US3821387A - The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles - Google Patents

The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles Download PDF

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Publication number
US3821387A
US3821387A US00504087A US50408765A US3821387A US 3821387 A US3821387 A US 3821387A US 00504087 A US00504087 A US 00504087A US 50408765 A US50408765 A US 50408765A US 3821387 A US3821387 A US 3821387A
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parkinsonism
indole
ethyl
substituted
indoles
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US00504087A
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English (en)
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W Welstead
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AH Robins Co Inc
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AH Robins Co Inc
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Priority to US00504087A priority Critical patent/US3821387A/en
Priority to US556879A priority patent/US3642803A/en
Priority to GB25960/69A priority patent/GB1167563A/en
Priority to GB44649/66A priority patent/GB1167562A/en
Priority to BR18366866A priority patent/BR6683668D0/pt
Priority to SE14453/66A priority patent/SE312556B/xx
Priority to FR1602626D priority patent/FR1602626A/fr
Priority to AT993066A priority patent/AT269870B/de
Priority to DE19661620224 priority patent/DE1620224A1/de
Priority to NL6615028A priority patent/NL6615028A/xx
Priority to CH1537666A priority patent/CH505824A/de
Priority to FR92054A priority patent/FR6253M/fr
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Publication of US3821387A publication Critical patent/US3821387A/en
Priority to US05/586,699 priority patent/USRE28973E/en
Assigned to A.H. ROBINS COMPANY, INCORPORATED, A DE CORP. reassignment A.H. ROBINS COMPANY, INCORPORATED, A DE CORP. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). 12-14-89 DELAWARE Assignors: A.H. ROBINS COMPANY, INCORPORATED, A CORP. OF VA (INTO)
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients

Definitions

  • the present invention relates to certain heterocyclic organic compounds which may be referred to as 3- (omega-substituted alkyl) indoles, acid addition and quaternary ammonium salts thereof, therapeutic compositions containing the same as active ingredients, and methods of making and administering them.
  • novel compounds of the present invention have utility as physiologically active agents and are particularly effective in diminishing the tremors and muscular rigidity of Parkinsonism.
  • the compounds are also useful as tranquilizers.
  • Prior art literature contains examples of 3-(omega substituted alkyl) indoles. Those which have been examined in animal bodies have shown limited therapeutic value and are not disclosed to have anti'Parkinson activity. More recently a series of l-,2-, and 3-[2-(4- substituted piperazinyl)ethyl]indoles has been the subject of US. Pat. No. 3,188,313 with the disclosure of their therapeutic application as CNS depressants. However, these are likewise not disclosed to have anti- Parkinsonism acitivity.
  • Medicaments that have been used to ameliorate the symptoms of Parkinsonism have been derived from the belladonna group of alkaloids, particularly atropine and scopolamine; in addition synthetic medicinals such as Pa'rsidol (TM), Artane (TM), Kemadrin (TM) and Disipal (TM) among others and certain antihistamine compounds have been used with varying degrees of success. Although all of the aforementioned drugs have been of therapeutic value in treating the tremors and muscular rigidity of Parkinsonism, prior to this invention no single preparation has been found to be universally tolerated.
  • An additional object is the provision of compounds useful as anti-Parkinson agents and which produce minimal side effects.
  • a further ob ject is to provide a method of using said drugs in the treatment of living animal and especially mammalian bodies.
  • a still further object is to provide pharmaceutical compositions which embody the said agents.
  • a still further object is to provide a method for preparing said novel 3-(omega substituted alkyl) indoles. Additional objects will be apparent to one skilled in the art and still further objects will become apparent hereinafter.
  • novel compounds of the present invention can be represented by the following formula:
  • R is selected from the group consisting of hydrogen. lower-alkyl, lower-alkanoyl, aroyl, monocarbocyclic aryl, phenyl-lower-alkyl and cycloalkyl;
  • R is selected from the group consisting of hydrogen, lower-alkyl and monocarbocyclic aryl;
  • R" is selected from the group consisting of halogen having an atomic weight less than 80, trifluoromethyl, hydroxyl, lower-alkyl, loweralkoxy and aralkoxy;
  • R' is selected from the group consisting of monocarbocyclic aryl and hydrogen;
  • A is selected from the group consisting of hydrogen, loweralkyl, lower-alkynyl, lower alkanoyl, monocarbocyclic aryl, monocarbocyclic aroyl and monocarbocyclic aryl carbamoyl;
  • n is an integer from 0-3 inclusive and m is either zero or one.
  • lower-alkyl as used herein includes straight and branched chain radicals of up to five carbon atoms inclusive and is exemplified by such groups as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, amyl and the like.
  • Lower-alkoxy has the formula --o--lower-alkyl.
  • cycloalkyl as used herein includes primarily cyclic alkyl radicals containing three up to nine carbon atoms inclusive and encompasses such groups as cyclopropyl, cyclobutyl, cyclopentyl, methylcyclohexyl, ethylcyclopentyl and propylcyclohexyl. Included in the term phenyllower alkyl" are groups such as benzyl, phenethyl, methylbenzyl, phenpropyl and the like. Lower-allkanoyl has the formula Ill lower-alkyl. Aroyl has the formula monocarbocyclic aryl, and aralkoxyl has the formula: o-lower-alkyl-monocarbocyclic aryl.
  • monocarbocyclic aryl is meant a phenyl radical or a phenyl radical substituted by one or more substitutents selected from the group consisting of halogen having an atomic weight less than 80, lower-alkyl, hydroxy, carboxy, lower-alkoxy and trifluoromethyl.
  • the lower-alkyl and lower-alkoxy radicals can contain up to about three carbon atoms and each monocarbocyclic aryl radical, together with said substituents, can contain from six to about nine carbon atoms.
  • the monocarbocyclic aryl radical is substituted by more than one of the above substituents, the substituent can be the same or different and can occupyany of the available positions on the phenyl ring.
  • R represents a monocarbocyclic aryl radical it can represent an organic radical such as phenyl or a phenyl radical substituted by one or more substituentssuch as fluoro, chloro, bromo,
  • This invention also includes acid addition salts of the above defined bases formed with nontoxic organic and inorganic acids.
  • Such salts are easily prepared by methods known in the art.
  • the toxicity or nontoxicity of the salt is immaterial when the compounds are to be used as pharmaceuticals, they are most conveniently used in the form of nontoxic acidaddition or quaternary ammonium salts. Both toxic and nontoxic salts are therefore within the purview of the invention.
  • the acids which can be used to prepare the preferred nontoxic acid-addition salts are those which produce, when combined with the free bases, salts whose anions are relatively innocuous to the animal organism in therapeutic doses of the salts, so that beneficial physiological properties inherent in the free bases are not vitiated by side-effects ascribable to the anions.
  • the base is reacted with the calculated amount of organic or inorganic acid in aqueous miscible solvent, such as ethanol or isopropanol, with isolation of the salt by concentration and cooling, or the base is reacted with an excess of the acid in aqueous immiscible solvent, such as ethyl ether or isopropyl ether, with the desired salt separating directly.
  • aqueous miscible solvent such as ethanol or isopropanol
  • organic salts are those with maleic, fumaric, benzoic, ascorbic, pamoic, succinic, methanesulfonic, acetic, propionic, tartaric, citric, lactic, malic, citraconic, itaconic, hexamic, p-aminobenzoic, glutamic, stearic and the like.
  • inorganic salts are those with hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric and nitric acids.
  • this invention includes pharmaceutically acceptable, nontoxic quaternary ammonium salts of the above defined bases.
  • the quaternary ammonium salts are readily formed by treatment of the corresponding free base with the appropriate salt-forming substance, including, for example, methyl chloride, methyl bromide, methyl iodide, methyl sulfate, ethyl chloride, ethyl bromide, ethyl iodide, n-propyl chloride, n-propyl bromide, n-propyl iodide, isobutyl iodide, sec-butyl bromide, n-amyl chloride, n-amyl bromide, n-amyl iodide, isoamyl chloride, n-hexyl chloride, nhexyl bromide, n-hexyl iodide or similar quaternary salt-forming substances, according to general procedures which are
  • novel compounds of this invention are prepared starting from readily available selected indoles or from indoles prepared by the Fischer indole synthesis.
  • the indoles are reacted with oxalyl chloride at to 25C. according to the procedure of Speet'er and Anthony, J. Am. Chem. Soc. 76,6208-l0( 1954) in an organic solvent inert under the conditions of the reaction, such as ether, dioxane, and the like to give indole-3-glyoxyloyl chloride.
  • the preferred solvent is ether.
  • the indole-3-glyoxyloyl chloride is then reacted with an appropriate 4-substituted piperidine or 3-substituted pyrrolidine in a suitable solvent such as benzene, chloroform, dioxane, toluene, acetonitrile and the like, which will not enter into the reaction but which will provide a rection medium.
  • a suitable solvent such as benzene, chloroform, dioxane, toluene, acetonitrile and the like, which will not enter into the reaction but which will provide a rection medium.
  • An acid acceptor which may be an excess amount of the reacting pyrrolidine compound, a tertiary amine or an alkali metal salt of a weak acid may be used, the alkali metal salt of a weak acid, e.g., sodium carbonate, sodium bicarbonate, potassium carbonate, and the like being the preferred acid acceptor.
  • indole-3-glyoxyloyl chloride is not readily hydrolyzed by water at or about room temperature and in an alternative procedure the reaction between an indole-3-glyoxyloyl chloride and the selected substituted piperidine or pyrrolidine can be conveniently carried out in a chloroform-water mixture.
  • the alternate method is particularly convenient when the acid acceptor employed is an alkali metal salt of a weak acid.
  • The-purpose of the acid acceptor is to take up the hydrogen halide which is split out during the course of the reaction.
  • the reaction is conveniently carried out at or about room temperature for a period of about 3 to 5 hours.
  • Isolation of the product a l- (indol-3-ylglyoxyloyl)-3-substituted pyrrolidine or 4- substituted piperidine, is achieved by dilution of the reaction mixture with water, separation of the organic and aqueous layers, and drying and concentration of the organic layer.
  • the crude products are best purified by crystallization from a suitable solvent, chromatography or formation of a readily crystallizable organic or inorganic salt.
  • the preparation of the novel compounds of the present invention is not limited by the preceding described method and they can be prepared by alternative procedures.
  • appropriately substituted indole-3-acetic acids are prepared from appropriately substituted hydrazones by the Fischer indole synthesis.
  • the substituted indole-3-acetic acids thus prepared are reduced by metal hydrides to the corresponding substituted 3-(2-hydroxyethyl) indoles.
  • Reaction of the latter with a thionyl halide furnishes a substituted 3-(2-haloethyl) indole, the gaseous by-products sulfur dioxide and hydrogen halide being removed from the reaction system by application of a slight vacuum or by sweeping the by-product gases out of the reaction system by the use of an inert gas as, for example, nitrogen.
  • Preparation 3 b 3-Pyrrolidinol (0.95 g.; 0.01 mole) was added to a stirred mixture of 2.9 g. (0.01 mole) of 5,6? di'methoxy-ind0le-3-glyoxyloyl chloride, 4.0 g. of so dium carbonate and ml. of benzene. After stirring overnight at room temperature, 50 ml. of water was added. The mixture was stirred 30 minutes, filtered and the cake washed with water and then with benzene. The dried material weighed 1.45 g. (45 percent) and melted at 222 to 225.
  • trimethoxybenzoyloxy)-pyrrolidine trimethoxy-benzoyloxy)-pyrrolidine 1-[(2-Phenylindol-3-yl)glyoxyloyll]-3- ethoxypyrrolidine 1-[(5-Hydroxyindol-3-yl)glyoxylo yl]-3-(4- methoxyphenyl-carbamoyloxy)-pyrrolidine 1-(1ndol-3-y1glyoxyloyl)-3-(2-propynyloxy)- pyrrolidine 1-[(5,7-Dichloroindol-3-yl)glyoxyloyl]-3-(omethoxyphenoxy)-pyrrolidine 1-[( l -Ethylindol-3-yl)glyoxy1oyl]-3- hydroxypyrrolidine l-[(2,7-Dimethyl-4-chloroindol-3-yl)glyoxyloyl]
  • Example 1 3-[2-( 3-Hydroxypyrrolidinyl)ethyl]indole
  • a suspension of 11 g. (0.043- mole) of 1-(indol-3- ylglyoxyloyl)-3-pyrrolidinol in 50 ml. of tetrahydrofuran was added dropwise, under nitrogen, to a stirred suspension of 9.8 g. (0.026 mole) of lithium aluminum hydride in 100 ml. of tetrahydrofuran.
  • the mixture was refluxed for 2 hours, cooled, and treated with enough water to destroy the excess lithium aluminum hydride.
  • the resulting aluminum hydroxide was filtered off and washed thoroughly with tetrahydrofuran. The filtrate was evaporated on a rotating evaporator to an oil which solidified on standing. Crystallization from acetonitrile gave a melting point of 144-146; yield, 7.7 g. (78 percent).
  • Example 2 2-Methyl-3- ⁇ 2-[ 3-( 3 ,4,S-trimethoxybenzoyloxy )pyrrolidinyl- ]ethyl ⁇ indole
  • the mixture was stirred under anhydrous conditions for 24 hours, then treated with 25ml. of water and stirred an additional hour.
  • the chloroform layer was separated, dried over magnesium sulfate and evaporated on a rotating evaporator to a viscous oil.
  • Example 3 with tetrahydrofuran. Evaporation of the combined filtrates gave an oil which would not crystallize. The oil was dissolved in acetone and treated with dry HCl gas. On cooling 18.5 g. of impure product precipitated. Recrystallization from isopropanol-acetonitrile (90:10)
  • Example 4 ⁇ 2-[3-(3,4,S-Trimethoxybenzoyloxy)pyrrolidinyl ]ethyl ⁇ indole Y
  • 3 g. (0.013 mole) of 3-[2-(3- hydroxypyrrolidinyl)ethyl]indole, 3 g. (0.013 mole) of 3,4,5-trimethoxybenzoyl chloride and 5 g. (0.05 mole) of sodium carbonate in 40 ml. of chloroform was.
  • the product was chromatographed on a Florisil column (60-100 mesh) and eluted with benzene, then benzene with increasing amounts of acetone. At 10 percent acetone-benzene pure product began to elute from the column (TLC shows single spot); yield 4.3 g. (78 percent).
  • the glassy solid could be crystallized from benzene orbenzene-ligroin giving a solid which melted between 79 and 86 with gas evolution. Analysis as well as the infrared spectrum indicated thatthe solid was a benzene solvate.
  • Example 7 6-Dimethoxy-3-[2-( 3-hydroxypyrrolidinyl )ethyl]indole hydrochloride monohydrate
  • a mixture of 5.5 g. (0.017 mole of l-[(5,6- dimethoxy-indol-3-yl)glyoxyloyll-3-pyrrolidinol in 50 ml. of dry tetrahydrofuran was added dropwise to a stirred suspension of 2.85 g. (0.075 mole) of lithium aluminum hydride in 100 ml. of tetrahydrofuran under nitrogen. After addition the mixture was refluxed for 4 hours, cooled in ice and treated with a saturated sodium sulfate solution.
  • compositions comprising, as active ingredient, at least one of the compounds according to the invention in association with a pharmaceutical carrier or excipient.
  • the compounds may be presented in a form suitable for oral or parenteral administration.
  • compositions for oral administration can be solid or liquid and can take the form of capsules, tablets, coated tablets, suspensions, etc., such compositions comprising carriers or excipients conveniently used in the pharmaceutical art.
  • suitable tableting excipients inelude lactose, potato and maize starches, talc, gelatin, and stearic and 'silicic acids, magnesium stearate, and polyvinyl pyrrolidone.
  • the carrier or excipient may be -a sterile, parenterally acceptable liquid, e.g., water or a parenterally acceptable oil, e.g., araehis oil, contained in ampoules.
  • compositions may be formulated as dosage units, each unit being adapted to supply a fixed dose of active ingredient.
  • Tablets, coated tablets, capsules, and ampoules are examples of preferred dosage unit forms according to the invention.
  • Each dosage unit adapted for oral administration can conve-' niently contain 25 to 500 mg., and preferably 100 to 250 mg. of the active ingredient; whereas each dosage unit adapted for intramuscular administration can conveniently contain to 150 mg, and preferably 50 to 150 mg. of the active ingredient.
  • compositions within the preferred ranges given are as follows:
  • Tablets Ingredients MgJTab.
  • step No. l Add sufficient water portionwise 'to the blend from step No. l with careful stirring after each addition. Such additions of water and stirring continue until the mass is of a consistency to permit its conversion to wet granules.
  • the wet mass is converted to granules by passing it through the oscillating granulator, using 8-mesh screen.
  • the wet granules are then dried in an oven at 5.
  • the dried granules are then passed through an oscillating granulator, using a IO-mesh screen.
  • the lubricated granules are compressed on a suitable tablet press.
  • Intramuscular Injection Ingredients Per ml.
  • Active Ingredient 50.0 mg.
  • Isotonic Buffer Solution 4.0 q.s. to 2.0 ml.
  • Procedure I Dissolve the active ingredient in the buffer solution.
  • the ampoules are sealed under aseptic conditions.
  • a therapeutic composition for anti-Parkinsonism comprising (1) an effective amount of at least about I wherein:
  • R is selected from the group consisting of hydrogen
  • lower-alkyl lower-alkanoyl, benzoyl, phenyl, phenyllower-alkyl and cycloalkyl having three to nine carbon atoms; 7 i
  • R is selected from the group consisting of hydrogen
  • A is selected from the group consisting of hydrogen, lower-alkyl, lower-alkynyl, lower-alkanoyl, phenyl, benzoyl and N-phenyl carbamoyl;
  • n is zero or one and n is zero to three inclusive
  • a method of alleviating symptoms of Parkinsonism which comprises administering to a living animal body afflicted therewith an effective amount of a compound of claim 2.
  • a method of alleviating symptoms of Parkinsonism which comprises administering to a living animal body 7.
  • a method of alleviating symptoms of Parkinsonism which comprises administering to a living animal body afflicted therewith an effective amount of 3-[2-(4- h ydroxy-4-phenylpiperidinyl )ethyl lzindole.

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  • Chemical & Material Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Plural Heterocyclic Compounds (AREA)
US00504087A 1965-10-23 1965-10-23 The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles Expired - Lifetime US3821387A (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
US00504087A US3821387A (en) 1965-10-23 1965-10-23 The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles
US556879A US3642803A (en) 1965-10-23 1966-06-13 3-(omega-substituted alkyl)-indoles
GB25960/69A GB1167563A (en) 1965-10-23 1966-10-06 Novel 3-(2-Substituted Ethyl) Indoles and Processes for Their Manufacture
GB44649/66A GB1167562A (en) 1965-10-23 1966-10-06 Novel 3-(2-Substituted Ethyl)Indoles and Processes for Their Manufacture
BR18366866A BR6683668D0 (pt) 1965-10-23 1966-10-14 3-alcoil (omega substituido)-indois
SE14453/66A SE312556B (forum.php) 1965-10-23 1966-10-21
FR1602626D FR1602626A (forum.php) 1965-10-23 1966-10-22
AT993066A AT269870B (de) 1965-10-23 1966-10-24 Verfahren zur Herstellung neuer Indolderivate und ihrer Salze
DE19661620224 DE1620224A1 (de) 1965-10-23 1966-10-24 Verfahren zur Herstellung von Indolverbindungen
NL6615028A NL6615028A (forum.php) 1965-10-23 1966-10-24
CH1537666A CH505824A (de) 1965-10-23 1966-10-24 Verfahren zur Herstellung von in 3-Stellung substituierten Indolen
FR92054A FR6253M (forum.php) 1965-10-23 1967-01-20
US05/586,699 USRE28973E (en) 1965-10-23 1975-06-13 3-(Omega-substituted alkyl)-indoles

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US00504087A US3821387A (en) 1965-10-23 1965-10-23 The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles
US55687966A 1966-06-13 1966-06-13

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US05/586,699 Continuation-In-Part USRE28973E (en) 1965-10-23 1975-06-13 3-(Omega-substituted alkyl)-indoles

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US00504087A Expired - Lifetime US3821387A (en) 1965-10-23 1965-10-23 The treatment of parkinsonism with 3-(omega-substituted alkyl)-indoles
US556879A Expired - Lifetime US3642803A (en) 1965-10-23 1966-06-13 3-(omega-substituted alkyl)-indoles

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CH (1) CH505824A (forum.php)
DE (1) DE1620224A1 (forum.php)
FR (2) FR1602626A (forum.php)
GB (2) GB1167562A (forum.php)
NL (1) NL6615028A (forum.php)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0046179A1 (en) * 1980-07-07 1982-02-24 Hoechst-Roussel Pharmaceuticals Incorporated 3-(3-(4-(4-Fluorobenzoyl)piperidyl)propyl)-2-methyl indole and pharmaceutical composition containing it
US20160052924A1 (en) * 2013-03-27 2016-02-25 Bristol-Myers Squibb Company 2-keto amide derivatives as hiv attachment inhibitors

Families Citing this family (20)

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Publication number Priority date Publication date Assignee Title
US3912746A (en) * 1970-08-28 1975-10-14 American Cyanamid Co Substituted nitrogen containing heteroethyleneindoles
US4160862A (en) * 1972-06-12 1979-07-10 Sterling Drug Inc. 1-Acyl-3-(amino-lower-alkyl)indoles
US4031221A (en) * 1974-06-17 1977-06-21 American Hoechst Corporation Method of treating pain and hypertension
US4242347A (en) * 1979-06-18 1980-12-30 Ciba-Geigy Corporation Hypotensive indolylalkylpiperidyl guanidines and isoureas
US4861880A (en) * 1982-09-20 1989-08-29 Pfizer Inc. 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents
US4879391A (en) * 1982-09-20 1989-11-07 Pfizer Inc. 1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents
US4977178A (en) * 1982-09-20 1990-12-11 Pfizer Inc. Method of treating anxiety and depression with 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents
DE3308668A1 (de) * 1983-03-11 1984-09-13 Merck Patent Gmbh, 6100 Darmstadt Indolderivate
DE3430284A1 (de) * 1984-08-17 1986-02-27 Troponwerke GmbH & Co KG, 5000 Köln Neue tryptamin-derivate, ein verfahren zu ihrer herstellung und ihre verwendung
EP0187619A3 (de) * 1985-01-03 1987-08-26 Ciba-Geigy Ag 1,3-disubstituierte Tetrahydropyridine
EP0187122A3 (de) * 1985-01-03 1987-12-16 Ciba-Geigy Ag 1,3,4-Trisubstituierte Azacycloalkane bzw. Azacycloalkene
DE3835291A1 (de) * 1988-04-19 1989-11-02 Bayer Ag 1,3-disubstituierte pyrrolidine
US5274097A (en) * 1988-04-19 1993-12-28 Bayer Aktiengesellschaft 1,3-disubstituted pyrrolidines
SE9603283D0 (sv) * 1996-09-10 1996-09-10 Astra Ab New compounds
TW472045B (en) * 1996-09-25 2002-01-11 Astra Ab Protein kinase C inhibitor compounds, method for their preparation, pharmaceutical composition thereof and intermediate used for their preparation
AR017200A1 (es) 1997-12-23 2001-08-22 Astrazeneca Ab Compuestos inhibidores de la proteina cinasa c, sales farmaceuticamente aceptables de los mismos, formulaciones farmaceuitcas que los comprenden, usode las mismas y proceso para la sintesis de dichos compuestos
SE9800835D0 (sv) 1998-03-13 1998-03-13 Astra Ab New Compounds
KR100448748B1 (ko) * 1998-04-28 2004-09-18 엘비온 아게 하이드록시인돌, 이를 함유하는 약제 및 이의 제조방법
US6492406B1 (en) 1999-05-21 2002-12-10 Astrazeneca Ab Pharmaceutically active compounds
US6346625B1 (en) 1999-06-23 2002-02-12 Astrazeneca Ab Protein kinase inhibitors

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0046179A1 (en) * 1980-07-07 1982-02-24 Hoechst-Roussel Pharmaceuticals Incorporated 3-(3-(4-(4-Fluorobenzoyl)piperidyl)propyl)-2-methyl indole and pharmaceutical composition containing it
US20160052924A1 (en) * 2013-03-27 2016-02-25 Bristol-Myers Squibb Company 2-keto amide derivatives as hiv attachment inhibitors
US9586957B2 (en) * 2013-03-27 2017-03-07 VIIV Healthcare UK (No.5) Limited 2-keto amide derivatives as HIV attachment inhibitors

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FR6253M (forum.php) 1968-08-19
CH505824A (de) 1971-04-15
DE1620224A1 (de) 1970-02-12
GB1167562A (en) 1969-10-15
SE312556B (forum.php) 1969-07-21
GB1167563A (en) 1969-10-15
NL6615028A (forum.php) 1967-04-24
US3642803A (en) 1972-02-15
FR1602626A (forum.php) 1971-01-04

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