DE2525656A1 - PROCESS FOR PRODUCING NEW HETEROCYCLIC COMPOUNDS - Google Patents
PROCESS FOR PRODUCING NEW HETEROCYCLIC COMPOUNDSInfo
- Publication number
- DE2525656A1 DE2525656A1 DE19752525656 DE2525656A DE2525656A1 DE 2525656 A1 DE2525656 A1 DE 2525656A1 DE 19752525656 DE19752525656 DE 19752525656 DE 2525656 A DE2525656 A DE 2525656A DE 2525656 A1 DE2525656 A1 DE 2525656A1
- Authority
- DE
- Germany
- Prior art keywords
- fluorenone
- formula
- addition salts
- acid addition
- propoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
- C07D203/10—Radicals substituted by singly bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
SANDOZ-PATENT-GmbH. Case 100-41S9SANDOZ PATENT GmbH. Case 100-41S9
L ο r r a c hL ο r r a c h
Verfahren zur Herstellung neuer heterocyclischer VerbindungenProcess for the preparation of new heterocyclic links
Die Erfindung betrifft ein Verfahren zur Herstellung neuer heterocyclischer Verbindungen der Formel I, worinThe invention relates to a method of manufacture new heterocyclic compounds of the formula I, in which
Het einen 2-Indolinonrest, der in 4-,5-,6- oder 7-Stellung des Indolinongerüstes mit der Seitenkette verbunden ist, oder einen 9-Fluorenonrest, der in 1-, 2-, 3- oder 4-Stellung des Fluorenongerüstes mit der Seitenkette verbunden ist, bedeutet undHet a 2-indolinone residue in 4-, 5-, 6- or 7-position of the indolinone skeleton is connected to the side chain, or a 9-fluorenone residue, which is connected to the side chain in the 1-, 2-, 3- or 4-position of the fluorenone skeleton, means and
R für die Gruppe A,B,C oder D steht, worin ηR represents the group A, B, C or D, in which η
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die Zahl 2 oder 3, η1 die Zahl 1,2,3 oder 4 und X-X1 Aethylen oder Vinylen bedeuten, wobei gegebenenfalls in der Gruppe D die beiden dem N-Atom benachbarten C-Atome durch je eine oder je zwei Alky!gruppen mit 1-4 Kohlenstoffatomen substituiert sind und ihrer Säureadditionssalze, sowie auch die Verbindungen der Formel I und ihre Säureadditionssalze. the number 2 or 3, η 1 the number 1, 2, 3 or 4 and XX 1 denotes ethylene or vinylene, where in group D the two carbon atoms adjacent to the nitrogen atom are each replaced by one or two alkyl groups are substituted by 1-4 carbon atoms and their acid addition salts, as well as the compounds of the formula I and their acid addition salts.
Steht Het für einen 2-Indolinon- oder einen 9-Fluorenonrest, so bedeutet dieser vorzugsweise 2-Indolinon-4-yl bzw. 9-Fluorenon-4-yl.If Het stands for a 2-indolinone or a 9-fluorenone residue, this preferably means 2-indolinon-4-yl or 9-fluorenon-4-yl.
Steht R für die Gruppe C1 so bedeutet X-X' vorzugsweise Aethylen.If R stands for the group C 1 , XX 'is preferably ethylene.
Steht R für die Gruppe D, so bedeutet n1 vorzugsweise 3 oder 4 und sind die dem N-Atom benachbarten C-Atome vorzugsweise alkyliert, insbesondere dialkyliert. Diese Alkylsubstituenten enthalten vorzugsweise 1 oder 2, Insbesondere 1 Kohlenstoffatom. If R stands for the group D, then n 1 is preferably 3 or 4 and the C atoms adjacent to the N atom are preferably alkylated, in particular dialkylated. These alkyl substituents preferably contain 1 or 2, in particular 1, carbon atom.
Der Rest R steht bevorzugt für eine tertiäre Aminogruppierung, deren Stickstoffatom mit verzweigten Kohlenstoffatomen verknüpft ist, wxe beispielsweise einem 2,2,5,5-Tetramethylpyrrolidinyl- oder 2,2,6,6-Tetramethylpiperidino-Rest.The radical R preferably represents a tertiary amino group, whose nitrogen atom with branched Carbon atoms is linked, for example a 2,2,5,5-tetramethylpyrrolidinyl or 2,2,6,6-tetramethylpiperidino radical.
Erfindungsgemäss gelangt man zu den neuen Verbindun-According to the invention one arrives at the new compounds
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gen der Formel I und ihren Säureadditionssalzen, indem man eine Verbindung der Formel Ha oder Hb, worin Y für den Säurerest eines reaktionsfähigen Esters steht, mit einer Verbindung der Formel III,gene of the formula I and their acid addition salts by adding a compound of the formula Ha or Hb, where Y is the acid residue of a reactive Esters stands with a compound of the formula III,
worin R obige Bedeutung besitzt, umsetzt und die Verbindungen der Formel I in Form der Basen oder als Säureadditionssalze gewinnt.in which R has the above meaning, and the compounds of the formula I are converted in the form of bases or wins as acid addition salts.
Aus den freien Basen lassen sich in bekannter Weise Säureadditionssalze gewinnen und umgekehrt.Acid addition salts can be obtained from the free bases in a known manner and vice versa.
Die Umsetzung einer Verbindung der Formel Ha oder Hb mit einer Verbindung der Formel III kann analog zu für die Herstellung bekannter 3-Amino-2-hydroxyprepoxy-Verbindungen beschriebenen Methoden erfolgen. Y steht in der Formel Hb insbesondere für Halogen, vorzugsweise Chlor oder Brom, oder eine Gruppe R_-SO2-O-, worin R2 Phenyl, To-IyI oder niederes Alkyl bedeutet. Die Umsetzung wird vorzugsweise in einem unter den Reaktionsbedingungen inerten organischen Lösungsmittel, z.B. in einem cyclischen oder offenkettigen Aether wie Dioxan oder Diäthylenglykoldimethyläther durchgeführt. Gegebenenfalls verwendet man als Lösungsmittel die Verbindung der Formel III imThe reaction of a compound of the formula Ha or Hb with a compound of the formula III can be carried out analogously to the methods described for the preparation of known 3-amino-2-hydroxyprepoxy compounds. In the formula Hb, Y stands in particular for halogen, preferably chlorine or bromine, or a group R_-SO 2 -O-, in which R 2 is phenyl, To-IyI or lower alkyl. The reaction is preferably carried out in an organic solvent which is inert under the reaction conditions, for example in a cyclic or open-chain ether such as dioxane or diethylene glycol dimethyl ether. If appropriate, the compound of the formula III is used as the solvent
Ueberschuss. Man kann auch dieExcess. You can also do that
Umsetzung in der Schmelze durchführen. Die Reaktionstemperatur liegt zweckmässig zwischen etwa Raumtemperatur und 200°. Die Reaktionsdauer ist u.a. von der Reaktionstemperatur abhängig.Implementation in the melt. The reaction temperature is expediently between about Room temperature and 200 °. The reaction time depends, among other things, on the reaction temperature.
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Aus dem Reaktionsgemisch können die Verbindungen der Formel I nach bekannten Methoden isoliert und gereinigt werden.The compounds of the formula I can be isolated from the reaction mixture by known methods and cleaned.
Die Ausgangsverbihdungen der Formel Ha und Hb sind bekannt oder analog zu bekannten Methoden, ausgehend vom entsprechenden Hydroxyoxindol bzw. Hydroxyfluoren-9-on, herstellbar.The starting compounds of the formula Ha and Hb are known or analogous to known methods, starting from the corresponding hydroxyoxindole or Hydroxyfluoren-9-one, preparable.
Die Verbindungen der Formel III sind bekannt.The compounds of the formula III are known.
Soweit die Herstellung der benötigten Ausgangsmaterialien nicht beschrieben wird, sind diese bekannt oder nach an sich bekannten Verfahren bzw. analog zu den hier beschriebenen oder analog zu an sich bekannten Verfahren herstellbar.As far as the production of the required starting materials is not described, these are known or by methods known per se or analogously to those described here or analogously can be produced by methods known per se.
Die Verbindungen der Formel I und ihre pharmakologisch verträglichen Säureadditionssalze sind in der Literatur bisher nicht beschrieben. Sie weisen im Tierversuch interessante pharmakodynämische Eigenschaften auf und können daher als Heilmittel verwendet werden. ■The compounds of formula I and their pharmacological Compatible acid addition salts have not yet been described in the literature. You wise pharmacodynamic of interest in animal experiments Properties and can therefore be used as a remedy. ■
Insbesondere zeigen die neuen Verbindungen antiarrhythmische Wirkung, wie an Mäusen mit Chloroform-Arrhythmie (Methode von Lawson, J.W., J.Pharmac. exp.Ther. 160 [1968], 22-31) festgestellt werden konnte. Sie sind aufgrund dieser Wirkung zur Behandlung von Herzrhythmusstörungen, wieIn particular, the new compounds show antiarrhythmic action, as was found in mice with chloroform arrhythmia (method by Lawson, JW, J. Pharmac. Exp. Ther. 160 [1968], 22-31). Because of this effect, they are used to treat irregular heartbeats, such as
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z.B. Herzflimmern, geeignet. Die Tagesdosis liegt bei etwa 5 bis 400 mgj diese Dosis kann nötigenfalls in 2 bis 4 Anteilen oder auch als Retardform verabreicht werden.e.g. fibrillation, suitable. The daily dose is At around 5 to 400 mgj this dose can be used if necessary can be administered in 2 to 4 portions or as a sustained release form.
Bevorzugte Vertreter dieser Verbindungsklasse sind die Verbindungen der Formel Ia, worinPreferred representatives of this class of compounds are the compounds of the formula Ia, in which
Het einen in 4-Stellung mit der Seitenkette verbundenen 2-Indolinonrest oder einen in 4-Stellung mit der Seitenkette verbundenen 9-Fluorenonrest bedeutet,Het one connected to the side chain in the 4-position 2-indolinone radical or one in the 4-position means 9-fluorenone residue connected to the side chain,
n" für die Zahl 1 oder 2 undn "for the number 1 or 2 and
R für Alkyl mit 1-4 Kohlenstoffatomen stehen,R stands for alkyl with 1-4 carbon atoms,
und ihre Säureadditionssalze.and their acid addition salts.
Als Heilmittel können die Verbindungen der Formel I bzw. ihre physiologisch verträglichen Säureadditionssalze allein oder in geeigneter Arzneiform verabreicht werden.The compounds of the formula I or their physiologically acceptable acid addition salts can be used as medicaments be administered alone or in a suitable dosage form.
Die Erfindung betrifft auch Heilmittel, die eine Verbindung der Formel I in freier Form oder in Form ihrer physiologisch verträglichen Additionssalze mit Säuren enthalten. Diese Heilmittel, beispielsweise eine Lösung oder eine Tablette, können nach bekannten Methoden, unter Verwendung der üblichen Hilfs- und Trägerstoffe, hergestellt werden.The invention also relates to medicaments which contain a compound of the formula I in free form or in In the form of their physiologically compatible addition salts with acids. These remedies for example a solution or a tablet can be made using known methods the usual auxiliary and carrier materials will.
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26256562625656
„ 6 _ 100-4189 "6 _ 100-4189
In den nachfolgenden Beispielen, welche die Erfindung näher erläutern, erfolgen alle Temperaturangaben in Celsiusgraden.In the following examples, which explain the invention in more detail, all temperatures are given in degrees Celsius.
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Eeispiel 1: lzi2iHvdroxv-3-_(2z2x5z5-tetrame- Example 1: lzi2iHvdroxv-3 -_ (2 z 2 x 5 z 5-tetrame-
ΪΙϊΥ^ΐ1ΐ2Σϊ!£2ΐϊ^1ί2Υΐΐ2Ε2Ε2ϊίΥΐζ2ζ fluorenonΪΙϊΥ ^ ΐ1ΐ2Σϊ! £ 2ΐϊ ^ 1ί2Υΐΐ2Ε2Ε2ϊίΥΐζ2ζ fluorenone
4 g 4-(2,3-Epoxypropoxy)-9-fluorenon werden zusammen mit 4 g 2,2,5,5-Tetramethylpyrrolidin in 30 ml Dioxan 15 Stunden im Autoklaven auf 150° erhitzt. Nach dem Abkühlen wird die Reaktionsinischung eingedampft. Der Rückstand wird in Aether aufgenommen und mit 2 N Salzsäure ausgezogen. Die wässrige Lösung wird alkalisch gestellt und mit Methylenchlorid erschöpfend extrahiert. Die Methylenchloridphase wird eingedampft und der Rückstand aus Essigsäureäthylester/Petroläther kristallisiert? Smp. der Titelverbindung: 137-139°.4 g of 4- (2,3-epoxypropoxy) -9-fluorenone are combined with 4 g of 2,2,5,5-tetramethylpyrrolidine in 30 ml of dioxane heated to 150 ° in an autoclave for 15 hours. After cooling, the reaction mixture becomes evaporated. The residue is taken up in ether and extracted with 2N hydrochloric acid. the aqueous solution is made alkaline and extracted exhaustively with methylene chloride. The methylene chloride phase is evaporated and the residue crystallized from ethyl acetate / petroleum ether? M.p. of the title compound: 137-139 °.
4 g 4-(2,3-Epoxypropoxy)-9-fluorenon werden mit 15 ml Aethylenimin über Nacht bei Raumtemperatur stehen gelassen. Das überschüssige Aethylenimin wird abgedampft, der Rückstand in Aether aufgenommen und die Lösung bis zur beginnenden Kristallisation eingedampft. . . Smp. der Titelverbindung: 113 - 116°.4 g of 4- (2,3-epoxypropoxy) -9-fluorenone are mixed with 15 ml of ethyleneimine left to stand at room temperature overnight. The excess ethyleneimine is evaporated, the residue taken up in ether and the solution until the beginning of crystallization evaporated. . . M.p. of the title compound: 113-116 °.
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Beispiel 3 : 4-_[2-HvdrgxY^ 3-jl_£_2-dih^dro-2::imi-_ Example 3 : 4 -_ [2-HvdrgxY ^ 3-jl_ £ _2-dih ^ dro-2 :: imi-_
renonrenon
5 g 4- (2,3-Epoxypropoxy) -9--f luorenon und 3,8 g 2-Araino-pyrimidin werden 30 Minuten auf 100°C erhitzt. Die Schmelze wird in Essigester aufgenommen und mit 2 η Salzsäure ausgezogen. Das als Harz ausgefallene Hydrochlorid wird alkalisch gestellt und mit Methylenchlorid extrahiert. Das Lösungsmittel wird verdampft und der Rückstand aus Aethanol kristallisiert (Smp. 178 - 179°C) .5 g of 4- (2,3-epoxypropoxy) -9 - fluorenone and 3.8 g of 2-araino-pyrimidine are heated to 100 ° C for 30 minutes. The melt is taken up in ethyl acetate and extracted with 2 η hydrochloric acid. The hydrochloride precipitated as resin is made alkaline and extracted with methylene chloride. The solvent is evaporated and the residue crystallized from ethanol (melting point 178-179 ° C.).
In analoger Weise erhält man ausgehend von den entsprechenden Ausgangsverbindungen der Formeln Ha bzw. Hb, worin Y Chlor bedeutet, und III folgende Verbindungen der Formel I:In an analogous manner, starting from the corresponding starting compounds of the formulas, one obtains Ha or Hb, where Y is chlorine, and III the following compounds of the formula I:
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Nr.E.g.
No.
ZU
Bsp.Nr.Analogue
TO
Example No.
der Seiten
kette am He-
terocyclusposition
of the sides
chain on he-
terocyclus
piperidino2,2,6,6-tetramethyl
piperidino
pyrrolidinyl2,2,5,5-tetramethyl-1-
pyrrolidinyl
peridino2,2,6,6-tetramethylpi-
peridino
pyrrolidinyl2,2,5,5-tetramethyl-1-
pyrrolidinyl
yi9-azabicyclo [3.3.1] non-9-
yi
yi9-azabicyclo L3.3.1] non-9-
yi
pyridyl1,2-dihydro-2-imino-l-
pyridyl
pyrrolidinyl2,2,5,5-tetramethyl-1-
pyrrolidinyl
HClHCl
HydrochloridHydrochloride
cncn cncn TiTi
Cn O UD CD OOCn O UD CD OO coco
O IO 00O IO 00 coco
I-' O I- ' O
•Cfc• Cfc
cn cn cn cn
cncn
CDCD
- li 100-4189 - li 100-4189
OHOH
Het-O-CH -CH-CH -RHet-O-CH-CH-CH -R
OH
Het^O-CH -CH-CH -N, -CH,OH
Het ^ O-CH -CH-CH -N, -CH,
c — /\c - / \
R1R1 IaR 1 R 1 Ia
NHNH
-N (CH-)-N (CH-)
X1 X 1
Het-O-CH2-CH-CH2 Het-O-CH 2 -CH-CH 2
Ha OHHa OH
Het-O-CH2-CH-CH2Y HbHet-O-CH 2 -CH-CH 2 Y Hb
H-R IIIH-R III
509883/0983509883/0983
Claims (9)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH838174A CH602710A5 (en) | 1974-06-19 | 1974-06-19 | Substd. 9-fluorenone and 2-indolinone derivs |
| CH838074A CH599160A5 (en) | 1974-06-19 | 1974-06-19 | Substd. 9-fluorenone and 2-indolinone derivs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2525656A1 true DE2525656A1 (en) | 1976-01-15 |
Family
ID=25703229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752525656 Pending DE2525656A1 (en) | 1974-06-19 | 1975-06-09 | PROCESS FOR PRODUCING NEW HETEROCYCLIC COMPOUNDS |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS51125060A (en) |
| AT (1) | ATA466375A (en) |
| AU (1) | AU8216875A (en) |
| CA (1) | CA1036163A (en) |
| DD (1) | DD118086A5 (en) |
| DE (1) | DE2525656A1 (en) |
| DK (1) | DK259475A (en) |
| ES (1) | ES438637A1 (en) |
| FI (1) | FI751727A (en) |
| FR (1) | FR2275200A1 (en) |
| GB (1) | GB1500063A (en) |
| HU (1) | HU169926B (en) |
| IE (1) | IE41562B1 (en) |
| IL (1) | IL47503A0 (en) |
| NL (1) | NL7507131A (en) |
| NO (1) | NO752078L (en) |
| SE (1) | SE7506757L (en) |
| SU (1) | SU583755A3 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2960178D1 (en) * | 1978-06-06 | 1981-04-09 | Hoechst Ag | New substituted phenylpiperazine derivatives, pharmaceutical compositions containing them and process for their preparation |
| NZ529822A (en) | 1999-01-22 | 2005-11-25 | Elan Pharm Inc | Acyl derivatives which treat VLA-4 related disorders |
| TW200307671A (en) | 2002-05-24 | 2003-12-16 | Elan Pharm Inc | Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins |
| TWI281470B (en) | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
| DE602006019296D1 (en) | 2005-09-29 | 2011-02-10 | Elan Pharm Inc | PYRIMIDINYLAMIDE COMPOUNDS INHIBITING THE LEUKOCYTE ADHESION MEDIATED BY VLA-4 |
| EP1940827B1 (en) | 2005-09-29 | 2011-03-16 | Elan Pharmaceuticals Inc. | Carbamate compounds which inhibit leukocyte adhesion mediated by vla-4 |
| EA017110B1 (en) | 2006-02-27 | 2012-09-28 | Элан Фамэсьютикэлс, Инк. | PYRIMIDINYLSULFONAMIDE COMPOUNDS (VARIANTS), METHOD FOR PREPARING SAME (VARIANTS), PHARMACEUTICAL COMPOSITION, METHOD FOR TREATING A DISEASE MEDIATED BY α4 INTEGRIN, METHOD FOR REDUCING AND/OR PREVENTING AN INFLAMMATORY COMPONENT OF A DISEASE OR AN AUTOIMMUNE RESPONSE |
| CN102459179A (en) | 2009-04-27 | 2012-05-16 | 艾伦药物公司 | Pyridinone antagonists of alpha-4 integrins |
-
1975
- 1975-06-09 DE DE19752525656 patent/DE2525656A1/en active Pending
- 1975-06-10 FI FI751727A patent/FI751727A/fi unknown
- 1975-06-10 DK DK259475A patent/DK259475A/en unknown
- 1975-06-11 NO NO752078A patent/NO752078L/no unknown
- 1975-06-12 SE SE7506757A patent/SE7506757L/en unknown
- 1975-06-16 GB GB25530/75A patent/GB1500063A/en not_active Expired
- 1975-06-16 NL NL7507131A patent/NL7507131A/en not_active Application Discontinuation
- 1975-06-17 AU AU82168/75A patent/AU8216875A/en not_active Expired
- 1975-06-17 ES ES438637A patent/ES438637A1/en not_active Expired
- 1975-06-17 DD DD186699A patent/DD118086A5/xx unknown
- 1975-06-17 FR FR7518882A patent/FR2275200A1/en active Granted
- 1975-06-17 IE IE1359/75A patent/IE41562B1/en unknown
- 1975-06-17 HU HUSA2805A patent/HU169926B/hu unknown
- 1975-06-17 IL IL47503A patent/IL47503A0/en unknown
- 1975-06-18 AT AT466375A patent/ATA466375A/en not_active Application Discontinuation
- 1975-06-18 JP JP50073280A patent/JPS51125060A/en active Pending
- 1975-06-18 CA CA229,607A patent/CA1036163A/en not_active Expired
- 1975-06-19 SU SU7502145931A patent/SU583755A3/en active
Also Published As
| Publication number | Publication date |
|---|---|
| DD118086A5 (en) | 1976-02-12 |
| FR2275200B1 (en) | 1979-06-08 |
| SE7506757L (en) | 1975-12-22 |
| SU583755A3 (en) | 1977-12-05 |
| IE41562L (en) | 1975-12-19 |
| FR2275200A1 (en) | 1976-01-16 |
| NL7507131A (en) | 1975-12-23 |
| IE41562B1 (en) | 1980-01-30 |
| JPS51125060A (en) | 1976-11-01 |
| ATA466375A (en) | 1979-08-15 |
| IL47503A0 (en) | 1975-08-31 |
| GB1500063A (en) | 1978-02-08 |
| ES438637A1 (en) | 1977-06-01 |
| DK259475A (en) | 1975-12-20 |
| NO752078L (en) | 1975-12-22 |
| FI751727A (en) | 1975-12-20 |
| AU8216875A (en) | 1976-12-23 |
| CA1036163A (en) | 1978-08-08 |
| HU169926B (en) | 1977-02-28 |
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