US3825558A - Substituted aminopropoxy-2-indolinones - Google Patents

Substituted aminopropoxy-2-indolinones Download PDF

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Publication number
US3825558A
US3825558A US00263768A US26376872A US3825558A US 3825558 A US3825558 A US 3825558A US 00263768 A US00263768 A US 00263768A US 26376872 A US26376872 A US 26376872A US 3825558 A US3825558 A US 3825558A
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Prior art keywords
oxindole
carbon atoms
compound
methyl
hydroxy
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Expired - Lifetime
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US00263768A
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F Seemann
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Sandoz AG
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Sandoz AG
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Priority claimed from CH924771A external-priority patent/CH547800A/de
Priority claimed from CH924871A external-priority patent/CH547801A/de
Application filed by Sandoz AG filed Critical Sandoz AG
Priority claimed from DE19722262285 external-priority patent/DE2262285A1/de
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    • 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

Definitions

  • R is hydrogen or alkyl
  • R is a substituted or unsubstituted aromatic or aliphatic hydrocarbon and R is hydrogen or a carbonyl substituent and the side chain is in the 4 or 7 position of the oxindole nucleus.
  • the compounds possess pharmacological properties.
  • the present invention relates to heterocyclic compounds and more specifically to substituted oxindoles.
  • the present invention provides compounds of formula I,
  • R is alkyl of 1 to 6 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxyalkyl of 3 to 10 carbon atoms, the oxygen atom thereof being separated from the nitrogen atom by at least 2 carbon atoms; phenylalkyl of 8 to 12 carbon atoms; the phenyl being separated from the nitrogen atom by at least 2 carbon atoms; phenylalkyl of 8 to 12 carbon atoms, mono-substituted by alkyl of 1 to 5 carbon atoms or alkoxy of 1 to 5 carbon atoms, the phenyl being separated from the nitrogen atom by at least 2 carbon atoms; alkynyl of 2 to 7 carbon atoms; or carbalkoxyalkyl, the alkoxy substitnent thereof having 1 to 4 carbon atoms and the alkyl substituent thereof having 1 to 6 carbon atoms;
  • R is hydrogen, or COA, 6 wherein A is alkyl of 1 to 12 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms substituted by alkyl of 1 to 4 carbon atoms, or a 5- or 6-membered oxygen-containing heterocycle, and the aminopropoxy side chain is in the 4 or 7 position of the oxindole nucleus.
  • R is alkyl
  • representative examples are methyl, ethyl and n-propyl.
  • R is alkyl of more than 2 carbon atoms, this is preferably branched, especially on the a carbon atom. Typical examples are, isopropyl, sec.butyl, tert.butyl, 3- pentyl and tert.pentyl.
  • R is phenylalkyl
  • representative examples are 3- phenylpropyl, l,1dimethyl-3-phenylpropyl and l-methyl- 3-phenylpropyl.
  • phenyl is alkoxyor alkyl-substituted, particularly suitable substituents are methoxy as alkoxy substituent, as for example in 2-(4-methoxyphenyl)-1-methylethyl, and methyl as alkyl substituent.
  • R is cycloalkyl, this is preferably of 3 to 6 carbon atoms, e.g. cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • the triple bond is preferably situated in a position other than in an a-position to the nitrogen atom to which the alkynyl is bound.
  • a preferred group of this series is inter alia 1,1-dimethyl-2-propynyl.
  • R is carbalkoxyalkyl
  • alkoxy substituent are methoxy and ethoxy and the alkyl substituent is preferably branched in an a-position to the nitrogen atom to which it is bound.
  • a preferred example of carbalkoxyalkyl is l-methyl-l-(methoxycarbonyl)ethyl.
  • A is alkyl
  • this preferably contains 1 to 8 carbon atoms, particularly 1 to 4 carbon atoms.
  • alkyl substituted by alkyl When A is cycloalkyl substituted by alkyl, the preferred alkyl substituent is methyl.
  • Preferred alkylated cycloalkyl groups are those which are monoalkylated in the l-position. A typical example of this series is l-methylcyclohexyl.
  • A denotes a 5- or 6- membered, oxygen-containing heterocycle, this may, for example, be tetrahydropyranyl or furyl.
  • the present invention further provides a process for the production of a compound of formula I, comprising (a) reacting a compound of formula III,
  • R is as defined above, and the epoxypropoxy side chain is in the 4 or 7 position of the oxindole nucleus, with an amine of formula IV,
  • R R and A are as defined above, and the aminopropoxy side chain is in the 4 to 7 position of the oxindole nucleus, or
  • R is alkyl of 1 to -6 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxyalkyl of 3 to 10 carbon atoms, the oxygen atom thereof being separated from the nitrogen atom by at least 2 carbon atoms; phenylalkyl of 8 to 12 carbon atoms, the phenyl being separated from the nitrogen atom by at least 2 carbon atoms; phenylalkyl of 8 to 12 carbon atoms mono-substituted by alkyl of 1 to carbon atoms or alkoxy of 1 to 5 carbon atoms, the phenyl being separated from the nitrogen atom by at least 2.
  • the compounds of formula I may exist either in free base or acid addition salt forms.
  • Acid addition salt forms may be produced from free base forms in manner known per se and vice versa.
  • reaction of a compound of formula III with an amine of Formula IV may, for example, be effected in an inert organic solvent, e.g. an aromatic hydrocarbon such as benzene, toluene or xylene, a cyclic ether such as dioxane or tetrahydrofuran, or amyl alcohol.
  • an aromatic hydrocarbon such as benzene, toluene or xylene
  • a cyclic ether such as dioxane or tetrahydrofuran
  • amyl alcohol e.g. an aromatic hydrocarbon such as benzene, toluene or xylene
  • a cyclic ether such as dioxane or tetrahydrofuran
  • the reaction temperature may range between 20 and 150 C.; the reaction is preferably effected at the boiling temperature of the reaction mixture at reflux.
  • the reaction time is dependent on the reaction temperature.
  • Acylation of the resulting compound of formula Ia to obtain a compound of formula 1b is effected, for example, by adding an excess of an acid ACOOH, wherein A is as defined above, to a compound of formula Ia, and adding an excess of the corresponding anhydride to the resulting reaction mixture.
  • reaction may be effected in an inert organic solvent, e.g. hexametapol, a chlorinated aliphatic hydrocarbon such as chloroform, or a cyclic or open chain ether such as dioxane.
  • an inert organic solvent e.g. hexametapol, a chlorinated aliphatic hydrocarbon such as chloroform, or a cyclic or open chain ether such as dioxane.
  • the reaction temperature may range between room temperature and approximately 120 C.
  • the reaction time is dependent on the reaction temperature.
  • reaction mixture may be worked up, e.g. by pouring it on ice, making it alkaline with lye or ammonia and extracting with a watermiscible inert organic solvent, e.g. ethyl acetate, a cyclic or open chain ether such as diethyl ether, or a chlorinated aliphatic hydrocarbon such as methyl chloride.
  • a watermiscible inert organic solvent e.g. ethyl acetate, a cyclic or open chain ether such as diethyl ether, or a chlorinated aliphatic hydrocarbon such as methyl chloride.
  • danger of an N-acylation may thus be eliminated by the protonization of the amino group of the aminopropoxy side chain; however, protonization is not essential especially when R is bound to the nitrogen atom by a tertiary carbon atom.
  • the reaction is effected in the presence of e.g. hydrogen chloride, the compound of formula Ib crystallizes in hydrochloride form, and working up of the reaction mixture is not necessary.
  • Acylation may naturally likewise be effected with an acid halide. In this case the reaction is preferably effected at room temperature or at a slightly elevated temperature.
  • Debenzylation of a compound of formula V may, for example, be effected by hydrogenation in the presence of a catalyst, preferably a palladium catalyst in an inert organic solvent, e.g. ethyl acetate, or a cyclic or open chain ether such as diethyl ether, and is preferably effected at room temperature and normal pressure.
  • a catalyst preferably a palladium catalyst in an inert organic solvent, e.g. ethyl acetate, or a cyclic or open chain ether such as diethyl ether, and is preferably effected at room temperature and normal pressure.
  • the compounds of formula III may, for example, be obtained by reaction of a salt, e.g. sodium salt, of the corresponding 4-hydroxy or 7-hydroxy oxindole with an epihalohydrin, e.g. epibromhydrin, conveniently in dimethyl sulphoxide as solvent.
  • a salt e.g. sodium salt
  • an epihalohydrin e.g. epibromhydrin
  • working up may be effected by pouring the reaction mixture into water and extracting with ethyl acetate.
  • the ethyl acetate extracts may be concentrated until the epoxypropoxy-oxindole crystallizes.
  • R1 Va wherein R and R are as defined above, and the aminopropoxy side chain is in the 4 or 7 position of the oxindole nucleus, may be obtained in a manner analogous to the process for the production of compounds of formula Ia, by reaction of a compound of formula III with the corresponding benzylamine.
  • om-bnwm-fr-omQ 4 O l l wherein R R and A are as defined above, and the aminopropoxy side chain is in the 4- or 7-position of the oxindole nucleus, may be obtained by acylation of a compound of formula Va in analogous manner to that hereinbefore described for the production of compounds of formula Ib.
  • the dosage administered will, of course, vary depending upon the compound employed, mode of administration and treatment desired. However, in general, satisfactory results are obtained when administered at a daily dosage of between about 0.01 and mg./kg. animal body weight as a single dose. In the case of compounds of formula Ia, this dose may be administered as a divided dose two or three time daily or in retard form. In the case of compounds of formula Ib, this dose may, if necessary, be administered as a divided dose twice daily.
  • the total daily dosage for arenteral or oral administration is in the range of from about 1 to 500 mg., and unit dosage forms suitable for parenteral or oral administration comprise from about 0.3 to 500 mg.
  • a compound of formula Ia in the case of a compound of formula Ia, or from 0.2 to 500 mg. in the case of a compound of formula Ib, in the pharmaceutical composition incorporating a solid or liquid pharmaceutical carrier or diluent.
  • the preferred mode of administration is oral administration.
  • a suitable form of pharmaceutical composition for oral administration is a tablet.
  • Free base and acid addition salt forms of the compounds of formula I exhibit the same type of activity.
  • Examples of pharmaceutically acceptable acid addition salt forms are the hydrochloride, hydrogen oxalate and oxalate forms.
  • the preferred class of compounds are those wherein the aminopropoxy side chain is in the 4-position of the oxindole nucleus, particularly such compounds wherein R is hydrogen.
  • a further preferred subclass of such compounds are those wherein R is alkyl of more than 2 carbon atoms and is branched, particularly at the a-POSitiOIl with respect to the nitrogen atom to which R is bound. Examples of specific preferred compounds are:
  • EXAMPLE 1 4-(2-Hydroxy-3-isopropylaminopropoxy)oxindole (free base form) [process (a)] 25.5 g. of 4-(2,3-epoxypropoxy)oxindole are taken up in 30 cc. of isopropylamine and cc. of dioxane, and the mixture is allowed to stand at room temperature for 24 hours. The reaction mixture is evaporated to dryness at reduced pressure, the evaporation residue is subsequently partitioned between ethyl acetate and l N tartaric acid, and the tartaric acid extracts are made alkaline while cooling with ice.
  • the 4-(2,3-epoxypropoxy)oxindole, used as starting material, is produced as follows:
  • EXAMPLE 2 4-(3-tert.Butylamino-2-hydroxyprop0xy)oxindole (free base form) [process (a)] 2.0 g. of 4-(2,3-epoxypropoxy)oxindole, 6 cc. of tert.- butylamine and 50 cc. of dioxane are heated to the boil for 18 hours. The reaction solution is filtered whilst hot with the addition of some active charcoal and is then allowed to crystallize. The title compound has a M.P. of 197-198.
  • EXAMPLE 3 7-(2-Hydroxy-3-isopropylaminopropoxy)oxindole (free base form) [process (b)] The process is effected in a manner analogous to that described in Example 1, except that 7-hydroxy -oxindole is used in place of 4-hydroxy-oxindole, and benzyl isopropylamine is used in place of isopropylamine, and instead of etfecting the reaction at room temperature it is effected in an autoclave at 150 for 14 hours.
  • reaction solution is evaporated to dryness, and the residue is extracted between ethyl acetate and l N tartaric acid solution, the combined tartaric acid phases are made alkaline with 2 N caustic soda solution while cooling and are extracted with methylene chloride.
  • methylene chloride extracts over magnesium sulphate and concentrating by evaporation at reduced pressure
  • the oily crude product is chromatographed on silica gel with methylene chloride saturated with ammonia and the addition of to of methanol, and the so purified title compound is recrystallized from ethyl acetate.
  • M.P. 9698 M.P. 9698.
  • EXAMPLE 5' 4-[2-Hydroxy-3-(2-methyl-3-butyn-2-ylamino)propoxy] oxindole (free base form) [process (a)] 3 g. of 4-(2,3-epoxypropoxy)oxindole, 9 g. of 3-amino- 3-methyl butyne and cc. of tetrahydrofuran are heated to the boil while stirring for 2 days. The hot solution is filtered and is allowed to crystallize. The title compound has a M.P. of 172-174".
  • EXAMPLE 7 4-[2-Hydroxy-3-(2-rnethyl-3-butyn-2-ylamino)propoxy] oxindole (free base form) [process (a)] The process is effected as described in Example 5, except that pure 4-(2,3-epoxypropoxy)oxindole is reacted with 3-amino-3-methyl butyne, whereby the title compound, having a M.P. of 172174, is obtained.
  • EXAMPLE 8 4- (3-tert.Butylamino-Z-hydroxypropoxy oxindole (free base form) [process (b)] 4.1 g. of 4-(2,3-epoxypropoxy)oxindole are reacted with 8.15 g. of benzyl tert.butylamine in cc. of dioxane in an autoclave at 150. The resulting 4-[3-(benzyl tert. butylamino) 2 hydroxypropoxy]oxindole (M.P. 141-143", from ethyl acetate) is debenzylated with hydrogen in 150 cc. of methanol and in the presence of 2.5 g. of a palladium catalyst (10% of palladium on charcoal) to obtain the title compound. M.P. 197198.
  • EXAMPLE 9 4-(3-Cyclopentylamino-Z-hydroxypropoxy)oxindole (free base form) [process (b)] 5 g. of 4-(2,3-epoxypropoxy) oxindole are taken up in 150 cc. of dioxane, and heating is effected with 6.4 g. of benzyl cyclopentylamine in an autoclave to 130 for 18 hours. The reaction solution is evaporated to dryness at reduced pressure, the residue is partitioned between ethyl acetate and 1 N tartaric acid solution, the tartaric acid phases are then made alkaline with 2 N caustic soda solution while cooling and are extracted with methylene chlo- 8 ride.
  • EXAMPLE 10 4- ⁇ 2-Hydroxy-3- [2- (4-methoxyphenyl ethylamino]propoxy ⁇ oxindole (free base form) [process (b)] The process is effected as described in Example 9, and the title compound, having a M.P. of 151153, from ethyl acetate, is obtained by debenzylation of 4- ⁇ N-benzyl- 2 hydroxy 3 [2 (4-methoxyphenyl)ethylamino]propoxy ⁇ oxindole (M.P.
  • reaction mixture is poured on ice and is made alkaline with 10% aqueous ammonia solution, extraction is effected with ether, the extracts are dried over magnesium sulphate, and the solvent is evaporated at reduced pressure.
  • the resulting compound is converted into its hydrogen oxalate and is recrystallized from methanol. M.P. 182-185.
  • EXAMPLE 12 4-[3-Cyclopentylamino 2-(4-tetrahydropyranylcarbonyloxy)propoxy] oxindole (hydrogen oxalate form] [process (b)] A solution of 1.4 g. of 4-tetrahydropyrancarboxylic acid chloride in 20 cc. of dioxane is added dropwise while stirring to a solution of 1.2 g. of 4-(3-benzylcyclopentylamino-2-hydroxypr0poxy)oxindole and 0.42 g. of pyridine in 15 cc. of dioxane, and the reaction solution is subsequently heated to the boil for 4 /2 hours.
  • reaction solution is evaporated to dryness at reduced pressure, ice is added, and the solution is made alkaline with 10% aqueous ammonia solution, extraction is effected with ether, the extracts are dried over magnesium sulphate, and the solvent is evaporated at reduced pressure.
  • the 4-[3-benzylcyclopentylamino 2 (4-tetrahydropyranylcarbonyloxy)propoxy] oxindole obtained as an oil is debenzylated with hydrogen in the presence of 1 g. of a palladium catalyst (10% of palladium on charcoal) in 25 cc. of tetrahydrofuran.
  • the resulting compound is converted into its hydrogen oxalate and crystallized from ethanol in druses. M.P. 168-171".
  • EXAMPLE 14 4-(3-tert.Butylamino-Z-pivaloyloxypropoxy)oxindole (oxalate form) [process (a)] 2.3 g. of 4-(3-tert.butylamino-2-hydroxypropoxy)oxindole are stirred at room temperature over night with 15 g. of pivalic acid and 1.7 g. of pivalic acid anhydride. The reaction solution is poured on ice and is made alkaline with aqueous ammonia solution, extraction is effected with ether, the extracts are dried over magnesium sulphate, and the solvent is evaporated at reduced pressure. The resulting compound is converted into its oxalate and is crystallized from ethanol/ethyl acetate. M.P. 230-232.
  • R is alkyl of 1 to 6 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; alkoxyalkyl of 3 to 10 carbon atoms, the oxygen atom thereof being separated from the nitrogen atom by at least 2 carbon atoms; phen ylalkyl of 8 to 12 carbon atoms, the phenyl being separated from the nitrogen atom by at least 2 carbon atoms; phenylalkyl of 8 to 12 carbon atoms mono-substituted by alkyl of 1 to 5 carbon atoms or alkoxy of 1 to 5 carbon atoms, the phenyl being separated from the nitrogen atom by at least 2 carbon atoms; alkynyl of 2 to 7 carbon atoms; or carbalkoxyalkyl, the alkoxy substituent thereof having 1 to 4 carbon atoms and the alkyl substituent thereof having 1 to 6 carbon atoms;
  • R is hydrogen; or -COA, wherein A is alkyl of l to 12 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms substituted by alkyl of 1 to 4 carbon atoms, or a 5- or 6-membered oxygen heterocycle having one oxygen atom; and the aminopropoxy side chain is in the 4 or 7 position of the oxindole nucleus,
  • the compound of Claim 1 which is 4-(3-cyclopentylamino-2-hydroxypropoxy oxindole 14.
  • the compound of Claim 1 which is 4-(3-cyclopentylamino-2-heptanoyloxypropoxy oxindole 16.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US00263768A 1971-06-24 1972-06-19 Substituted aminopropoxy-2-indolinones Expired - Lifetime US3825558A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH925171 1971-06-24
CH924771A CH547800A (de) 1971-06-24 1971-06-24 Verfahren zur herstellung neuer oxindole.
CH924871A CH547801A (de) 1971-06-24 1971-06-24 Verfahren zur herstellung neuer oxindole.
DE19722262285 DE2262285A1 (de) 1972-12-20 1972-12-20 Verfahren zur herstellung neuer heterocyclischer verbindungen

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US (1) US3825558A (enrdf_load_stackoverflow)
AU (1) AU4390372A (enrdf_load_stackoverflow)
BE (1) BE785282A (enrdf_load_stackoverflow)
DD (1) DD99785A5 (enrdf_load_stackoverflow)
DE (1) DE2230426A1 (enrdf_load_stackoverflow)
FR (1) FR2143343B1 (enrdf_load_stackoverflow)
GB (1) GB1391828A (enrdf_load_stackoverflow)
NL (1) NL7208332A (enrdf_load_stackoverflow)
SE (1) SE379196B (enrdf_load_stackoverflow)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3965095A (en) * 1972-06-23 1976-06-22 Sandoz Ltd. Oxindole derivatives
US4137331A (en) * 1974-06-19 1979-01-30 Sandoz Ltd. 3-Piperidino-2-hydroxypropoxy substituted-2-indolinones
US4395559A (en) * 1979-12-07 1983-07-26 Hoffmann-La Roche Inc. 2,3-Indoledione derivatives
US4642309A (en) * 1983-03-23 1987-02-10 Boehringer Mannheim Gmbh Indolin-2-one derivatives preparation thereof and intermediates for the preparation thereof
US4826847A (en) * 1984-07-18 1989-05-02 Boehringer Mannheim Gmbh Beta-blocking oxindole derivatives
US4868306A (en) * 1983-10-25 1989-09-19 Fisons Plc Compounds
US4994474A (en) * 1986-02-14 1991-02-19 Sanofi Alkyl- or aryl-aminoalkoxy-benzene-sulfonyl indoles

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2905877A1 (de) 1979-02-16 1980-08-28 Boehringer Mannheim Gmbh Neue aminopropanolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE3512627A1 (de) * 1985-04-06 1986-10-09 Boehringer Mannheim Gmbh, 6800 Mannheim Amino-propanol-derivate, verfahren zu deren herstellung, verwendung derselben und diese enthaltende arzneimittel
US6075040A (en) * 1996-09-05 2000-06-13 Eli Lilly And Company Selective β3 adrenergic agonists
ZA967892B (en) * 1995-09-21 1998-03-18 Lilly Co Eli Selective β3 adrenergic agonists.
ES2171839T3 (es) * 1996-09-05 2002-09-16 Lilly Co Eli Analogos de carbazol como agonistas adrenergicos selectivos de beta3.
CO5011072A1 (es) * 1997-12-05 2001-02-28 Lilly Co Eli Etanolaminas pirazinil substituidas como agfonistas de los receptores

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3965095A (en) * 1972-06-23 1976-06-22 Sandoz Ltd. Oxindole derivatives
US4137331A (en) * 1974-06-19 1979-01-30 Sandoz Ltd. 3-Piperidino-2-hydroxypropoxy substituted-2-indolinones
US4395559A (en) * 1979-12-07 1983-07-26 Hoffmann-La Roche Inc. 2,3-Indoledione derivatives
US4642309A (en) * 1983-03-23 1987-02-10 Boehringer Mannheim Gmbh Indolin-2-one derivatives preparation thereof and intermediates for the preparation thereof
US4868306A (en) * 1983-10-25 1989-09-19 Fisons Plc Compounds
US4826847A (en) * 1984-07-18 1989-05-02 Boehringer Mannheim Gmbh Beta-blocking oxindole derivatives
US4994474A (en) * 1986-02-14 1991-02-19 Sanofi Alkyl- or aryl-aminoalkoxy-benzene-sulfonyl indoles

Also Published As

Publication number Publication date
BE785282A (fr) 1972-12-22
FR2143343A1 (enrdf_load_stackoverflow) 1973-02-02
GB1391828A (en) 1975-04-23
SE379196B (enrdf_load_stackoverflow) 1975-09-29
NL7208332A (enrdf_load_stackoverflow) 1972-12-28
FR2143343B1 (enrdf_load_stackoverflow) 1976-03-05
DD99785A5 (enrdf_load_stackoverflow) 1973-08-20
DE2230426A1 (de) 1973-01-11
AU4390372A (en) 1974-01-03

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