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DE2901362A1 - GUANIDE DERIVATIVES, THEIR PRODUCTION AND USE - Google Patents

GUANIDE DERIVATIVES, THEIR PRODUCTION AND USE

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Publication number
DE2901362A1
DE2901362A1 DE19792901362 DE2901362A DE2901362A1 DE 2901362 A1 DE2901362 A1 DE 2901362A1 DE 19792901362 DE19792901362 DE 19792901362 DE 2901362 A DE2901362 A DE 2901362A DE 2901362 A1 DE2901362 A1 DE 2901362A1
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formula
carbon atoms
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alkyl
hydrogen
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German (de)
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Peter Dr Neumann
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Sandoz AG
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Sandoz AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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 ring carbon atoms
    • C07D333/42—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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 ring carbon atoms with nitro or nitroso radicals directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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 ring carbon atoms
    • C07D333/28—Halogen atoms

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Furan Compounds (AREA)
  • Pyrrole Compounds (AREA)

Description

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Die Erfindung betrifft Guanidinderivate der Formel IThe invention relates to guanidine derivatives of the formula I

-R,-R,

ι 4 ι 4 CH0-CO-N=CCH 0 -CO-N = C ' "4'"4 *2^* 2 ^ ^R5^ R 5 Rl R l ^R6^ R 6 R3 R 3 ^R7^ R 7

worin R , R und R gleich oder verschieden sind und jeweils für Viasserstoff, Halogen oder Alkyl mit 1-4 Kohlenstoffatomen stehen, und entweder R4 und R unabhängig voneinander Wasserstoff,wherein R, R and R are the same or different and each represent hydrogen, halogen or alkyl with 1-4 carbon atoms, and either R 4 and R independently of one another are hydrogen,

Alkyl oder Hydroxyalkyl mit jeweils 1-4 Kohlenstoffatomen oder Alkoxyalkyl mit höchstens 6 Kohlenstoffatomen bedeuten, oder R. und R zusammen für Dimethylen oder Trimethylen stehen,Alkyl or hydroxyalkyl each with 1-4 carbon atoms or alkoxyalkyl with are at most 6 carbon atoms, or R. and R together for dimethylene or trimethylene stand,

R_ und R7 unabhängig voneinander WasserstoffR_ and R 7 independently of one another are hydrogen

oder Alkyl mit 1-4 Kohlenstoffatomen bedeuten, undor alkyl with 1-4 carbon atoms, and

X Schwefel, Sauerstoff, Imino oder Alkyliiaino mit 1-4 Kohlenstoffatomen bedeutet,X sulfur, oxygen, imino or alkyliiaino with 1-4 carbon atoms means

ihre Säureadditionssalze sowie ein Verfahren zu deren Herstellung.their acid addition salts and a process for their preparation.

Halogen bedeutet jeweils Fluor, Chlor, Brom oder Jod, vorzugsweise Chlor oder Brom. Alkyl besitzt vorzugsweise 1-3 Kohlenstoffatome, insbesondere 1 oder 2 Kohlenstoff atome. Hydroxyalkyl enthält vorzugsweise 2 oder 3 Kohlenstoffatome. Die Hydroxylgruppe steht vorzugsweise nicht an dem an das Stickstoffatom gebundeneHalogen in each case denotes fluorine, chlorine, bromine or iodine, preferably chlorine or bromine. Alkyl preferably has 1-3 carbon atoms, especially 1 or 2 carbon atoms. Hydroxyalkyl preferably contains 2 or 3 carbon atoms. The hydroxyl group preferably stands not bound to the nitrogen atom

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Kohlenstoffatom. Der Alkoxyrest im Alkoxyalkyl befindet sich vorzugsweise in Endstellung der Alkylenkette, die vorzugsweise 2 oder 3 Kohlenstoffatome, insbesondere Kohlenstoffatome besitzt. Der Alkoxyrest im Alkoxyalkyl steht vorzugsweise für Methoxy.Carbon atom. The alkoxy radical is located in the alkoxyalkyl preferably in the end position of the alkylene chain, which preferably has 2 or 3 carbon atoms, in particular Has carbon atoms. The alkoxy radical in alkoxyalkyl is preferably methoxy.

R steht vorzugsweise für Halogen. R_ steht vorzugsweise für Halogen. X bedeutet zweckmässigerweise Schwefel oder Sauerstoff, vorzugsweise Schwefel.R preferably represents halogen. R_ is preferably for halogen. X is conveniently sulfur or Oxygen, preferably sulfur.

Erfindungsgemäss gelangt man zu Verbindungen der Fortnel I, indem man Verbindungen der Formel II,According to the invention one arrives at compounds of the Fortnel I by adding compounds of the formula II,

CH_COYCH_COY

λ II λ II

worin R1, R , R_ und X obige Bedeutung besitzen, und Ywherein R 1 , R, R_ and X have the above meaning, and Y

X £m «JX £ m «J

einen abspaltbaren Rest bedeutet, mit Verbindungen der Formel III,denotes a removable radical, with compounds of the formula III,

/ 5/ 5

HN=C ° IIIHN = C ° III

worin R., R5, R und R_ obige Bedeutung besitzen, umsetzt, und die erhaltenen Verbindungen der Formel Iin which R., R 5 , R and R_ have the above meaning, reacted, and the compounds of the formula I obtained

gegebenenfalls in ihre Säureadditionssalze überführt.optionally converted into their acid addition salts.

Das Verfahren kann in einer für die Herstellung analoger Ν,Ν,Ν-substituierter Guanidinderivate bekannten Weise durchgeführt werden. Y steht z.B. für Hydroxy, Alkoxy mit 1-4 Kohlenstoffatomen, Chlor oder Brom.The process can be carried out in a manner known for the preparation of analogous Ν, Ν, Ν-substituted guanidine derivatives be performed. Y stands for example for hydroxy, alkoxy with 1-4 carbon atoms, chlorine or bromine.

909830/0 668909830/0 668

BADBATH

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23013622301362

Die Ausgangsverbindungen der Formel II sind entweder bekannt oder nach an sich bekannten Verfahren herstellbar. Die Thienylessigsäuren können erhalten werden, indem man z.B. 2- bzw. 3-Methy!thiophene in 2- bzw. 3-Brommethylthiophene überführt und aus diesen über die 2- bzw. 3-Thienylacetonitrile die 2- bzw. 3-Thienylessigsäuren herstellt.The starting compounds of the formula II are either known or can be prepared by processes known per se. The thienylacetic acids can be obtained by converting, for example, 2- or 3-methylthiophenes into 2- or 3-bromomethylthiophenes and using the 2- or 3-thienylacetonitriles to prepare the 2- or 3-thienylacetic acids.

Die Verbindungen der Formel I können in an sich bekannter Weise in ihre Säureadditionssalze übergeführt werden und umgekehrt. Als Säuren sind z.B. Maleinsäure, Oxalsäure oder Chlorwasserstoffsäure geeignet.The compounds of the formula I can be known per se Way to be converted into their acid addition salts and vice versa. The acids are e.g. maleic acid, Oxalic acid or hydrochloric acid are suitable.

Die Verbindungen der Formel I zeichnen sich durch günstige pharmakodynamische Eigenschaften aus. Sie wirken insbesondere antihypertensiv.The compounds of the formula I are distinguished by favorable pharmacodynamic properties. they seem especially antihypertensive.

Die Verbindungen der Formel I können ebenfalls in Form ihrer pharmazeutisch verträglichen Säureadditionssalze verabreicht werden, die den gleichen Grad an Aktivität besitzen wie die freien Basen.The compounds of the formula I can also be used in the form of their pharmaceutically acceptable acid addition salts administered that have the same level of activity as the free bases.

Die Erfindung umfasst pharmazeutische Zubereitungen, die Verbindungen der Formel I in Form der freien Basen oder in Form pharmazeutisch verträglicher Säureaddi™ tionssalze zusammen mit pharmazeutisch verwendbaren Träger- oder Verdünnungsmitteln enthalten. Sie können in an sich bekannter Weise hergestellt werden und liegen z„B» als Tabletten oder Kapseln vor.The invention encompasses pharmaceutical preparations, the compounds of the formula I in the form of the free bases or in the form of pharmaceutically acceptable acid addition salts together with pharmaceutically acceptable ones Contain carriers or diluents. They can be produced and located in a manner known per se z “B” as tablets or capsules.

In den nachfolgenden Beispielen sind die Temperaturen in Grad-Celsius angegeben und sind unkorrigiert„In the following examples, the temperatures are given in degrees Celsius and are uncorrected "

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In der Tabelle werden folgende Bezeichnungen verwendet:The following terms are used in the table:

1) freie Base, falls nicht anders angegeben1) free base, unless otherwise stated

2) Zersetzung2) decomposition

3) Hydrochlorid3) hydrochloride

4) R4 + R6 = -CH2-CH2-4) R 4 + R 6 = -CH 2 -CH 2 -

Beispiel 1: (2,4-Dichlor-3-thienyl)acetyl-guanidin Example 1: (2,4- dichloro-3- thienyl) acetylguanidine

Eine Lösung von 3 g Guanidin in 80 ml Isopropanol wird mit einer Lösung von 10 g (2,4-Dichlor-3-thienyl)essigsUuremethylester in 10 ml Isopropanol versetzt und 15 Stunden bei Zimmertemperatur gerührt. Das Reaktionsgemisch wird daraufhin eingedampft. Der Rückstand wird zwischen 2N wässeriger Chlorwasserstoffsäure und Aether verteilt, die wässerige Phase mit wässeriger Ammoniaklösung basisch gestellt und anschliessend mit Essigester extrahiert. Die Essigesterlösung wird weitgehend eingeengt, bis die Titelverbindung vom Smp. 215-223° (Zers.) auskristallisiert.A solution of 3 g of guanidine in 80 ml of isopropanol becomes with a solution of 10 g (2,4-dichloro-3-thienyl) ethyl acetate added in 10 ml of isopropanol and stirred for 15 hours at room temperature. The reaction mixture is then evaporated. The residue is between 2N aqueous hydrochloric acid and ether distributed, the aqueous phase made basic with aqueous ammonia solution and then with ethyl acetate extracted. The ethyl acetate solution is largely concentrated until the title compound has a melting point of 215-223 ° (decomp.) crystallized out.

Zu dem als Ausgangsverbindung verwendeten (2,4-Dichlor-3-thienyl)essigsäuremethylester kann man wie folgt gelangen: To the (2,4-dichloro-3-thienyl) acetic acid methyl ester used as the starting compound can be reached as follows:

a)a)

Ein Gemisch von 25 g 2,4-Dibrom-3-methylthiophen, 29 g Kupfer(I) Chlorid und 75 ml Dimethylformamid wird 20 Stunden lang unter Stickstoff zum Rückfluss erhitzt. Das erkaltete Gemisch wird in 750 ml Wasser gegossenA mixture of 25 g of 2, 4-dibromo-3-methylthiophene, 29 g of copper (I) chloride and 75 ml of dimethylformamide is heated for 20 hours under nitrogen to reflux. The cooled mixture is poured into 750 ml of water

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und einer Wasserdampfdestillation unterworfen. Die organische Phase wird abgetrennt, getrocknet und destilliert, wobei man die Titelverbindung als farbloses OeI erhält.and subjected to steam distillation. The organic Phase is separated off, dried and distilled, the title compound being obtained as a colorless oil.

b)b)

9,4 g 2,4-Dichlor-3-methylthiophen, 10 g N-Bromsuccinimid und 50 rag α,α'-Azoisobutyronitril und 100 ml Tetrachlorkohlenstoff werden zusammen 15 Stunden land zum Rückfluss erhitzt. Das Gemisch wird filtriert, das Filtrat wird ein gedampft. Der ölige Rückstand wird destilliert, wobei man die Titelverbindung erhält.9.4 g of 2,4-dichloro-3-methylthiophene, 10 g of N-bromosuccinimide and 50 ml of α, α'-azoisobutyronitrile and 100 ml of carbon tetrachloride are refluxed together for 15 hours. The mixture is filtered, the filtrate is concentrated steamed. The oily residue is distilled to give the title compound.

c) (2jt4-Dichlor-3-thienYl]^acetonitrilc) (2 jt 4-dichloro-3-thienYl] ^ acetonitrile

9,6 g 2,4-Dichlor-3-brommethylthiophen werden in 160 ml Aethanol gelöst und mit einer Lösung von 5,8 g Kaliumcyanid in 50 ml Wasser versetzt. Das Gemisch wird 30 Minuten lang auf 65° erhitzt und gerührt. Danach wird rasch abgekühlt, 50 ml Wasser dazugegeben und mit Methylenchlorid extrahiert. Die organische Phase wird mit Aktivkohle behandelt, getrocknet und eingedampft. Der Rückstand wird destilliert, wobei man (2,4-Dichlor-3-thienyl)acetonitril erhält.9.6 g of 2,4-dichloro-3-bromomethylthiophene are added to 160 ml Dissolved ethanol and a solution of 5.8 g of potassium cyanide added in 50 ml of water. The mixture is heated to 65 ° for 30 minutes and stirred. After that, will cooled rapidly, added 50 ml of water and extracted with methylene chloride. The organic phase is with Treated activated charcoal, dried and evaporated. The residue is distilled, using (2,4-dichloro-3-thienyl) acetonitrile receives.

5,4 g (2,4-Dichlor-3-thienyl)acetonitril, 8 ml Eisessig, 5 ml Wasser und 5 ml konz. Schwefelsäure werden zusammen 3 Stunden lang zum Rückfluss erhitzt. Das Reaktionsgemisch wird mit etwas Eiswasser verdünnt. Der entstandene Niederschlag wird abfiltriert und in verdünnter wässriger Ammoniaklösung gelöst. Die Lösung wird mit Aktiv-Kohle behandelt, filtriert und mit verdünnter Schwefelsäure angesäuert, wobei man die Titelverbindung erhält.5.4 g (2,4-dichloro-3-thienyl) acetonitrile, 8 ml glacial acetic acid, 5 ml water and 5 ml conc. Sulfuric acid are refluxed together for 3 hours. The reaction mixture is diluted with a little ice water. The resulting precipitate is filtered off and dissolved in dilute aqueous ammonia solution. The solution is treated with activated charcoal , filtered and acidified with dilute sulfuric acid to give the title compound.

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5,2 g (2f4-Dichlor-3-thienyl)essigsäure, 40 ml Methanol und 0,8 ml konz. Schwefelsäure werden zusammen 5 Stunden lang zürn Rückfluss erhitzt. Das Re akt ions gemisch wird dann eingedampft und der Rückstand mit 25 g Eis versetzt. Dieses Gemisch wird mit Methylenchlorid extrahiert. Die organische Phase wird mit wässriger Ammoniaklösung gewaschen, getrocknet und eingedampft, wobei man den (2,4-Dichlor-3-thienyl)essigsäuremethylester erhält.5.2 g (2 f 4-dichloro-3-thienyl) acetic acid, 40 ml of methanol and 0.8 ml of conc. Sulfuric acid are refluxed together for 5 hours. The reaction mixture is then evaporated and 25 g of ice are added to the residue. This mixture is extracted with methylene chloride. The organic phase is washed with aqueous ammonia solution, dried and evaporated to give methyl (2,4-dichloro-3-thienyl) acetic acid.

Beispiel 2:Example 2:

Analog Beispiel 1 gelangt man zu folgenden Verbindungen der Formel I, worin X Schwefel bedeutet und der Acetylguanidinrest in der durch "y" angegebenen Stellung steht;Analogously to Example 1, the following compounds of the formula I are obtained, in which X is sulfur and the acetylguanidine radical is in the position indicated by "y";

Beispielexample BrBr ClCl R3 R 3 R4 R 4 HH R6 R 6 *7* 7 yy Smp. °M.p. ° CC. aa ClCl BrBr HH HH HH HH HH 33 215-220215-220 2)2) bb BrBr BrBr HH HH HH HH HH 33 217-230217-230 CC. ClCl ClCl HH HH HH HH HH 33 212-220212-220 2)2) dd CH3 CH 3 HH ClCl HH HH HH HH 33 199-201199-201 ee BrBr ClCl CH3 CH 3 HH HH HH HH 33 158-162158-162 ff ClCl ClCl HH HH HH HH HH 22 167-175°167-175 ° gG BrBr BrBr HH HH HH HH HH 22 159-169°159-169 ° hH CH3 CH 3 BrBr HH HH HH H-H- HH 22 199-209°199-209 ° 3)3) ii HH ClCl CH3 CH 3 HH HH HH HH 33 195-205°195-205 ° yy QiQi ClCl ClCl HH HH HH HH 33 kk ÖL·OIL· HH HH HH 33

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Beispielexample Ri R i R2 R 2 R3 R 3 R4 R 4 R5 R 5 R6 R 6 R7 R 7 y Smp. ° C J y m.p. ° C J 11 HH BrBr ClCl HH HH HH HH 33 mm CH3 CH 3 ClCl HH HH HH HH HH 33 ηη CH3 CH 3 CH3 CH 3 HH HH HH HH HH 33 οο FF. ClCl HH HH HH HH HH 33 PP. FF. BrBr HH HH HH HH HH 33 qq ClCl FF. HH HH HH HH HH 33 rr BrBr FF. HH HH HH HH HH 33 SS. FF. FF. HH HH HH HH HH 33 tt BrBr ClCl HH CH3 CH 3 HH HH HH 33 UU ClCl ClCl HH CH3 CH 3 HH HH HH 33 VV BrBr ClCl HH CH3 CH 3 HH CH3 CH 3 HH 33 WW. BrBr ClCl HH [CH2I3OH[CH 2 I 3 OH HH HH HH 33 XX ClCl ClCl HH [CH2I3OCH[CH 2 I 3 OCH 3H 3 H. HH HH 33 yy ClCl ClCl HH 4)4) HH 4)4) HH 33 ZZ FF. ClCl HH 4)4) HH 4)4) HH 33

3700/IG/SE SANDOZ-PATENT-GMBH3700 / IG / SE SANDOZ-PATENT-GMBH

909830/0668909830/0668

Claims (1)

2üüi3622üüi362 Sandoz-Patent-GribH
LorrachSandoz Patent GribH
Lorrach Guanidinderivate, ihre Herstellung und VerwendungGuanidine derivatives, their manufacture and use PatentansprücheClaims 1. Guanidinderivate der Formel I,1. guanidine derivatives of the formula I, R3 R 3 j ^j ^ CH2 CH 2 -CO-N=C-CO-N = C ^R6^ R 6 ΊΊ ^X^^ X ^ Ri R i ^R7^ R 7
worin R , R und R gleich oder verschieden sind undwherein R, R and R are the same or different and jeweils für Wasserstoff, Halogen oder Alkyl rait 1-4 Kohlenstoff atomen stehen, und entweder R und R unabhängig voneinander Wasserstoff,each represent hydrogen, halogen or alkyl having 1-4 carbon atoms, and either R and R independently of one another are hydrogen, Alkyl oder Hydroxyalkyl mit jeweils 1-4 Kohlenstoffatomen oder Alkoxyalkyl mitAlkyl or hydroxyalkyl each with 1-4 carbon atoms or alkoxyalkyl with höchstens 6 Kohlenstoffatomen bedeuten, oder R. und R^ zusammen für Dimethylen oder Tri™mean a maximum of 6 carbon atoms, or R. and R ^ together for dimethylene or Tri ™ methylen stehen,methylene stand, R und R unabhängig voneinander Wasserstoff oder Alkyl rait 1-4 Kohlenstoffatomen bedeuR and R independently of one another are hydrogen or alkyl has 1-4 carbon atoms ten , und
X Schwefel, Sauerstoff, Imino oder Alkyliminoth, and
X sulfur, oxygen, imino or alkylimino mit 1-4 Kohlenstoffatomen bedeutet, und ihre Säureadditionssalze„with 1-4 carbon atoms, and their acid addition salts " π;"; η 8 3 n/0868 BAD ORIG/NALπ; "; η 8 3 n / 0868 BAD ORIG / NAL - 2 - 500-5467- 2 - 500-5467 2, Verfahren zur Herstellung von Verbindungen der Formel I, dadurch gekennzeichnet, dass man Verbindungen der Formel II,2, a process for the preparation of compounds of the formula I, characterized in that compounds of formula II, IIII v;orin R1, R , R, und X obige Bedeutung besitzen und Y einen abspaltbaren Rest bedeutet, mit Verbindungen der Formel III,v; orin R 1 , R, R, and X have the above meaning and Y is a removable radical, with compounds of the formula III, R5
HN=C III R 5
HN = C III worin R., R_, R, und R obige Bedeutung besitzen, umsetzt, und die erhaltenen Verbindungen der Formel I gegebenenfalls in ihre Säureadditionssalze überführt. in which R., R_, R, and R have the above meanings, and the compounds of the formula I obtained are optionally converted into their acid addition salts. 3. Heilmittel, gekennzeichnet durch einen Gehalt an Verbindungen der Formel I.3. Medicinal products, characterized by a content of compounds of the formula I. 909830/0668
BAD ORIGINAL909830/0668
BATH ORIGINAL
DE19792901362 1978-01-25 1979-01-15 GUANIDE DERIVATIVES, THEIR PRODUCTION AND USE Withdrawn DE2901362A1 (en)

Applications Claiming Priority (1)

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CH79978 1978-01-25

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AU (1) AU4359279A (en)
BE (1) BE873658A (en)
DE (1) DE2901362A1 (en)
FR (1) FR2415636A1 (en)
GB (1) GB2013192A (en)
IE (1) IE790126L (en)
IL (1) IL56486A0 (en)
IT (1) IT7947732A0 (en)
NL (1) NL7900444A (en)
SE (1) SE7900459L (en)
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MXPA06014792A (en) 2004-06-16 2007-02-16 Wyeth Corp Diphenylimidazopyrimidine and -imidazole amines as inhibitors of b-secretase.
DE602005017033D1 (en) 2004-06-16 2009-11-19 Wyeth Corp AMINO-5,5-DIPHENYLIMIDAZOLONE DERIVATIVES FOR BETA SEKRETASE INHIBITION
CA2593515A1 (en) 2005-01-14 2006-07-20 Wyeth Amino-imidazolones for the inhibition of beta-secretase
RU2007124935A (en) 2005-02-01 2009-03-10 Вайет (Us) AMINOPYRIDINES AS β-SECTRETASIS INHIBITORS
JP2008530103A (en) 2005-02-14 2008-08-07 ワイス Azolylacylguanidines as beta-secretase inhibitors
WO2006088694A1 (en) 2005-02-14 2006-08-24 Wyeth SUBSTITUTED THIENYL AND FURYL ACYLGUANIDINES AS β-SECRETASE MODULATORS
MX2008000212A (en) 2005-06-30 2008-03-24 Wyeth Corp Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for beta-secretase modulation.
TW200738683A (en) 2005-06-30 2007-10-16 Wyeth Corp Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation
KR20080050430A (en) 2005-09-26 2008-06-05 와이어쓰 Amino-5- [4- (difluoromethoxy) phenyl] -5-phenylimidazolone compounds as beta-secretase (CAC) inhibitors
WO2007100536A1 (en) 2006-02-24 2007-09-07 Wyeth DIHYDROSPIRO[DIBENZO[A,D][7]ANNULENE-5,4'-IMIDAZOL] COMPOUNDS FOR THE INHIBITION OF β-SECRETASE
US7700606B2 (en) 2006-08-17 2010-04-20 Wyeth Llc Imidazole amines as inhibitors of β-secretase
AR065814A1 (en) 2007-03-23 2009-07-01 Wyeth Corp DERIVATIVES OF 5-PHENYLIMIDAZOLONE, INHIBITORS OF BETA-SECRETASA, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND USES TO PREVENT AND / OR TREAT ASSOCIATED DISORDERS AT LEVELS BETA-AMYLOOES ELEVATED.

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NL7900444A (en) 1979-07-27
SE7900459L (en) 1979-07-26
IL56486A0 (en) 1979-03-12
GB2013192A (en) 1979-08-08
BE873658A (en) 1979-07-23
IT7947732A0 (en) 1979-01-23
ZA79315B (en) 1980-09-24
FR2415636A1 (en) 1979-08-24
JPS54112859A (en) 1979-09-04
IE790126L (en) 1979-07-25

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