0 (en) | 1979-11-30 |
| FR2430933B1 (en) | 1980-12-05 |
| DK294379A (en) | 1980-01-14 |
| AU4890979A (en) | 1980-01-31 |
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