CH547801A - 4 and 7-Aminopropoyx-oxindole derivs - useful as anti-arrhythmics and beta-adrenergic blockers - Google Patents
4 and 7-Aminopropoyx-oxindole derivs - useful as anti-arrhythmics and beta-adrenergic blockersInfo
- Publication number
- CH547801A CH547801A CH924871A CH924871A CH547801A CH 547801 A CH547801 A CH 547801A CH 924871 A CH924871 A CH 924871A CH 924871 A CH924871 A CH 924871A CH 547801 A CH547801 A CH 547801A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- oxindole
- alkyl
- compound
- compounds
- Prior art date
Links
- 230000003288 anthiarrhythmic effect Effects 0.000 title description 2
- 239000003416 antiarrhythmic agent Substances 0.000 title 1
- 239000002876 beta blocker Substances 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- QPBYYTKPYJRYKF-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)-1,3-dihydroindol-2-one Chemical compound N1C(=O)CC2=C1C=CC=C2OCC1CO1 QPBYYTKPYJRYKF-UHFFFAOYSA-N 0.000 claims description 4
- -1 2-methyl- butyn-2-ylamino Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000005623 oxindoles Chemical class 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 1
- GGSPVXOWJFDKLJ-UHFFFAOYSA-N ethyl 2-[[2-hydroxy-3-[(2-oxo-1,3-dihydroindol-4-yl)oxy]propyl]amino]-2-methylpropanoate Chemical compound C(C)OC(C(C)(NCC(COC1=C2CC(NC2=CC=C1)=O)O)C)=O GGSPVXOWJFDKLJ-UHFFFAOYSA-N 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 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 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 abstract 2
- 125000006193 alkinyl group Chemical group 0.000 abstract 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 238000005984 hydrogenation reaction Methods 0.000 abstract 1
- 125000003884 phenylalkyl group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- FTJQLPXJRKHATE-UHFFFAOYSA-N 4-hydroxy-1,3-dihydroindol-2-one Chemical class OC1=CC=CC2=C1CC(=O)N2 FTJQLPXJRKHATE-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- VUGCBIWQHSRQBZ-UHFFFAOYSA-N 2-methylbut-3-yn-2-amine Chemical compound CC(C)(N)C#C VUGCBIWQHSRQBZ-UHFFFAOYSA-N 0.000 description 2
- ANIZZDHCSZULKA-UHFFFAOYSA-N 4-hydroxy-1-methyl-3h-indol-2-one Chemical compound C1=CC=C(O)C2=C1N(C)C(=O)C2 ANIZZDHCSZULKA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000001834 epinephrinelike Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 206010042431 subvalvular aortic stenosis Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
Title cpds of formula (I): (where R1=H or 1. alkyl, X=OCH2CH (OR3)CH2NHR2 in 4- or 7- posn, R2=alkyl, cycloalkyl, alkoxyalkyl with >=2C atoms sepg O and N, phenylalkyl opt substd. by alkyl, or O alkyl with >=2C atoms sepg Ph and N, alkinyl, or carbalkoxyalkyl, and R3=H or COA where A is alkyl, 1. alkylcycloalkyl or a 5-6 membered oxyheterocyclic residue) are prepd by condensing the corresp. epoxypropoxy, substd cpds with H2NR2, or with an N-benzylamine followed by hydrogenation.
Description
Die Erfindung hat ein Verfahren zur Herstellung neuer Oxindole der Formel 1, worin Rl für Wasserstoff oder einen niederen Alkylrest steht und R2 einen Alkinylrest, dessen Dreifachbindung nicht in x,3-Stellung steht zum Stickstoffatom. woran der Alkinylrest gebunden ist oder einen Carbalkoxyalkylrest bedeutet und ihrer Säureadditionssalze zum Gegen', tattl.
Steht 9, für niederes Alkyl, so enthält dieser Alkylrest insbesondere 1 bis 4. vorzugsweise 1 Kohlenstoffatom.
Stellt R2 eine Alkinylgruppe dar, so enthält diese insbesondere 3 bis 7 Kohlenstoffatome. Eine bevorzugte Gruppe dieser Reihe ist 1,1 -Dimethyl-2-propinyl.
Stellt R.. eine Carbalkoxyalkylgruppe dar, so enthält deren Alkoxyrest insbesondere 1 bis 4, vorzugsweise 1 oder 2 Kohlenstoffatome und deren Alkylrest insbesondere 1 bis 6 Kohlenstoffatome.
Besonders bevorzugt sind Verbindungen in denen Rl Wasserstoff bedeutet und worin R2 am a-Kohlenstoffatom verzweigt ist.
Erfindungsgemäss gelangt man zu den Oxindolen der Formel I und ihren Säureadditionssalzen, indem man Verbindungen der Formel II, worin R, obige Bedeutung besitzt, mit Aminen der Formel III, worin R2 obige Bedeutung besitzt, umsetzt, und die so erhaltenen Verbindungen der Formel I als freie Basen oder als Säureadditionssalze gewinnt.
Aus den freien Basen lassen sich in bekannter Weise Säureadditionssalze herstellen und umgekehrt.
Die Umsetzung der Verbindungen der Formel II mit Aminen der Formel III kann nach bekannten Methoden erfolgen und wird beispielsweise in einem unter den Reaktionsbedingungen inerten organischen Lösungsmittel, z.B. in einem aromatischen Kohlenwasserstoff wie Benzol, Toluol, Xylol, in einem cyclischen Äther wie Dioxan, Tetrahydrofuran, in Amylalkohol durchgeführt.
Die Reaktionstemperatur kann zwischen 20 und 1500 liegen: im allgemeinen arbeitet man vorzugsweise bei Siedetemperatur des Reaktionsgemisches am Rückfluss. Die Reaktionsdauer ist von der Reaktionstemperatur abhängig.
Die nach dem obigen Verfahren hergestellten Verbindungen der Formel I können nach bekannten Methoden aufgearbeitet und gereinigt werden.
Die Verbindungen detu pe,- FSîe IrIrSn z.B. durch Umsetzung der Natriumsalze der entsprechenden 4-Hydroxyoxindole der Formel IV, worin R1 obige Bedeutung besitzt, mit Epibromhydrin in Dimethylsulfoxyd als Lösungsmittel erhalten werden.
Nach Beendigung der Reaktion giesst man in Wasser und extrahiert mit Essigester. Die Essigesterextrakte werden bis zur Kristallisation des Epoxypropoxyindols eingeengt.
Von den Verbindungen der Formel IV sind 4-Hydroxyoxindol und 4-Hydroxy-l methyloxindol bekannt. Die neuen Verbindungen der Formel IV können, wie 4-Hydroxy-l-methyloxindol, z.B. durch Cyclisierung der entsprechenden N -Alkyl-N-chloroacetyl.o-anisidine und Dimethylierung (Ätherspaltung) der so erhaltenen 1 -Alkyl-4-methoxyoxindolen hergestellt werden,
Soweit die Herstellung der Ausgangsverbindungen nicht beschrieben ist, sind diese bekannt oder analog zu bekannten Methoden herzustellen.
Die neuen Verbindungen der Formel I und ihre pharmakologisch verträglichen Säureadditionssalze besitzen bei geringer Toxizität interessante pharmakodynamische Eigenschaften und können daher als Heilmittel verwendet werden,
Die neuen Substanzen zeigen am spontanschlagenden isolierten Meerschweinchenvorhof eine Hemmung der positivinotropen Adrenalinwirkung und führen am narkotisierten Ganztier (Katze, Hund) zu einer starken Hemmung der durch Isoproterenol [1(3 ,4-Dihydroxyphenyl)-2-isopropylamino- äthanols bedingten Tachycardie und Blutdrucksenkung.
Die Verbindungen besitzen demnach eine Blockerwirkung auf die adrenergenen 3-Rezeptoren, und können daher u.a. zur Prophylaxe und Therapie von Koronarerkrankungen, insbesondere zur Behandlung von Angina pectoris, zur Behandlung des hyperkinetischen Herzsyndroms und der aus einer muskulär-hypertrophen, subvalvulären Aortenstenose resultierenden Zustände eingesetzt werden.
Aufgrund ihrer antiarrhythmischen Wirkungen sind die Verbindungen ausserdem zur Behandlung von Herzrhythmusstörungen geeignet.
Die zu verwendenden Dosen variieren naturgemäss je nach der Art der verwendeten Substanz, der Administration und des zu behandelnden Zustandes.
In den nachfolgenden Beispielen, welche die Erfindung näher erläutern, ihren Umfang jedoch in keiner Weise einschränken sollen, erfolgen alle Temperaturangaben in Cel siusgraden und sind unkorrigiert.
EMI1.1
Beispiel I
4-[2-h ydroxy-3-(2-methyl-3-butin-2-ylamino)- propoxyl]-oxindol
3 g 4-(2,3-Epoxypropoxy)oxindol, 9 g 3-Amino-3-methylbutin und 40 ml Tetrahydrofuran werden 2 Tage unter Rühren zum Sieden erhitzt. Man filtriert die heisse Lösung und lässt kristallisieren. Die Titelverbindung schmilzt von 172 bis 174".
Das als Ausgangsmaterial verwendete 4-(2,3-Epoxypropoxy)-oxindol wurde wie folgt hergestellt:
273 g 4-Hydroxyoxindol, 1300 ml Dimethylsulfoxyd und 55,8 g 80%iges Natriumhydrid werden 1 /2 Stunden auf 60 erwärmt, dann eine Lösung von 376 g Epibromhydrin in 500 ml Dimethylsulfoxyd bei Raumtemperatur zugetropft und 16 Stunden gerührt. Man giesst in Wasser, extrahiert mit Essigester und engt bis zur Kristallisation die Essigesterextrakte ein, Smp. 175 bis 177 .
Beispiel 2
2-Methyl-2-[2-hydroxy-3-(4-oxindolyloxy) - propyl-amino]propionsäureäthylester
Man verfährt wie in Beispiel 1 beschrieben, verwendet jedoch anstatt 3-Amino-3-methylbutin oc-Aminoisobuttersäure- äthylester. Die Titelverbindung kristallisiert aus Äther, Smp. 158 bis 160".
The invention relates to a process for the preparation of new oxindoles of the formula 1, in which R1 is hydrogen or a lower alkyl radical and R2 is an alkynyl radical whose triple bond is not in the x, 3-position to the nitrogen atom. to which the alkynyl radical is bonded or denotes a carbalkoxyalkyl radical and its acid addition salts to counter ', tattl.
If 9 stands for lower alkyl, this alkyl radical contains in particular 1 to 4, preferably 1 carbon atom.
If R2 represents an alkynyl group, this contains in particular 3 to 7 carbon atoms. A preferred group of this series is 1,1-dimethyl-2-propynyl.
If R .. represents a carbalkoxyalkyl group, its alkoxy radical contains in particular 1 to 4, preferably 1 or 2 carbon atoms and its alkyl radical contains in particular 1 to 6 carbon atoms.
Particularly preferred are compounds in which R1 is hydrogen and in which R2 is branched on the a-carbon atom.
According to the invention, the oxindoles of the formula I and their acid addition salts are obtained by reacting compounds of the formula II in which R has the above meaning with amines of the formula III in which R2 has the above meaning, and the compounds of the formula I thus obtained as wins free bases or as acid addition salts.
Acid addition salts can be prepared from the free bases in a known manner and vice versa.
The reaction of the compounds of the formula II with amines of the formula III can be carried out by known methods and is carried out, for example, in an organic solvent which is inert under the reaction conditions, e.g. in an aromatic hydrocarbon such as benzene, toluene, xylene, in a cyclic ether such as dioxane, tetrahydrofuran, in amyl alcohol.
The reaction temperature can be between 20 and 1500: in general, reflux is preferably used at the boiling point of the reaction mixture. The reaction time depends on the reaction temperature.
The compounds of the formula I prepared by the above process can be worked up and purified by known methods.
The connections detu pe, - FSîe IrIrSn e.g. by reacting the sodium salts of the corresponding 4-hydroxyoxindoles of the formula IV, in which R1 has the above meaning, with epibromohydrin in dimethyl sulfoxide as the solvent.
After the reaction has ended, it is poured into water and extracted with ethyl acetate. The ethyl acetate extracts are concentrated until the epoxypropoxyindole crystallizes.
Of the compounds of the formula IV, 4-hydroxyoxindole and 4-hydroxy-1 methyloxindole are known. The new compounds of formula IV, such as 4-hydroxy-1-methyloxindole, e.g. by cyclization of the corresponding N -alkyl-N-chloroacetyl.o-anisidines and dimethylation (ether cleavage) of the 1 -alkyl-4-methoxyoxindoles thus obtained,
If the preparation of the starting compounds is not described, these are known or can be prepared analogously to known methods.
The new compounds of the formula I and their pharmacologically acceptable acid addition salts have interesting pharmacodynamic properties with low toxicity and can therefore be used as medicaments,
The new substances show an inhibition of the positively inotropic adrenaline effect in the spontaneously beating isolated guinea pig atrium and lead to a strong inhibition of the tachycardia and blood pressure lowering caused by isoproterenol [1 (3, 4-dihydroxyphenyl) -2-isopropylaminoethanol in the anesthetized whole animal (cat, dog).
The compounds accordingly have a blocking effect on the 3 adrenergic receptors and can therefore i.a. for the prophylaxis and therapy of coronary diseases, in particular for the treatment of angina pectoris, for the treatment of hyperkinetic cardiac syndrome and the conditions resulting from muscular-hypertrophic, subvalvular aortic stenosis.
Because of their antiarrhythmic effects, the compounds are also suitable for the treatment of cardiac arrhythmias.
The doses to be used naturally vary depending on the type of substance used, the administration and the condition to be treated.
In the following examples, which illustrate the invention in more detail but are not intended to restrict its scope in any way, all temperatures are given in degrees Celsius and are uncorrected.
EMI1.1
Example I.
4- [2-hydroxy-3- (2-methyl-3-butyn-2-ylamino) propoxyl] oxindole
3 g of 4- (2,3-epoxypropoxy) oxindole, 9 g of 3-amino-3-methylbutyne and 40 ml of tetrahydrofuran are heated to the boil for 2 days with stirring. The hot solution is filtered and allowed to crystallize. The title compound melts from 172 to 174 ".
The 4- (2,3-epoxypropoxy) oxindole used as starting material was prepared as follows:
273 g of 4-hydroxyoxindole, 1300 ml of dimethyl sulfoxide and 55.8 g of 80% sodium hydride are heated to 60 for 1/2 hour, then a solution of 376 g of epibromohydrin in 500 ml of dimethyl sulfoxide is added dropwise at room temperature and stirred for 16 hours. It is poured into water, extracted with ethyl acetate and the ethyl acetate extracts are concentrated until crystallization, mp 175 to 177.
Example 2
Ethyl 2-methyl-2- [2-hydroxy-3- (4-oxindolyloxy) propyl-amino] propionate
The procedure described in Example 1 is followed, but instead of 3-amino-3-methylbutyne, oc-aminoisobutyric acid ethyl ester is used. The title compound crystallizes from ether, m.p. 158 to 160 ".
Claims (1)
Priority Applications (19)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE793073D BE793073A (en) | 1971-06-24 | Aminoalkoxyoxindole derivs - as beta-adren ergic blockers | |
| CH924871A CH547801A (en) | 1971-06-24 | 1971-06-24 | 4 and 7-Aminopropoyx-oxindole derivs - useful as anti-arrhythmics and beta-adrenergic blockers |
| SE7207867A SE379196B (en) | 1971-06-24 | 1972-06-15 | |
| US00263768A US3825558A (en) | 1971-06-24 | 1972-06-19 | Substituted aminopropoxy-2-indolinones |
| NL7208332A NL7208332A (en) | 1971-06-24 | 1972-06-19 | |
| HUSA002367 HU164321B (en) | 1971-06-24 | 1972-06-20 | |
| GB2874472A GB1391828A (en) | 1971-06-24 | 1972-06-20 | Oxindole derivatives |
| DD163906A DD99785A5 (en) | 1971-06-24 | 1972-06-22 | |
| BE785282A BE785282A (en) | 1971-06-24 | 1972-06-22 | NEW OXINDOLE DERIVATIVES, THEIR PREPARATION AND MEDICINAL PRODUCTS CONTAINING THESE DERIVATIVES |
| RO7483072A RO62636A (en) | 1971-06-24 | 1972-06-22 | PROCESS FOR THE PREPARATION OF OXINDOL DERIVATIVES |
| IL39742A IL39742A0 (en) | 1971-06-24 | 1972-06-22 | Substituted oxindoles,their preparation and pharmaceutical compositions containing them |
| PL15620572A PL83679B1 (en) | 1971-06-24 | 1972-06-22 | |
| DE2230426A DE2230426A1 (en) | 1971-06-24 | 1972-06-22 | PROCESS FOR PRODUCING NEW HETEROCYCLIC COMPOUNDS |
| RO7483172A RO62637A (en) | 1971-06-24 | 1972-06-22 | PROCESS FOR THE PREPARATION OF OXINDOL DERIVATIVES |
| JP47063153A JPS5820955B1 (en) | 1971-06-24 | 1972-06-23 | |
| ES404174A ES404174A1 (en) | 1971-06-24 | 1972-06-23 | PROCEDURE FOR OBTAINING SUBSTITUTE OXIDOLS. |
| AT541172A AT330169B (en) | 1971-06-24 | 1972-06-23 | Process for the preparation of new oxindoles and their salts |
| FR7222696A FR2143343B1 (en) | 1971-06-24 | 1972-06-23 | |
| AU43903/72A AU4390372A (en) | 1971-06-24 | 1972-06-26 | Organic compounds |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH924871A CH547801A (en) | 1971-06-24 | 1971-06-24 | 4 and 7-Aminopropoyx-oxindole derivs - useful as anti-arrhythmics and beta-adrenergic blockers |
| DE19722262285 DE2262285A1 (en) | 1972-12-20 | 1972-12-20 | Aminoalkoxyoxindole derivs - as beta-adren ergic blockers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH547801A true CH547801A (en) | 1974-04-11 |
Family
ID=25704508
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH924871A CH547801A (en) | 1971-06-24 | 1971-06-24 | 4 and 7-Aminopropoyx-oxindole derivs - useful as anti-arrhythmics and beta-adrenergic blockers |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH547801A (en) |
-
1971
- 1971-06-24 CH CH924871A patent/CH547801A/en not_active IP Right Cessation
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