DK141529B - METHOD OF ANALOGUE FOR THE PREPARATION OF OR INCIDENTAL SALTS - Google Patents
METHOD OF ANALOGUE FOR THE PREPARATION OF OR INCIDENTAL SALTS Download PDFInfo
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- DK141529B DK141529B DK495076AA DK495076A DK141529B DK 141529 B DK141529 B DK 141529B DK 495076A A DK495076A A DK 495076AA DK 495076 A DK495076 A DK 495076A DK 141529 B DK141529 B DK 141529B
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- indole
- phenoxymethyl
- ethyl
- carbon atoms
- methyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
Description
141529 i141529 i
Den foreliggende opfindelse angår en analogifremgangsmåde til fremstilling af hidtil ukendte piperidinderivater af indol med den almene formel IThe present invention relates to an analogous process for the preparation of novel piperidine derivatives of indole of the general formula I
-Qi 0oC2 t * 1 2 hvori R og R betyder hydrogen eller en alkylgruppe med 3 5 1-4 carbonatomer, R betyder hydrogen, halogen, en alkyl gruppe med 1-4 carbonatomer eller en alkoxygruppe med 1-4 carbonatomer, og X betyder en ligekædet eller forgrenet alkylengruppe med 2-3 carbonatomer, eller salte deraf med farmakologisk acceptable syrer.Wherein R and R are hydrogen or an alkyl group of 1-4 carbon atoms, R is hydrogen, halogen, an alkyl group of 1-4 carbon atoms or an alkoxy group of 1-4 carbon atoms, and X is a straight or branched alkylene group having 2-3 carbon atoms, or salts thereof with pharmacologically acceptable acids.
12 3 10 Substituenterne R , R og R i betydningen en alkylgruppe kan være ligekædede eller forgrenede og indeholder 1-4 car- 3 bonatomer. R i betydningen en alkoxygruppe indeholder ligeledes 1-4 carbonatomer.12 3 10 The substituents R, R and R in the meaning of an alkyl group can be straight or branched chain and contain from 1 to 4 carbon atoms. R in the sense an alkoxy group also contains 1-4 carbon atoms.
Som halogenatomer kommer fluor, chlor og brom på tale.As halogen atoms, fluorine, chlorine and bromine come into play.
15 Eksempler på ligekædede og forgrenede hydrocarbongrupper med 2-3 carbonatomer, som betegnes med X, er ethylen, methylmethylen, propylen, dimethylmethylen og methylethylen, idet ethylen og propylen foretrækkes.Examples of straight and branched hydrocarbon groups having 2-3 carbon atoms denoted by X are ethylene, methylmethylene, propylene, dimethylmethylene and methylethylene, with ethylene and propylene being preferred.
De omhandlede forbindelser med den almene formel I samt de 20 farmakologisk acceptable salte deraf har antihypertensiv virkning.The present compounds of general formula I as well as the pharmacologically acceptable salts thereof have antihypertensive effect.
Forbindelserne har især vist sig effektive ved behandling af patienter med alvorlig eller vedvarende blodtrykforhøjelse, især diastolisk blodtryk. Forbindelserne er egnede 2 1A1529 til behandling af næsten alle former for stationære og fremskridende hypertensiv sygdom indbefattet den, ved hvilken blodtrykket er moderat forøget.In particular, the compounds have been shown to be effective in treating patients with severe or persistent hypertension, especially diastolic blood pressure. The compounds are suitable for treating almost all types of stationary and progressive hypertensive disease, including that at which blood pressure is moderately elevated.
De omhandlede forbindelser kan anvendes som sådanne eller 5 kan omdannes til salte med farmakologisk acceptable syrer.The present compounds may be used as such or may be converted into salts with pharmacologically acceptable acids.
De kan administreres oralt, som piller, tabletter, kapsler, pulvere og lignende. Den foretrukne form for oral administration er i form af en tablet indeholdende 10-300 mg aktiv forbindelse.They can be administered orally, such as pills, tablets, capsules, powders and the like. The preferred form of oral administration is in the form of a tablet containing 10-300 mg of active compound.
10 Forbindelsen kan også administreres parenteralt. Injektionsopløsninger indeholdende 50 mg/ml injektionsopløsning foretrækkes.The compound may also be administered parenterally. Injection solutions containing 50 mg / ml injection solution are preferred.
Doseringsprogrammet til blodtrykssænkning afhænger fuldstændig af patientens tilstand, patientens reaktion på 15 behandlingen samt hvorvidt eller ikke patienten skal be handles ambulant eller er hospitaliseret. Behandlingen bør begynde med små doser (100 mg) og forøges gradvis afhængigt af patientens reaktion. Doseringen kan forøges med intervaller på 5 til 7 dage, indtil en gennemsnitlig dags-20 dosis på 100 til 3QQ mg er nået. Til fortsættelse af behandlingen kræves sædvanligvis 2 til 4 doser om dagen.The dosing program for lowering blood pressure depends entirely on the patient's condition, the patient's response to the treatment, and whether or not the patient should be treated outpatient or hospitalized. Treatment should begin with small doses (100 mg) and gradually increase depending on the patient's reaction. Dosage may be increased at intervals of 5 to 7 days until an average daily dose of 100 to 3QQ mg is reached. To continue the treatment, usually 2 to 4 doses per day are required.
Til godtgørelse af effektiviteten af de ved fremgangsmåden ifølge opfindelsen fremstillede forbindelser til formindskelse af blodtrykket blev der udført en række forsøg som 25 følger.To demonstrate the effectiveness of the compounds of the present invention in reducing blood pressure, a number of experiments were performed as follows.
Der blev anvendt følgende prøvemetoder:The following test methods were used:
Forsøgsdyrene var rotter, hvori arterielle katedere var blevet implanteret i aorta ved en steril operation via lårarterien. Det var muligt at måle dyrenes blodtryk i 30 vågen tilstand direkte i blodet via en transducer (Statham 3 141529The test animals were rats in which arterial catheters had been implanted into the aorta by a sterile operation via the femoral artery. It was possible to measure the blood pressure of the animals in a waking state directly in the blood via a transducer (Statham 3 141529
Transducer Type TP 23 D 6) via en bærefrekvensmålende bro.Transducer Type TP 23 D 6) via a carrier frequency measuring bridge.
Dyrene blev behandlet ved administration af 10% almindeligt salt (natriumchlorid) i deres føde samt, begyndende med den 6. uge af deres levetid, ved hjælp af to indsprøjtnin-5 ger pr. uge af 5 mg ad gangen af ll-deoxycorticosteron= acetat pr. dyr, hvorved der udvikledes et forhøjet arterielt blodtryk beliggende mellem tallene 190 og 130 mm Hg. Forsøgsforbindelserne blev administreret til dyrene som følger:The animals were treated by administering 10% common salt (sodium chloride) in their food and, starting with the 6th week of their life, by two injections per day. per week of 5 mg at a time of II-deoxycorticosterone = acetate per animals, thereby developing an elevated arterial blood pressure located between the numbers 190 and 130 mm Hg. The test compounds were administered to the animals as follows:
Efter at blodtrykskontrolværdierne var blevet bestemt, blev 10 dyrene indgivet forsøgsforbindelsen peroralt suspenderet i 10 ml 1% methylcelluloseopløsning i den angivne dosering, og målinger blev foretaget 4 timer efter oral administration af forbindelsen.After the blood pressure control values were determined, the 10 animals were administered the test compound orally suspended in 10 ml of 1% methylcellulose solution at the indicated dosage and measurements were taken 4 hours after oral administration of the compound.
Resultaterne er angivet i den efterfølgende tabel. De i 15 tabellen anførte tal repræsenterer i hvert tilfælde middeltallet af mindst fem individuelle målinger af blodtryksformindskelsen (i mm HgJ pr. administreret forbindelse.The results are given in the following table. The figures given in the table in each case represent the mean of at least five individual measurements of the blood pressure decrease (in mm HgJ per compound administered).
4 161529 Påvirkning af det arterielle middelblodtryk med forskellige piperidino-alkylsubstituerede indolderivater hos hypertone rotter.4 161529 Influence of arterial mean blood pressure with various piperidino-alkyl-substituted indole derivatives in hypertonic rats.
Forbindelser: Forbindelserne blev indgivet som suspension i 1% methylcelluloseopløsning i 10 ml væske/kg gennem en spiserørssonde..Compounds: The compounds were administered as a suspension in 1% methylcellulose solution in 10 ml of liquid / kg through an esophageal probe.
Eksempel n Dosis Maksimal blodtrykssænkning (mg/kg) (mm Hg] 1__5 50__-55 ± 2_ 1 1 10 25 -38 ± 6 1 b TI 25 -25 + 7 1 d__9 25__-12 + 3_ 1 g 12 10__-28 + 5_ 1 f 12 25 -34 + 7 1 n__7 50__-27 ± 8_ 1 o 7 25 -48 ± lp_ 1 p__7 25__-33 t 5_ 1 k__7 50__-11 ± 8_ 1 a__6 50__- 4 ± 4_ 1 m 7 50 -8 + 5_ 1 c__7 25__- 5 ± 4_ 1 h 7 25__-14 t 6_ 1 i__7 25__-12 ± 4_ le 7 50__-12 + 7_ 1 j__7 50__-24 t 7_Example n Dose Maximum blood pressure drop (mg / kg) (mm Hg) 1__5 50 __- 55 ± 2_ 1 1 10 25 -38 ± 6 1 b TI 25 -25 + 7 1 d__9 25 __-12 + 3_ 1 g 12 10 __-28 + 5_ 1 f 12 25 -34 + 7 1 n__7 50 __- 27 ± 8_ 1 o 7 25 -48 ± lp_ 1 p__7 25 __- 33 t 5_ 1 k__7 50 __- 11 ± 8_ 1 a__6 50 __- 4 ± 4_ 1 m 7 50 - 8 + 5_ 1 c__7 25 __- 5 ± 4_ 1 h 7 25 __- 14 t 6_ 1 i__7 25 __- 12 ± 4_ le 7 50 __- 12 + 7_ 1 j__7 50 __- 24 t 7_
Kontrol: 1% methyl- _ o + o cellulose- opløsning α-methyl- g 15Q _33 + 5 lopa n betyder antallet af forsøgsdyr.Control: 1% methyl-o + o cellulose solution α-methyl-g 15Q _33 + 5 lopa n means the number of test animals.
De omhandlede forbindelser bevirker i forhold til kontroldyregruppen og i forhold til den med α-methyldopa behandlede gruppe forsøgsdyr en kraftig blodtrykssænkning, hvorved det skal tages i betragtning, at doseringen af a-methyldopa 5 141523 andrager mindst det 3-dobbelte af doseringen af de omhandlede forbindelser.The compounds of the present invention cause a significant drop in blood pressure relative to the control animal group and to the group treated with α-methyldopa, whereby it should be taken into account that the dosage of α-methyldopa 5 is at least 3 times the dose of the subject. compounds.
Fremgangsmåden ifølge opfindelsen er ejendommelig ved, at man omsætter et indolderivat med den almene formel IIThe process of the invention is characterized by reacting an indole derivative of the general formula II
αχ <m i r! 12αχ <m i r! 12
5 hvori R , R og X har den ovenfor anførte betydning, og Y betyder halogen eller en sulfonyloxygruppe,med et piperi= dinderivat med den almene formel IIIWherein R, R and X are as defined above and Y is halogen or a sulfonyloxy group having a piperidine derivative of the general formula III
bT).^ (iii) o hvori R har den ovenfor anførte betydning, eller et syreadditionssalt deraf, idet man om ønsket i det tilfælde, at 10 R·*" i formlen II betyder hydrogen, i tilslutning til kon densationen alkylerer indoInitrogenatornet med en alkylgrup-pe med 1-4 carbonatomer, og at reaktionsproduktet om ønsket overføres til et farmakologisk acceptabelt salt.(iii) wherein R is as defined above, or an acid addition salt thereof, wherein, if desired, in the case that R 10 in formula II means hydrogen, in addition to the condensation, the indo-nitrogen generator is alkylated with a alkyl group having 1-4 carbon atoms and, if desired, the reaction product is transferred to a pharmacologically acceptable salt.
Som reaktive grupper kommer chlor, brom, mesyloxy og tosyl= 15 oxy på tale.As reactive groups, chlorine, bromine, mesyloxy and tosyl = 15 oxy come into play.
Omsætningen af indolderivaterne II med forbindelserne III foregår hensigtsmæssigt i et opløsningsmiddel, såsom dio= xan, isopropanol eller Ν,Ν-dimethylformamid i nærværelse af en organisk eller uorganisk base, såsom N-ethyl-diiso= 20 propylamin, triethylamin eller kaliumcarbonat, eller i nærværelse af overskud af forbindelsen III, ved temperaturer mellem 20°C og tilbagesvalingstemperatur.The reaction of the indole derivatives II with the compounds III is conveniently carried out in a solvent such as dioxane, isopropanol or Ν, Ν-dimethylformamide in the presence of an organic or inorganic base such as N-ethyl diiso = propylamine, triethylamine or potassium carbonate, or in presence of excess compound III, at temperatures between 20 ° C and reflux temperature.
Forbindelserne med formlen II er enten kendte forbindelser 6 141529 eller kan let fremstilles ud fra kendte forbindelser ifølge trivielle metoder. Forbindelserne med formlen III er kendt fra tysk offentliggørelsesskrift nr. P 25 49 999.The compounds of formula II are either known compounds 6 or can be readily prepared from known compounds by trivial methods. The compounds of formula III are known from German Publication No. P 25 49 999.
Den efterfølgende indføring af substituenten i betydningen 5 en lavere alkylgruppe med 1-4 carbonatomer foregår ved omsætning af en forbindelse med den almene formel I, hvori = hydrogen, med et passende reaktivt alkylderivat (f.eks. alkyl= halogenid) ifølge kendte metoder.The subsequent introduction of the substituent within the meaning of a lower alkyl group of 1-4 carbon atoms takes place by reacting a compound of the general formula I, wherein = hydrogen, with a suitable reactive alkyl derivative (eg, alkyl = halide) according to known methods.
De farmakologisk acceptable salte opnår man på sædvanlig 10 måde, f.eks. ved neutralisation af forbindelserne I med ikke-toksiske uorganiske eller organiske syrer, såsom saltsyre, svovlsyre, phosphorsyre, hydrogenbromidsyre, eddikesyre, mælkesyre, citronsyre, æblesyre, salicylsyre, malon-syre, maleinsyre eller ravsyre.The pharmacologically acceptable salts are obtained in the usual manner, e.g. by neutralizing the compounds I with non-toxic inorganic or organic acids such as hydrochloric, sulfuric, phosphoric, hydrobromic, acetic, lactic, citric, malic, salicylic, malonic, maleic or succinic.
15 I de følgende eksempler beskrives fremgangsmåden ifølge opfindelsen nærmere.In the following examples, the method of the invention is described in more detail.
Eksempel 1 3-[2-(4-phenoxymethy1-piperidino)-ethyl]-indol.Example 1 3- [2- (4-Phenoxymethyl-piperidino) -ethyl] -indole.
En blanding af 8,96 g (0,04 mol) 3-(2-brom-ethyl)-indol, 20 7,65 g (0,04 mol) 4-phenoxymethyl-piperidin, 7,76 g (0,06 mol) N-ethyldiisopropylamin og 100 ml dioxan opvarmes i 9 timer til tilbagesvaling. Efter afkøling filtrerer man, inddamper filtratet i vakuum, optager resten i ether, vasker med vand, tørrer over natriumsulfat og inddamper.A mixture of 8.96 g (0.04 mole) of 3- (2-bromo-ethyl) -indole, 7.65 g (0.04 mole) of 4-phenoxymethyl-piperidine, 7.76 g (0.06 mole) N-Ethyl diisopropylamine and 100 ml dioxane are heated to reflux for 9 hours. After cooling, the filtrate is filtered, the filtrate is evaporated in vacuo, the residue is taken up in ether, washed with water, dried over sodium sulfate and evaporated.
25 Efter omkrystallisering fra isopropanol/ligroin opnår man 5,55 g 3-[2-(4-phenoxymethyl-piperidino)-ethyl]-indol (41% af teoretisk) med smeltepunkt 113-114°C.After recrystallization from isopropanol / ligroin, 5.55 g of 3- [2- (4-phenoxymethyl-piperidino) -ethyl] -indole (41% of theory) are obtained, mp 113-114 ° C.
Ud fra den isopropanoliske opløsning opnår man ved tilsætning af overskud af etherisk hydrogenchloridopløsning hy= 30 drochloridet med smeltepunkt 213°C.From the isopropanol solution, excess hydrochloric acid solution of hydrochloric acid, m.p. 213 °, is obtained by the addition of excess ethereal hydrogen chloride solution.
7 141529 På analog måde opnår man:7 141529 By analogy one obtains:
Betegnelse udbyt- Smeltepunkt °cDesignation yield - Melting point ° c
Eks. te % (opløsningsmiddel ......- —......— I. II . . — .1 '» - - 3—^ 2-[4-(2-brom-phenoxymethyl)-pipe= 101 - 102 la ridino]-ethylj-lndol ud fra 33 3-(2-brom-ethTl)-iadol og 4-(2-brom- (isopropenol) _phenoxymethyl j-piperidin __v * 3-|2-[4-(2-chlor-phenoxymethyl)-pipe= 113 - 114 lb ridino]-ethylj-indol ud fra 37 3-^ 2-[ 4- (3-chlor-phenoxymethyl)-pipe= 133 - 135 1° ridino]-ethylindol ud fra 51 3-^2-[4-(4-chlor-phenoxymethyl)-pipe= 141 - 142 ridino]-ethylindol ud fra 32 3-(2-brom-ethvl)-indol og 4-(4-chlor- (diethvlether _phenoxymethyl) -piperidin_;___laiew-iemer, 3-|2-[4-(2-fluor-phenoxymethyl)-pipe= 120 - 121 ridino]-ethylindol ud fra 48 3“(2-brom-ethvl)-indol og 4-(2-fluor- (eddikeester) _phenoxymethyl) -piperidin________ 3—^ 2-[4-(4-fluor-phenoxymethyl)-pipe= 130 - 131 lf ridino]-ethyl j-indol ud fra 36 _M^lu°r- _ (dlethylether; 3-| 2- [ 4- (2-methoxy-phenoxymethyl)- 107 - 108 lg piperidino]-ethylj—indol ud fra 32 3-^2-[4-(3-methoxy-phenoxymethyl)- 100 - 102 lh piperidino]-ethylindol ud fra 38 3~(2-brom-ethvl)-indol og 4-(3-methoxy- (eddikeester) _phenoxymethyl) -piperidin_,___2_ 3-^ 2-[4-(4-methoxy-phenoxymethyl)-pipe= 120 - 121 li ridino]-ethyl j— indol ud fra 44 3-(2-brom-ethvl)-indol og 4-(4-methoxy- (eddikeester) _{phenoxymethyl) -piperidin_.____]_|_J___ 8 U18-2«Ex. te% (solvent ......- --......- I. II. - .1 '' - - 3 ^ 2- [4- (2-bromo-phenoxymethyl) -pipe = 101 - [[102] Ridino] ethyl] -indole from 33 3- (2-bromo-ethyl) -iadole and 4- (2-bromo- (isopropenol) -phenoxymethyl] -piperidine) -3- 2- [4- (2) -chloro-phenoxymethyl) -pipe = 113 - 114 lb-ridino] -ethyl-indole from 37 3- ^ 2- [4- (3-chloro-phenoxymethyl) -pipe = 133-135-1-ridino] -ethylindole from 51 3- ^ 2- [4- (4-Chloro-phenoxymethyl) -pipe = 141 - 142-ridino] -ethylindole from 32 3- (2-bromo-ethyl) -indole and 4- (4-chloro- (diethyl ether) Phenoxymethyl) piperidine; 3-amide, 3- [2- [4- (2-fluoro-phenoxymethyl) -pipe = 120-112-ridino] -ethylindole from 48 3 ”(2-bromo-ethyl) -indole and 4 - (2-fluoro- (vinegar ester) -phenoxymethyl) -piperidine ________ 3- [2- (4- (4-fluoro-phenoxymethyl) -pipe = 130-131 lf ridino] -ethyl j-indole from 36 - ((ethyl ether; 3- [2- [4- (2-methoxy-phenoxymethyl) - 107 - 108 µg piperidino] ethyl] indole from 32 3- [2- (4- (3-methoxy-phenoxymethyl) - 100 - 102 lh piperidino] -ethylindole from 38 3 ~ (2-bromo-ethyl) -indole and 4- (3-methoxy- (vinegar ester) -phenoxymethyl) -piperidine-2-3- [2- (4- (4-methoxy-phenoxymethyl) -pipe = 120 - 121 l of Ridino] -ethyl] -indole from 44 3- (2-bromo-ethyl) -indole and 4- (4-methoxy- (vinegar ester) _ {phenoxymethyl) -piperidine _.____] _ | _J ___ 8 U18- 2 '
Betegnelse tidbyt- Smeltepunkt °CDesignation time-exchange Melting point ° C
Eks* ___te % (opløsninggnlddel) 3-^2-[4-(2-n-butoxy-phenoxymethyl)- 90-91 ^ piperidino] -ethyl j-indol ud fra 35 3-(2-brom-etIiyl)-indol og 4-(2-n- (eddikeester) _butoxy-phenoxymethyl )piperidin___j_ 3-|2-[4-(2-methyl-phenoxymethyl)- 102 - 103 piperidino]-ethyl j—indol ud fra 41 ^"(£"]?ro®“e^kyl) “indol (isopropanol)Ex.% (Dissolution portion) 3- [2- [4- (2-n-butoxy-phenoxymethyl) - 90-91] piperidino] -ethyl] -indole from 3- (2-bromo-ethyl) -indole and 4- (2-n- (acetic ester) -butoxy-phenoxymethyl) piperidine ___ j_ 3- [2- [4- (2-methyl-phenoxymethyl) - 102 - 103 piperidino] -ethyl] -indole from 41 ] indole (isopropanol)
_ methyl-phenoxymethyl) -pipendxn___v y J(methyl-phenoxymethyl) -pipendxn ___ v y J
3-"^ 2- [ 4- (3-methyl-phenoxymethyl) - 98 - 100 11 piperidino]-ethyl^-indol ud fra 32 3-ig-?rom-etHy1)-indol og 4-(3- (diethylether) _methyl-phenoxymethyl) -pipendxn_____“_' 3-^ 2-[4-(4-methyl-phenoxymethyl)- 130 - 132 lm piperidino]-ethyl j-indol ud fra 58 3-(2-brom-ethyl)-indol og 4-(4- _methyl-phenoxymethyl) -piperidin___(eddikeester) 1- methyl-3-[2-(4-phenoxymethyl-pipe= 89 - 90 ridino)-ethyl]-indol ud fra 43 ln l-methyl-3-(2-brom-ethyl)-indol og _4-phenoxymethyl-piperidin_;___(isopropanol) 2- methvl-3-[2-(4-phenoxymethyl-pipe= hydrochlorid ridino)-ethyl]-indol ud fra 45 214-216 2- methyl-3-(2-brom-ethyl)-indol og _4-phenoxymethyl-piperidin___(isopropanol) - 3-[3-(4-phenoxymethyl-piperidino)-pro= hydrochlorid lp pyl]-indol ud fra 43 222-224 3- (3-tosyloxy-propyl)-indol og 4-3- [2- (4- (3-Methyl-phenoxymethyl) - 98-100 11 piperidino] -ethyl] -indole from 32 3-pyrimethyl-ethylH-indole and 4- (3- (diethyl ether) 3- (2- (4-methyl-phenoxymethyl) - 130-132 lm piperidino] -ethyl] -indole from 58 3- (2-bromoethyl) - indole and 4- (4- (methyl-phenoxymethyl) -piperidine) (vinegar ester) 1- methyl-3- [2- (4-phenoxymethyl-pipe = 89-90-ridino) -ethyl] -indole from 43 ln-1-methyl- 3- (2-Bromo-ethyl) -indole and 4-phenoxymethyl-piperidine-2 (isopropanol) 2-methyl-3- [2- (4-phenoxymethyl-pipe = hydrochloride ridino) -ethyl] -indole starting from 45 214 -216 2- methyl-3- (2-bromo-ethyl) -indole and 4-phenoxymethyl-piperidine (isopropanol) - 3- [3- (4-phenoxymethyl-piperidino) -pro = hydrochloride 1-pyl] -indole 43 222-224 3- (3-tosyloxy-propyl) -indole and 4-
Iphenoxymethyl-piperidin (methanol)Iphenoxymethyl-piperidine (methanol)
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2550001 | 1975-11-07 | ||
| DE19752550001 DE2550001A1 (en) | 1975-11-07 | 1975-11-07 | NEW INDOL DERIVATIVES AND PROCESS FOR THEIR PRODUCTION |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK495076A DK495076A (en) | 1977-05-08 |
| DK141529B true DK141529B (en) | 1980-04-14 |
| DK141529C DK141529C (en) | 1980-09-01 |
Family
ID=5961169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK495076A DK141529C (en) | 1975-11-07 | 1976-11-02 | ANALOGY PROCEDURE FOR THE PREPARATION OF INCIDENTAL DERIVATIVES OR ITS SALES |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS5259164A (en) |
| AT (1) | AT352727B (en) |
| BE (1) | BE847975A (en) |
| CA (1) | CA1077941A (en) |
| DE (1) | DE2550001A1 (en) |
| DK (1) | DK141529C (en) |
| FI (1) | FI763150A (en) |
| FR (1) | FR2330396A1 (en) |
| GB (1) | GB1510765A (en) |
| IE (1) | IE43972B1 (en) |
| LU (1) | LU76143A1 (en) |
| NL (1) | NL7612288A (en) |
| SE (1) | SE7612236L (en) |
| SU (1) | SU628816A3 (en) |
| ZA (1) | ZA766379B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2905876A1 (en) | 1979-02-16 | 1980-08-28 | Boehringer Mannheim Gmbh | NEW PIPERIDINOPROPYL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS |
| US4327103A (en) * | 1980-07-07 | 1982-04-27 | Hoechst-Roussel Pharmaceuticals Incorporated | 3-{3-[4-(4-Fluorobenzoyl)piperidyl]propyl}-2-methyl indole |
-
1975
- 1975-11-07 DE DE19752550001 patent/DE2550001A1/en not_active Withdrawn
-
1976
- 1976-10-25 ZA ZA766379A patent/ZA766379B/en unknown
- 1976-10-28 CA CA264,610A patent/CA1077941A/en not_active Expired
- 1976-10-29 IE IE2396/76A patent/IE43972B1/en unknown
- 1976-11-02 SU SU762415646A patent/SU628816A3/en active
- 1976-11-02 DK DK495076A patent/DK141529C/en active
- 1976-11-03 SE SE7612236A patent/SE7612236L/en not_active Application Discontinuation
- 1976-11-03 FI FI763150A patent/FI763150A/fi not_active Application Discontinuation
- 1976-11-04 BE BE172070A patent/BE847975A/en unknown
- 1976-11-04 GB GB45918/76A patent/GB1510765A/en not_active Expired
- 1976-11-05 FR FR7633391A patent/FR2330396A1/en active Granted
- 1976-11-05 LU LU76143A patent/LU76143A1/xx unknown
- 1976-11-05 JP JP51133141A patent/JPS5259164A/en active Pending
- 1976-11-05 NL NL7612288A patent/NL7612288A/en not_active Application Discontinuation
- 1976-11-05 AT AT823976A patent/AT352727B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IE43972L (en) | 1977-05-07 |
| SE7612236L (en) | 1977-05-08 |
| DK141529C (en) | 1980-09-01 |
| ZA766379B (en) | 1977-10-26 |
| IE43972B1 (en) | 1981-07-15 |
| JPS5259164A (en) | 1977-05-16 |
| BE847975A (en) | 1977-05-04 |
| DE2550001A1 (en) | 1977-05-12 |
| GB1510765A (en) | 1978-05-17 |
| AT352727B (en) | 1979-10-10 |
| LU76143A1 (en) | 1977-05-18 |
| ATA823976A (en) | 1979-03-15 |
| FI763150A (en) | 1977-05-08 |
| CA1077941A (en) | 1980-05-20 |
| FR2330396A1 (en) | 1977-06-03 |
| DK495076A (en) | 1977-05-08 |
| SU628816A3 (en) | 1978-10-15 |
| NL7612288A (en) | 1977-05-10 |
| FR2330396B1 (en) | 1979-06-29 |
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