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WO1995023137A1 - Derives amides d'acide acetique et leur procede de preparation - Google Patents

Derives amides d'acide acetique et leur procede de preparation Download PDF

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Publication number
WO1995023137A1
WO1995023137A1 PCT/HU1995/000003 HU9500003W WO9523137A1 WO 1995023137 A1 WO1995023137 A1 WO 1995023137A1 HU 9500003 W HU9500003 W HU 9500003W WO 9523137 A1 WO9523137 A1 WO 9523137A1
Authority
WO
WIPO (PCT)
Prior art keywords
general formula
acetamide
tetrahydroacridin
piperazin
pharmaceutically acceptable
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.)
Ceased
Application number
PCT/HU1995/000003
Other languages
English (en)
Inventor
Józsefné REITER
Zoltán Budai
Gáborné TAKÁTS
Tibor Mezei
Gábor BLASKÓ
Gyula Simig
András Egyed
E. Szilveszter Vizi
Márton Fekete
Katalin Szemerédi
István Gyertyán
István Gacsályi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Egyt Gyogyszervegyeszeti Gyar
Egis Pharmaceuticals PLC
Original Assignee
Egyt Gyogyszervegyeszeti Gyar
Egis Pharmaceuticals PLC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Egyt Gyogyszervegyeszeti Gyar, Egis Pharmaceuticals PLC filed Critical Egyt Gyogyszervegyeszeti Gyar
Priority to KR1019960704569A priority Critical patent/KR970701177A/ko
Priority to JP7522225A priority patent/JPH09512784A/ja
Priority to EP95909911A priority patent/EP0746549A1/fr
Priority to AU29728/95A priority patent/AU2972895A/en
Publication of WO1995023137A1 publication Critical patent/WO1995023137A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C07D219/10—Nitrogen atoms attached in position 9
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • This invention relates to new acetic acid derivatives, a process for the preparation thereof, pharmaceutical compositions comprising the same, to the use of the said acetic acid amide derivatives for the treatment of diseases and for the preparation of pharmaceutical compositions suitable for the treatment of diseases.
  • B represents piperazino, 8-azaspiro[4,5]decane-7,9-dion-8-yl or 2-(1,2,4-triazolo[4,3-a]pyridyl-3(2H)-on-2-yl) optionally carrying an aryl, aralkyl or heteroaryl substituent.
  • the invention encompasses the pharmaceutically acceptable acid-addition salts of the compounds of general formula (I), too.
  • the new compounds according to the invention posses valuable pharmaceutical properties, more specifically they are suitable for the treatment of Alzheimer's disease. At the same time they exert only a few side-effects.
  • Senile dementia is a common diagnosis characterized by the deterioration of cognitive functions and of adjustment to situations in everyday life.
  • the neuropathological basis thereof is constituted by the plaques decreasing cerebral activity described by Alois Alzheimer in 1906. These symptoms are called Alzheimer's disease.
  • the Alzheimer's disease is, to our knowledge, incurable. So far the following methods have been used for the treatment thereof:
  • tacrine 1,2,3,4-tetrahydro-9-acridinamine
  • the aim of the present invention is to eliminate the above-mentioned drawbacks of tacrine and to provide new compounds which possess the reversible cholinesterase-inhibiting effect of tacrine but are devoid of its undesirable side-effects.
  • aryl group used throughout the specification relates to the phenyl and naphthyl groups that may optionally carry substituents such as lower alkyl, lower alkoxy, hydroxy, nitro, amino or halogen.
  • lower covers groups having 1 to 7, preferably 1 to 4, carbon atom(s).
  • lower alkyl or “lower alkoxy” refers to straight or branched chained alkyl or alkoxy groups (e.g. methyl, ethyl, propyl, ethoxy, methoxy, isopropoxy, etc.).
  • halogen atom encompasses the fluorine, chlorine, bromine and iodine atoms.
  • aralkyl covers lower alkyl groups carrying one or two aryl substituent(s) (e.g. benzyl, beta-phenylethyl, ß,ß-diphenylethyl, etc.).
  • heteroaryl relates to heteroaromatic groups comprising one or two ring(s) and containing one or two nitrogen, oxygen and/or sulfur atom(s) (e.g. pyridyl, pyrimidinyl, thiazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, etc.).
  • the aralkyl and heteroaryl groups may carry one or two substituent(s) enumerated in connection with the aryl group.
  • Preferred representatives of the compounds of general formula (I) are those wherein B stands for piperazino optionally carrying a phenyl or benzyl substituent optionally substituted by halogen, pyridyl or pyrimidinyl, and pharmaceutically acceptable acid-addition salts thereof.
  • the pharmaceutically acceptable acid-addition salts of the compounds of general formula (I) can be formed with inorganic or organic acids (e.g. hydrohalides such as hydrochlorides or hydrobromides; sulfates, nitrates, phosphates, acetates, propionates, maleates, fumarates, lactates, succinates, ascorbinates, tartrates, etc.) or with sulfonic acids (e.g. benzenesulfonates, methanesulfonates, p-toluenesulfonates).
  • inorganic or organic acids e.g. hydrohalides such as hydrochlorides or hydrobromides
  • sulfonic acids e.g. benzenesulfon
  • Hlg stands for chlorine, bromine or iodine, with a compound of general formula (V),
  • reaction of the compounds of general formulae (II) and (V) is carried out in a known manner.
  • the reaction is preferably performed in an inert organic solvent.
  • organic solvents particularly aliphatic alcohols (e.g. ethanol or isopropanol), aromatic hydrocarbons (e.g. benzene, toluene or xylene) or ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran or dioxane) can be used.
  • the reaction is carried out in the presence of a basic condensing agent.
  • organic bases e.g.
  • pyridine, picoline, lutidine or triethylamine) or alkali carbonates e.g. sodium carbonate or potassium carbonate
  • the reaction is carried out at a temperature between 0 °C and 130 °C, preferably at a temperature between 40 °C and 90 °C.
  • an amino compound of formula (III) is reacted with a compound of general formula (IV) by methods known per se .
  • the compounds of general formula (IV) used as starting substances may be, depending on the meaning of X, free carboxylic acids, acid halides, esters, acid anhydrides or mixed anhydrides. It is preferable to apply carboxylic acids of general formula (IV), wherein X represents hydroxy, acid halides (X stands for chlorine or bromine) or esters (X stands for lower alkoxy such as methoxy or ethoxy).
  • the reaction of the compounds of general formulae (III) and (IV) can be carried out in an inert solvent. As reaction medium the solvents mentioned in connection with process variant a) can be used. The reaction is preferably performed under heating.
  • the compounds of general formula (I) can be converted into pharmaceutically acceptable acid-addition salts with the appropriate acids by methods known per se , or can be liberated from their salts in a known manner.
  • the 9-amino-1,2,3,4-tetrahydroacridine of general formula (III) used as starting substance for the process according to the invention can be prepared as specified in J. Soc. Chem. Ind. 64, 16972 (1945).
  • the acetamide derivatives of general formula (II) can be produced as specified in Chem. Listy 51, 1906-8 (1957) and the substituted acetic acid derivatives of general formula (IV) can be prepared as described e.g. in Acta Univ. Szegediensis, Acta Phys. et Chem. 6 , 80-6, 1960 or Acta Pharm. Hung. 31, 113-21 (1961) or in the U.S. patent specification No. 2,568,141.
  • compositions comprising as active ingreident a compound of general formula (I) or a pharmaceutically acceptable acid-addition salt thereof in admixture with suitable inert solid or liquid pharmaceutical carriers.
  • compositions of the present invention can be prepared by methods known per se by admixing the active ingredient with suitable inert solid or liquid carriers and bringing the mixture to galenic form.
  • compositions of the present invention may be suitable for oral (e.g. tablet, pill, coated pill, dragee, capsule, drop, solution or suspension), parenteral (e.g. injection solution) or rectal (e.g. suppository) administration.
  • oral e.g. tablet, pill, coated pill, dragee, capsule, drop, solution or suspension
  • parenteral e.g. injection solution
  • rectal e.g. suppository
  • the solid pharmaceutical compositions may comprise usual additives (such as lubricants, stabilizers, emulsifiers, disintegrating agents, salts or buffers causing the change of osmotic pressure).
  • the capsules may be soft or hard gelatin capsules.
  • the suppositories may contain usual synthetic or natural base materials (e.g. cocoa butter, fatty acid triglycerides, Witepsol, etc.).
  • the injections are usually aqueous solutions which can be isotonized with sodium chloride.
  • the daily dose of the compounds of general formula (I) can vary within wide ranges depending on several factors, e.g. on the activity of the active ingredient, the patient's condition and age, the severity of the disease, etc.
  • the oral dose is generally 1 to 1000 mg/day, while the parenteral dose is generally 0.1 to 100 mg/day, preferably 0.1 to 50 mg/day.
  • the daily dose of the compounds of the present invention may be administered at once or in several (e.g. three) portions with appropriate intervals. Determination of the proper dosage for a particular situation is within the skill of the art.
  • a process for the preparation of pharmaceutical compositions which comprises admixing a compound of general formula (I) or a pharmaceutically acceptable acid-addition salt thereof with suitable inert solid or liquid therapeutical carriers.
  • a method for the treatment of Alzheimer's disease which comprises administering to a patient an effective amount of a compound of general formula (I) or a pharmaceutically acceptable acid-addition salt thereof.
  • the new compounds of general formula (I) are remarkable for their low toxicity and selective cholinesterase-inhibiting effect.
  • the ratio of the inhibitions exerted on the two kinds of enzyme provides information on the specificity of the inhibition. These enzymes are much more liable to split thiocholine esters than the physiological substrates thereof. Thiocholine formed as a consequence of the enzyme activity can be determined by photometry when reacted with dithio-bis-nitrobenzoic acid (DTNB).
  • DTNB dithio-bis-nitrobenzoic acid
  • Tacrine was used as reference substance.
  • the inhibitory activity of the test compounds at a concentration of 10 -5 M (inhibition %) and ID 50 values are shown in the following Tables.
  • Example 1 One proceeds as specified in Example 1 except that 1-(2-pyridinyl)-piperazine (7.18 g, 0.044 mole) is used as amine.
  • Example 1 One proceeds as specified in Example 1 except that the reaction is carried out in a 20:1 mixture of isopropanol and dimethylformamide and 5.94 g (0.044 mole) of 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one are used as amine.
  • Tablet comprising 25 mg of active ingredient Composition of one tablet is as follows :
  • Active ingredient 25 0 mg
  • the tablet is prepared as follows:
  • the active ingredient and the corn starch are admixed, then wetted with 10-15 % by weight of aqueous polyvinylpyrrolidone solution and the mixture is granulated, then dried at a temperature of 40 to 50 °C.
  • the dry granules are rubbed through a sieve, mixed with talc and magnesium stearate and tablets are prepared from the mixture.
  • the weight of one tablet is 300 mg.
  • Tablet comprising 250 mg of active ingredient Composition of one tablet is as follows :
  • Active ingredient 250 0 mg
  • the tablet is prepared as follows:
  • the active ingredient, the lactose and the corn starch are wetted and mixed, granulated and dried at a temperature of 40 to 50 °C.
  • the dry granules are rubbed through a sieve, mixed with magnesium stearate and tablets are formed.
  • the weight of one tablet is 600.0 mg.
  • Dragee comprising 25 mg of active ingredient
  • the composition of one dragee core is as follows:
  • the dragee is prepared as follows:
  • the active ingredient and the corn starch are mixed, wetted with 10 % by weight aqueous gelatin solution, granules are formed from the wet mixture and the granules are dried at a temperature of 40 to 50 °C.
  • the dry granules are rubbed through a sieve, homogenized with talc and magnesium stearate and dragee cores of 300.0 mg are compressed from the mixture.
  • composition of one dragee core is as follows:
  • the granules are prepared as described in Example 10.
  • the weight of one dragee core is 150.0 mg.
  • the dragee cores are coated with a layer containing sugar and talc in a manner known per se .
  • the dragee thus obtained is painted with non-toxic food paint to the desired colour and polished with bee-wax.
  • Gelatin capsule comprising 5.0 mg og active ingredient
  • the composition of one gelatine capsule is as follows:
  • the components are homogenized and filled into gelatin capsules of suitable size.
  • Gelatine capsule comprising 25.0 mg of active ingredient
  • the composition of one gelatin capsule is as follows: Active ingredient 25.0 mg
  • Example 14 The ingredients are homogenized and filled into gelatin capsules of suitable size.
  • Example 14 The ingredients are homogenized and filled into gelatin capsules of suitable size.
  • Gelatine capsule comprising 50 mg of active ingredient
  • composition of one gelatin capsule is as follows:
  • Example 15 The ingredients are homogenized and filled into gelatin capsules of suitable size.
  • Example 15 The ingredients are homogenized and filled into gelatin capsules of suitable size.
  • Gelatine capsule comprising 250 mg of active ingredient
  • composition of one gelatin capsule is as follows : Active ingredient 250. 0 mg
  • composition of one ampoule is as follows:
  • the active ingredient and sodium chloride are dissolved in the necessary amount of twice-distilled water suitable for making injections .
  • the solution is filtered, filled into ampoules and sterilized.
  • composition of one ampoule is as follows :
  • Suppository comprising 250.0 mg of active ingredient
  • composition of one suppository is as follows:
  • the fatty acid glyceride is melted, the active ingredient is homogenized, then poured into a mould.
  • the sorbitol, the active ingredient, the citric acid and the sodium citrate are dissolved in the aqueous solution of propylene glycol, then after dissolution of the solid materials the flavourant is added.
  • the solution is filtered and filled into flasks supplied with a drop-dispenser.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hospice & Palliative Care (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Psychiatry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Nouveaux dérivés d'acide acétique, leur procédé de préparation, compositions pharmaceutiques les comportant, et utilisation desdits dérivés amidés d'acide acétique dans le traitement de maladies et dans la préparation de compositions pharmaceutiques convenant au traitement de maladies. Ces nouveaux composés peuvent être caractérisés par la formule générale (I), dans laquelle R représente hydrogène et B représente pipérazino, 8-azaspiro[4,5]décane-7,9-dion-8-yle ou 2-(1,2,4-triazolo[4,3-a]pyridyl-3(2H)-on-2-yle) portant éventuellement un substituant aryle, aralkyle ou hétéroaryle. En outre, ils ont de précieuses propriétés pharmaceutiques et ils conviennent au traitement de la maladie d'Alzheimer.
PCT/HU1995/000003 1994-02-23 1995-02-22 Derives amides d'acide acetique et leur procede de preparation Ceased WO1995023137A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
KR1019960704569A KR970701177A (ko) 1994-02-23 1995-02-22 아세트산 아미드 유도체 및 그것의 제조 방법(amide derivatives and process for the preparation thereof)
JP7522225A JPH09512784A (ja) 1994-02-23 1995-02-22 酢酸アミド誘導体及びその製造方法
EP95909911A EP0746549A1 (fr) 1994-02-23 1995-02-22 Derives amides d'acide acetique et leur procede de preparation
AU29728/95A AU2972895A (en) 1994-02-23 1995-02-22 Acetic acid amide derivatives and process for the preparation thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HUP9400517 1994-02-23
HU9400517A HU213107B (en) 1994-02-23 1994-02-23 Process for producing acetic acid derivatives and pharmaceutical compositions containing them

Publications (1)

Publication Number Publication Date
WO1995023137A1 true WO1995023137A1 (fr) 1995-08-31

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ID=10984860

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1995/000003 Ceased WO1995023137A1 (fr) 1994-02-23 1995-02-22 Derives amides d'acide acetique et leur procede de preparation

Country Status (6)

Country Link
EP (1) EP0746549A1 (fr)
JP (1) JPH09512784A (fr)
KR (1) KR970701177A (fr)
AU (1) AU2972895A (fr)
HU (1) HU213107B (fr)
WO (1) WO1995023137A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1415651A4 (fr) * 2001-08-06 2005-11-09 Mitsubishi Pharma Corp Compositions prophylactiques/therapeutiques destinees a la neuropathie cholinergique
US7183413B2 (en) 2003-04-11 2007-02-27 Taigen Biotechnology Aminoquinoline compounds
US7378524B2 (en) 2003-04-11 2008-05-27 Taigen Biotechnology Co., Ltd. Aminoquinoline compounds
US7538114B2 (en) 2006-06-28 2009-05-26 Amgen Inc. Glycine transporter-1 inhibitors
EP1598355A4 (fr) * 2003-01-08 2010-01-27 Mitsubishi Tanabe Pharma Corp Agent therapeutique pour la schizophrenie
US7910739B2 (en) 2003-07-09 2011-03-22 Noscira, S.A. Acetylcholinesterase dual inhibitors
CN105367553A (zh) * 2015-12-04 2016-03-02 广东工业大学 一种他克林-8-羟（胺）基喹啉衍生物及其应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0319429A2 (fr) * 1987-12-03 1989-06-07 Mitsubishi Kasei Corporation Dérivés de la 9-(acylamino)tétrahydroacridine et agents pour l'amélioration de la mémoire les contenant comme ingrédient
EP0411534A2 (fr) * 1989-07-31 1991-02-06 Warner-Lambert Company Dérivés de 1,2,3,4-tétrahydro-9-acridinamine
WO1991001974A1 (fr) * 1989-08-01 1991-02-21 Trifree Limited Derives d'acridine

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0319429A2 (fr) * 1987-12-03 1989-06-07 Mitsubishi Kasei Corporation Dérivés de la 9-(acylamino)tétrahydroacridine et agents pour l'amélioration de la mémoire les contenant comme ingrédient
EP0411534A2 (fr) * 1989-07-31 1991-02-06 Warner-Lambert Company Dérivés de 1,2,3,4-tétrahydro-9-acridinamine
WO1991001974A1 (fr) * 1989-08-01 1991-02-21 Trifree Limited Derives d'acridine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 112, No. 21, issued 21 May 1990, (Columbus, Ohio, U.S.A.), "Synthesis and Biological Activity of 9-[N,N-Dialkylaminoacetyl)Amino]-1,2,3,4-Tetrahydroacridines", DONTSOVA et al.; & KHIM. -FARM. ZH 1989, page 55, Abstract No. 191 729h. *
CHEMICAL ABSTRACTS, Vol. 115, No. 7, issued 19 August 1991, (Columbus, Ohio, U.S.A.), "Preparation of 9-Acylaminotetrahydroacridine Derivatives as Memory Improvers", MORITA et al.; & JPN KOKAI TOKKYO KOHO JP,page 777, Abstract No. 71 418w. *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1415651A4 (fr) * 2001-08-06 2005-11-09 Mitsubishi Pharma Corp Compositions prophylactiques/therapeutiques destinees a la neuropathie cholinergique
EP1598355A4 (fr) * 2003-01-08 2010-01-27 Mitsubishi Tanabe Pharma Corp Agent therapeutique pour la schizophrenie
US7183413B2 (en) 2003-04-11 2007-02-27 Taigen Biotechnology Aminoquinoline compounds
US7378524B2 (en) 2003-04-11 2008-05-27 Taigen Biotechnology Co., Ltd. Aminoquinoline compounds
US7910739B2 (en) 2003-07-09 2011-03-22 Noscira, S.A. Acetylcholinesterase dual inhibitors
US7538114B2 (en) 2006-06-28 2009-05-26 Amgen Inc. Glycine transporter-1 inhibitors
US8183244B2 (en) 2006-06-28 2012-05-22 Amgen Inc. Glycine transporter-1 inhibitors
US8735383B2 (en) 2006-06-28 2014-05-27 Amgen Inc. Glycine transporter-1 inhibitors
US9663476B2 (en) 2006-06-28 2017-05-30 Amgen Inc. Glycine transporter-1 inhibitors
CN105367553A (zh) * 2015-12-04 2016-03-02 广东工业大学 一种他克林-8-羟（胺）基喹啉衍生物及其应用

Also Published As

Publication number Publication date
KR970701177A (ko) 1997-03-17
EP0746549A1 (fr) 1996-12-11
JPH09512784A (ja) 1997-12-22
AU2972895A (en) 1995-09-11
HU9400517D0 (en) 1994-05-30
HUT70615A (en) 1995-10-30
HU213107B (en) 1997-02-28

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