WO1996005187A1 - (4-(3-aminomethylphenyl)thiazol-2-yl)guanidines utilisees comme antagonistes des recepteurs h2 - Google Patents

(4-(3-aminomethylphenyl)thiazol-2-yl)guanidines utilisees comme antagonistes des recepteurs h2 Download PDF

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Publication number
WO1996005187A1
WO1996005187A1 PCT/JP1995/001596 JP9501596W WO9605187A1 WO 1996005187 A1 WO1996005187 A1 WO 1996005187A1 JP 9501596 W JP9501596 W JP 9501596W WO 9605187 A1 WO9605187 A1 WO 9605187A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
compound
phenyl
alkoxy
salt
Prior art date
Application number
PCT/JP1995/001596
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English (en)
Inventor
Yousuke Katsura
Tetsuo Tomishi
Shigetaka Nishino
Mitsuko Ohno
Original Assignee
Fujisawa Pharmaceutical Co., Ltd.
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 Fujisawa Pharmaceutical Co., Ltd. filed Critical Fujisawa Pharmaceutical Co., Ltd.
Priority to JP8507193A priority Critical patent/JP2000504305A/ja
Priority to AU31929/95A priority patent/AU3192995A/en
Publication of WO1996005187A1 publication Critical patent/WO1996005187A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/44—Acylated amino or imino radicals
    • C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • This invention relates to NEW COMPOUNDS and pharmaceutically acceptable salts thereof which are useful as a medicament.
  • This invention relates to new compounds and pharmaceutically acceptable salts thereof.
  • One object of this invention is to provide new thiazole derivatives and pharmaceutically acceptable salts thereof which possess antiulcer activity, r ⁇ -receptor antagonism and antimicrobial activity against pathogenic microorganisms such as Helicobacter pylori.
  • Another object of this invention is to provide processes for the preparation of said thiazole derivatives and salt thereof.
  • a further object of this invention is to provide a pharmaceutical composition comprising, as an active ingredient, said thiazole derivatives of pharmaceutically acceptable salts thereof.
  • Still further object of this invention is to provide a method for the prophylactic or therapeutic treatment of ulcer in human being or animals.
  • the thiazole derivatives of this invention are new and can be represented by the following general formula (I) :
  • R 1 is lower alkoxy, lower alkoxy(lower) alkyl, cyano (lower)alkyl, phenyl, phenyl (lower)alkyl,
  • R is hydrogen, lower alkanoyl or carbamoyl.
  • the object compound (I) or a salt thereof can be prepared by processes as illustrated in the following reaction schemes.
  • R and R 2 are each as defined above, R 3 is lower alkyl, and X is a leaving group.
  • Suitable pharmaceutically acceptable salts of the object compound (I) are conventional non-toxic salts and may include a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt; a salt with an organic base, for example, an organic amine salt (e.g., triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, hydriodide, sulfate, phosphate, etc.) ; an organic carboxylic or sulfonic acid addition salt (e.g., formate, acetate, trifluor
  • lower is used to intend a group having 1 to 6 carbon atom(s), unless otherwise provided.
  • lower alkyl and “lower alkyl moiety” in the terms “lower alkoxy (lower) alkyl", “cyano (lower) alkyl”, “phenyl (lower) alkyl”, “ [2- (lower) alkoxyphenyl] (lower) - alkyl”, “diphenyl (lower) alkyl”, “phenoxy(lower) alkyl”, “phenyl (lower) alkoxy(lower) alkyl”,
  • cyclo (lower) alkenyl (lower) alkyl may include straight or branched one having 1 to 6 carbon atom(s), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-pentyl, hexyl, and the like, and in which more preferable example may be C -C ⁇ alkyl.
  • lower alkoxy and “lower alkoxy moiety” in the terms” lower alkoxy (lower) alkyl", “ [2- (lower) alkoxyphenyl] (lower) alkyl” and
  • phenyl (lower) alkoxy (lower) alkyl may include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy, t-pentyloxy, hexyloxy and the like.
  • Suitable "cyclo (lower) alkenyl moiety" in the term “cyclo (lower) alkenyl (lower) alkyl” may include cyclohexenyl, cyclohexadienyl and the like.
  • Suitable "halogen” may include fluorine, bromine, chlorine and iodine.
  • Suitable “leaving group” may include acid residue, lower alkoxy as exemplified above, and the like.
  • Suitable "acid residue” may include halogen as exemplified above, acyloxy and the like.
  • Suitable “protected amino” may include acylamino or an amino group substituted by a conventional protecting group such as mono (or di or tri) aryl (lower) alkyl, for example, mono (or di or tri)phenyl (lower) alkyl (e.g., benzyl, trityl, etc. ) or the like.
  • a conventional protecting group such as mono (or di or tri) aryl (lower) alkyl, for example, mono (or di or tri)phenyl (lower) alkyl (e.g., benzyl, trityl, etc. ) or the like.
  • acyl and “acyl moiety” in the terms “acylammo” and “acyloxy” may include carbamoyl, aliphatic acyl group and acyl group containing an aromatic ring, w ⁇ ich is referred to as aromatic acyl, or heterocyclic ring, which is referred to as heterocyclic acyl.
  • Suitable example of said acyl may be illustrated as follows :
  • Aliphatic acyl such as lower or higher alkanoyl (e.g., formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2, 2-d ⁇ methylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, icosanoyi, etc.
  • alkanoyl e.g., formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2, 2-d ⁇ methylpropanoyl
  • lower or higher alkoxycarbonyl e.g., methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-pentyloxycarbonyl, heptyloxycarbonyl, etc.
  • lower or higher alkylsulfonyl e.g., methylsulfonyl, ethylsulfonyl, etc.
  • lower or higher alkoxysulfonyl e.g., methoxysulfonyl, ethoxysulfonyl, etc.
  • cyclo (lower) alkylcarbonyl e.g., cyclopentylcarbonyl, cyclohexylcarbonyl, etc.
  • Aromatic acyl such as aroyl (e.g., benzoyl, toluoyl, naphthoyl, etc.); ar (lower) alkanoyl [e.g., phenyl (lower) alkanoyl (e.g., phenylacetyl, phenylpropanoyl, phenylbutanoyl, phenylisobutanoyl, phenylpent
  • heterocyclic acyl such as heterocycliccarbonyl; heterocyclic(lower)alkanoyl (e.g., heterocyclicacetyl, heterocyclicpropanoyl, heterocyclicbutanoyl, heterocyclicpentanoyl, heterocyclichexanoyl, etc.); heterocyclic (lower) alkenoyl (e.g., heterocyclicpropenoyl, heterocyclicbutenoyl, heterocyclicpentenoyl, heterocyclichexenoyl, etc.); heterocyclicglyoxyloyl; or the like; in which suitable "heterocyclic moiety" in the terms "heterocycliccarbonyl", “heterocyclic(lower) alkanoyl", heterocyclic(lower) alkeno
  • heterocyclic group may be heterocyclic group such as unsaturated 3 to 8-membered (more preferably 5 or 6- membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolyl, pyrrolmyl, lmidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1, 2, -triazolyl, 1H-1,2,3- triazolyl, 2H-1, 2, 3-triazolyl, etc.), tetrazolyl (e.g., 1H- tetrazolyl, 2H-tetrazolyl, etc.), etc.; saturated 3 to 8-membered (more preferably 5 or 6- membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s), for example, pyrrolidiny
  • Suitable "lower alkanoyl” may include for yl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2- dimethylpropanoyl, hexanoyl and the like.
  • object compound (I) may include one or more stereoisomer (s) due to asymmetric carbon atom(s) and double bond(s) and all such isomers and mixture thereof are included within the scope of this invention.
  • the tautomeric forms of the object compound (I) are clearly included within the scope of the present invention.
  • the object and starting compounds including the group of such tautomeric isomers are represented by using one of the expressions therefor, that is the formula :
  • the compound (I) or a salt thereof can be prepared by reacting the compound (II) or a salt thereof with the compound (III) or a salt thereof. This reaction is usually carried out in a solvent such as water, alcohol (e.g., methanol, ethanol, etc.), benzene, N, -dimethylformamide, tetrahydrofuran, toluene, methylene chloride, ethylene dichloride, chloroform, dioxane, diethyl ether or any other solvents which do not adversely affect the reaction, or the mixture thereof.
  • a solvent such as water, alcohol (e.g., methanol, ethanol, etc.), benzene, N, -dimethylformamide, tetrahydrofuran, toluene, methylene chloride, ethylene dichloride, chloroform, dioxane, diethyl ether or any other solvents which do not adversely affect the reaction, or the mixture thereof.
  • the reaction temperature is not critical and the reaction is usually carried out under warming to heating.
  • the starting compound when in liquid, it can be used also as a solvent.
  • the compound (I) or a salt thereof can be prepared by reacting the compound (IV) or a salt thereof with the compound (V) or a salt thereof.
  • This reaction is usually carried out in a solvent such as water, alcohol (e.g., methanol, ethanol, etc.), benzene, N,N-dimethylformamide, tetrahydrofuran, toluene, methylene chloride, ethylene dichloride, chloroform, dioxane, diethyl ether or any other solvents which do not adversely affect the reaction, or the mixture thereof.
  • the reaction temperature is not critical and the reaction is usually carried out under warming to heating.
  • the reaction may be also carried out in the presence of an inorganic or an organic base such as an alkali metal (e.g., sodium, potassium, etc.), an alkali metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, etc.), an alkali metal hydrogencarbonate (e.g., sodium hydrogencarbonate, potassium hydrogencarbonate, etc.j, alkali metal carbonate (e.g.
  • an alkali metal e.g., sodium, potassium, etc.
  • an alkali metal hydroxide e.g., sodium hydroxide, potassium hydroxide, etc.
  • an alkali metal hydrogencarbonate e.g., sodium hydrogencarbonate, potassium hydrogencarbonate, etc.j
  • alkali metal carbonate e.g.
  • alkali metal hydride e.g., sodium hydride, etc.
  • alkali metal (lower) alkoxide e.g. sodium methoxide, sodium ethoxide, etc.
  • pyridme lutidine, picoline, dimethylaminopyridine, N- (lower) alkylmorpholme, N,N- di (lower) alkylbenzylamme, N,N-di (lower) alkylaniline or the like.
  • the new thiazole derivatives (I) and pharmaceutically acceptable salts thereof possess antiulcer activity, H 2 ⁇ receptor antagonism, and especially antimicrobial activity against pathogenic microorganisms such as Helicobacter pylori, and are useful for a prophylactic or therapeutic treatment of gastritis, ulcer (e.g. gastric ulcer, duodenal ulcer, anastomotic ulcer, etc.), Zollmger-Ellison Syndrome, reflux esophagitis, upper gastrointestinal bleeding, and the like.
  • Test A H 2 -receptor antagonism in isolated guinea-pig atrium
  • the atrial strip isolated from guinea-pig was suspended under an initial tension 0.3 to 0.6 g in an organ bath containing Tyrode solution at 30°C, aerated 95% 0 2 -
  • the beating rate and amplitude of contraction of the atrium were recorded by means of a transducer and a polygraph. Histamine (1 x 10 ⁇ 6 g/ml) was added to the bathing fluid and the increase in beating rate after dosing was measured. Addition of test compound (1 x 10 -6 g/ml) was made 30 minutes after washing out histamine. Inhibitory effect of test compound was calculated by comparing histamine-induced increases in beating rate before and 30 minutes after dosing with the test compound.
  • Test B in vitro Antimicrobial Activities
  • Incubation was carried out in an atmosphere of 10 r a co 2 .
  • MIC was read after incubation as the lowest Test compound concentration that inhibited macroscopic colonial growth. The data shown below are mean MIC against clinical isolated.
  • the object compound (I) or its pharmaceutically acceptable salts can usually be administered to mammals including human being in the form of a conventional pharmaceutical composition such as oral dosage form (e.g., capsule, micro-capsule, tablet, granule, powder, troche, syrup, aerosol, inhalation, suspension, emulsion, etc.), injection dosage form or suppository, or the like.
  • oral dosage form e.g., capsule, micro-capsule, tablet, granule, powder, troche, syrup, aerosol, inhalation, suspension, emulsion, etc.
  • injection dosage form or suppository or the like.
  • the pharmaceutical composition of this invention can contain various organic or inorganic carrier materials, which are conventional used for pharmaceutical purpose, such as excipient (e.g. sucrose, starch, mannit, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, calcium carbonate, etc.), binding agent (e.g. cellulose, methyl cellulose, hydroxypropylcellulose, polypropylpyrrolidone, gelatin, gum arabic, polyethyleneglycol, sucrose, starch, etc.), disintegrator (e.g.
  • excipient e.g. sucrose, starch, mannit, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, calcium carbonate, etc.
  • binding agent e.g. cellulose, methyl cellulose, hydroxypropylcellulose, polypropylpyrrolidone, gelatin, gum arabic, polyethyleneglycol, sucrose, starch, etc.
  • disintegrator e.g
  • starch carboxymethyl cellulose, calcium salt of carboxymethyl cellulose, hydroxypropylstarch, sodium glycole-starch, sodium bicarbonate, calcium phosphate, calcium citrate, etc.), lubricant (e.g. magnesium stearate, talc, sodium laurylsulfate, etc.), flavoring agent (e.g. citric acid, menthol, glycine, orange powders, etc.), preservative (e.g. sodium benzoate, sodium bisulfite, methylparaben, propylparaben, etc.), stabilizer (e.g. citric acid, sodium citrate, acetic acid, etc.), suspending agent (e.g.
  • methyl cellulose methyl cellulose, polyvinylpyrrolidone, aluminum stearate, etc.
  • dispersing agent e.g. water
  • aqueous diluting agent e.g. water
  • base wax e.g. cacao butter, polyethyleneglycol, white petrolatum, etc.
  • the dosage of the compound (I) will vary depending upon the age and condition of the patient, an average single dose of about 0.1 mg, 1 mg, 10 mg, 50 mg,
  • 100 mg, 250 mg, 500 mg and 1000 mg of the compound (I) may be effective for treating ulcer.
  • amounts between 0.1 g/body and about 1,000 mg/body may be administered per day.
  • Preferred embodiments of the object compound (I) are as follows.
  • R 1 is lower alkoxy, ethoxy(lower) alkyl, cyano (lower) alkyl, phenyl, phenyl (lower) alkyl,
  • Example 7 A solution of 3- (acetylaminomethyl) acetophenone (700 mg) and bromine (610 mg) in dioxane (10 ml) was stirred at room temperature for 5 hours. Methanol (20 ml), [ (phenylamino) (aminomethylene] thiourea (700 mg) and potassium carbonate (l.llg) were added to the reaction mixture. The mixture was heated at 55°C for 2 hours. The solvent was removed under reduced pressureand the residue was dissolved in a mixtue of water (60 ml) and tetrahydrofuran (40 ml) . The mixture was adjusted to pH 10 with 30% potassium carbonate solution and then was. extracted with ethyl acetate (150 ml) .

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

De nouveaux composés, ou un de leurs sels pharmacologiquement acceptables, sont utiles comme médicaments et correspondent à la formule (I), où R1 représente alcoxy inférieur, alcoxy inférieur alkyle(inférieur), cyanoalkyle(inférieur), phényle, phénylalkyle(inférieur), [2-alcoxyphényle(inférieur)]alkyle(inférieur), diphénylalkyle(inférieur), phénoxyalkyle(inférieur), phényl(inférieur)alcoxy(inférieur)alkyle, cycloalcényle(inférieur)alkyle(inférieur), aminoalkyle(inférieur)protégé ou adamantyloxyalkyle(inférieur), et R2 représente hydrogène, ou alcanoyle ou carbamoyle inférieur.
PCT/JP1995/001596 1994-08-15 1995-08-09 (4-(3-aminomethylphenyl)thiazol-2-yl)guanidines utilisees comme antagonistes des recepteurs h2 WO1996005187A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP8507193A JP2000504305A (ja) 1994-08-15 1995-08-09 Ｈ▲下２▼受容体拮抗剤としての（４−（３−アミノメチルフェニル）チアゾール−２−イル）グアニジン類
AU31929/95A AU3192995A (en) 1994-08-15 1995-08-09 (4-(3-aminomethylphenyl)thiazol-2-yl)-guanidines as h2-receptor antagonists

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9416459.7 1994-08-15
GB9416459A GB9416459D0 (en) 1994-08-15 1994-08-15 New compounds

Publications (1)

Publication Number Publication Date
WO1996005187A1 true WO1996005187A1 (fr) 1996-02-22

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JP (1) JP2000504305A (fr)
AU (1) AU3192995A (fr)
GB (1) GB9416459D0 (fr)
WO (1) WO1996005187A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998050373A1 (fr) * 1997-05-06 1998-11-12 Bayer Aktiengesellschaft Aminothiazoles substitues et leur utilisation comme principes actifs antimicrobiens
WO2005082871A3 (fr) * 2004-02-19 2005-11-10 Abbott Gmbh & Co Kg Composes de guanidine et leur utilisation comme elements de liaison pour les recepteurs 5-ht5

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0003640A2 (fr) * 1978-01-18 1979-08-22 Imperial Chemical Industries Plc Dérivés de guanidine à activité antisécrétive de l'acide gastrique, procédés pour leur préparation et compositions pharmaceutiques les contenant
JPS59225172A (ja) * 1983-06-03 1984-12-18 Yamanouchi Pharmaceut Co Ltd 新規グアニジノチアゾ−ル誘導体及びその製法
EP0545376A1 (fr) * 1991-12-06 1993-06-09 Fujisawa Pharmaceutical Co., Ltd. Dérivés de guanidino thiazoles et leur utilisation comme antagonistes de recepteurs-H2

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0003640A2 (fr) * 1978-01-18 1979-08-22 Imperial Chemical Industries Plc Dérivés de guanidine à activité antisécrétive de l'acide gastrique, procédés pour leur préparation et compositions pharmaceutiques les contenant
JPS59225172A (ja) * 1983-06-03 1984-12-18 Yamanouchi Pharmaceut Co Ltd 新規グアニジノチアゾ−ル誘導体及びその製法
EP0545376A1 (fr) * 1991-12-06 1993-06-09 Fujisawa Pharmaceutical Co., Ltd. Dérivés de guanidino thiazoles et leur utilisation comme antagonistes de recepteurs-H2

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 8505, Derwent World Patents Index; AN 85-029005 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998050373A1 (fr) * 1997-05-06 1998-11-12 Bayer Aktiengesellschaft Aminothiazoles substitues et leur utilisation comme principes actifs antimicrobiens
WO2005082871A3 (fr) * 2004-02-19 2005-11-10 Abbott Gmbh & Co Kg Composes de guanidine et leur utilisation comme elements de liaison pour les recepteurs 5-ht5
EP2366697A1 (fr) 2004-02-19 2011-09-21 Abbott GmbH & Co. KG Composés de guanidine et leur utilisation comme partenaire de liaison pour récepteurs 5-HT5
EP2366392A1 (fr) 2004-02-19 2011-09-21 Abbott GmbH & Co. KG Composés de guanidine et leur utilisation comme partenaire de liaison pour récepteurs 5-HT5
EP2380885A1 (fr) * 2004-02-19 2011-10-26 Abbott GmbH & Co. KG Composés de guanidine et leur utilisation comme partenaire de liaison pour récepteurs 5-HT5
US8431604B2 (en) 2004-02-19 2013-04-30 Abbott Gmbh & Co. Kg Guanidine compounds, and use thereof as binding partners for 5-HT5 receptors
US8481576B2 (en) 2004-02-19 2013-07-09 Abbott Gmbh & Co. Kg Guanidine compounds, and use thereof as binding partners for 5-HT5 receptors
US9475782B2 (en) 2004-02-19 2016-10-25 AbbVie Deutschland GmbH & Co. KG Guanidine compounds, and use thereof as binding partners for 5-HT5 receptors

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JP2000504305A (ja) 2000-04-11
GB9416459D0 (en) 1994-10-05
AU3192995A (en) 1996-03-07

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