WO1993018769A2 - Nouvelle utilisation d'un derive de quinazoline - Google Patents

Nouvelle utilisation d'un derive de quinazoline Download PDF

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Publication number
WO1993018769A2
WO1993018769A2 PCT/JP1993/000307 JP9300307W WO9318769A2 WO 1993018769 A2 WO1993018769 A2 WO 1993018769A2 JP 9300307 W JP9300307 W JP 9300307W WO 9318769 A2 WO9318769 A2 WO 9318769A2
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WO
WIPO (PCT)
Prior art keywords
alkyl
hydroxy
protected
ester
prolactin
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Application number
PCT/JP1993/000307
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English (en)
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WO1993018769A3 (fr
Inventor
Kimio Esumi
Keizo Sogabe
Original Assignee
Fujisawa Pharmaceutical Co., Ltd.
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Filing date
Publication date
Application filed by Fujisawa Pharmaceutical Co., Ltd. filed Critical Fujisawa Pharmaceutical Co., Ltd.
Publication of WO1993018769A2 publication Critical patent/WO1993018769A2/fr
Publication of WO1993018769A3 publication Critical patent/WO1993018769A3/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim

Definitions

  • the present invention relates to a new use or method of a quinazoline derivative or a pharmaceutically acceptable salt thereof.
  • cardiac hypertrophy nephropacy such as nephritis, renal failure, etc.
  • arteriosclerosis obliterans, obstructive thrombus, arterial embolus, Burger-Grutz syndrome, acrocyanosis, chilblain, frostbite, prolactin-producing ovulation disorder,
  • galactoschesia galactorrhea
  • distal hypertrophy pituitary gigantism
  • mental illness such as melancholia
  • anxiety schizophrenia, etc
  • cerebrovascular diseases such as cerebral infarction, cerebral circulation insufficiency, tachycardia accompanied by sympathetic hypertonia,
  • hyperaldosteronism diabetic complication such as diabetic hypertriglyceromia, and the like, to a method for the treatment of various diseases such as cardiac hypertrophy, nephropacy such as nephritis, renal failure, etc,
  • arteriosclerosis obliterans, obstructive thrombus, arterial embolus, Burger-Grutz syndrome, acrocyanosis, chilblain, frostbite, prolactin-producing ovulation disorder,
  • galactoschesia galactorrhea
  • distal hypertrophy pituitary gigantism
  • mental illness such as melancholia
  • anxiety schizophrenia, etc
  • cerebrovascular diseases such as cerebral infarction, cerebral circulation insufficiency, tachycardia accompanied by sympathetic hypertonia,
  • hyperaldosteronism diabetic complication such as diabetic hypertriglyceromia, and the like, which comprises
  • one object of the present invention is to provide a new use of a quinazoline derivative or a
  • obstructive thrombus arterial embolus, Burger-Grutz syndrome, acrocyanosis, chilblain, frostbite, prolactin-producing ovulation disorder, prolactin-producing pituitary tumor, puerperal galactoschesia, galactorrhea, distal hypertrophy, pituitary gigantism, mental illness such as melancholia, anxiety, schizophrenia, etc, cerebrovascular diseases such as cerebral infarction, cerebral circulation insufficiency, tachycardia accompanied by sympathetic hypertonia, hyperaldosteronism, diabetic complication such as diabetic hypertriglyceromia, and the like.
  • Another object of the present invention is to provide a new method for the treatment of various diseases such as cardiac hypertrophy, nephropacy such as nephritis, renal failure, etc, arteriosclerosis obliterans, obstructive thrombus, arterial embolus, Burger-Gnltz syndrome,
  • various diseases such as cardiac hypertrophy, nephropacy such as nephritis, renal failure, etc, arteriosclerosis obliterans, obstructive thrombus, arterial embolus, Burger-Gnltz syndrome,
  • acrocyanosis acrocyanosis, chilblain, frostbite.
  • prolactin-producing ovulation disorder prolactin-producing pituitary tumor, puerperal galactoschesia, galactorrhea, distal hypertrophy, pituitary gigantism, mental illness such as melancholia, anxiety, schizophrenia, etc, cerebrovascular diseases such as cerebral infarction, cerebral circulation insufficiency, tachycardia accompanied by sympathetic hypertonia,
  • hyperaldosteronism diabetic complication such as diabetic hypertriglyceromia, and the like, which comprises
  • the compound used in this invention is known to have dopamine receptor stimulating effects; 5-HT receptor antagonism, especially 5-HT 2 receptor antagonism; « ⁇ receptor antagonism; and the like, and to be useful as a dopamine receptor agonist; 5-HT receptor antagonist, especially 5-HT 2 receptor antagonist; ⁇ 1 receptor
  • the inventors of this invention have found that the quinazoline derivative of this invention is also useful for the treatment of various diseases such as cardiac
  • hypertrophy nephropacy such as nephritis, renal failure, etc, arteriosclerosis obliterans, obstructive thrombus, arterial embolus, Burger-Gnltz syndrome, acrocyanosis, chilblain, frostbite, prolactin-producing ovulation disorder, prolactin-producing pituitary tumor, puerperal galactoschesia, galactorrhea, distal hypertrophy, pituitary gigantism, mental illness such as melancholia, anxiety, schizophrenia, etc, cerebrovascular diseases such as cerebral infarction, cerebral circulation insufficiency, tachycardia accompanied by sympathetic hypertonia,
  • the quinazoline derivative used in this invention can be represented by the following general formula: in which R 1 and R 2 are each hydrogen, halogen, nitro, amino, protected amino, hydroxyamino, lower alkyl, hydroxy, protected hydroxy, sulfamoyl, carboxy, protected carboxy, mercapto, optionally
  • substituted heterocyclic-carbonyl optionally substituted heterocyclic- (lower)alkyl, lower alkylthio, hydroxy(lower)alkyl or protected hydroxy(lower)alkyl,
  • R 3 is aryl which may have suitable
  • A is lower alkylene
  • a salt with a base such as an inorganic base salt, 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, an organic base salt, for example, an organic amine salt (e.g. triethylamine salt, pyridine salt, picoline salt,
  • a base salt such as an inorganic base salt, 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, an organic base salt, for example, an organic amine salt (e.g. triethylamine salt, pyridine salt, picoline salt,
  • an organic base salt 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.
  • a salt with an acid such as inorganic acid addition salt (e.g.
  • hydrochloride hydrobromide, sulfate, phosphate, etc.
  • organic acid addition salt e.g. formate, acetate
  • methanesulfonate, benzenesulfonate, etc. a salt with a basic or acidic amino acid (e.g. arginine, aspartic acid, glutamic acid, etc.); and the like, particularly sulfate thereof is preferable.1
  • lower is intended to mean 1 to 6 carbon atom(s), preferably 1 to 4 carbon atom(s), unless otherwise indicated.
  • Suitable “lower alkyl” may include straight or
  • branched one such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, and the like.
  • Suitable "lower alkoxy” may include straight or branched one such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, pentyloxy, hexyloxy, and the like, in which the most preferable one may be methoxy.
  • Suitable "aryl which may have suitable substituent(s)” may include phenyl, tolyl, xylyl, cumenyl, mesithyl, naphthyl, and the like, each of which may be substituted by one or more, preferably one or two substituent(s) such as halogen (e.g. fluorine, chlorine, bromine, iodine), lower alkyl as mentioned above (e.g. methyl, etc.), and the like, in which more preferred example may be phenyl which is substituted or unsubstituted by a group consisting of halogen and lower alkyl, and the most preferred one may be phenyl, 4-chloro(or fluorophenyl and 4-tolyl.
  • Suitable "protected carboxy” may include carbamoyl, esterified carboxy wherein "esterifled carboxy” can be referred to the ones as mentioned below, and the like.
  • ester moiety of an esterified carboxy may be the ones such as lower alkyl ester (e.g.
  • methyl ester ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, t-butyl ester, pentyl ester, hexyl ester, etc.
  • suitable substituent(s) for example, lower alkanoyloxy(lower)alkyl ester [e.g. acetoxymethyl ester, propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester,
  • pivaloyloxymethyl ester pivaloyloxymethyl ester, hexanoyloxymethyl ester, 1-(or 2-)aeetoxyethyl ester, 1-(or 2- or 3-)acetoxypropyl ester, 1- (or 2- or 3- or 4-)acetoxybutyl ester, 1-(or 2- )propionyloxyethyl ester, 1-(or 2- or 3-)propionyloxypropyl ester, 1-(or 2-)butyryloxyethyl ester, 1-(or 2- )isobutyryloxyethyl ester, 1-(or 2-)pyvaloyloxyethyl ester, 1-(or 2-)hexanoyloxyethyl ester, isobutyryloxymethyl ester, 2-ethylbutyryloxymethyl ester, 3,3- dimethylbutyryloxymethyl ester, 1-(or 2-)pentanoyloxy- ethyl ester, etc.], lower alkan
  • 2-mesylethyl ester, etc. mono(or di or tri)halo-(lower)alkyl ester (e.g. 2-iodoethyl ester, 2,2,2-trichloroethyl ester, etc.); lower
  • alkoxycarbonyloxy(lower)alkyl ester e.g.
  • triphenyl(lower)alkyl ester which may have at least one suitable substituent(s) (e.g. lower alkoxy, nitro, hydroxy, lower alkyl, etc.), for example, mono- or di- or triphenyl(lower)alkyl ester which may have (lower)alkoxy [e.g. benzyl ester, benzhydryl ester, trityl ester,
  • phenethyl ester 4-methoxybenzyl ester, 3,4-dimethoxybenzyl ester, bis(methoxyphenyl)methyl ester, etc.], nitrophenyl(lower)alkyl ester (e.g. 4-nitrobenzyl ester, etc.), [hydroxy]-(lower)alkylphenyl(lower)alkyl ester (e.g. 4-hydroxy-3,5-di-t-butylbenzyl ester, etc.); aryl ester which may have at least one suitable substituent(s) (e.g.
  • phenyl ester 4-chlorophenyl ester, tolyl ester, t-butylphenyl ester, xylyl ester, mesityl ester, cumenyl ester, etc.); phthalidyl ester; and the like.
  • protected carboxy thus defined may be carbamoyl and lower alkoxycarbonyl.
  • Suitable "protected amino” may include amino protected by a conventional amino-protective group as mentioned below.
  • Suitable “amino-protective group” may include acyl such as aliphatic acyl, aromatic acyl, heterocyclic acyl and aliphatic acyl substituted with aromatic or heterocyclic group(s) derived from carboxylic, carbonic, sulfonic and carbamic acids.
  • the aliphatic acyl may include saturated or
  • alkanoyl such as lower alkanoyl (e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, etc.)
  • alkylsulfonyl such as lower alkylsulfonyl (e.g. mesyl, ethylsulfonyl, propylsulfonyl,
  • alkenyloxycarbonyl such as lower alkenyloxycarbo ⁇ yl (e.g. vinyloxycarbonyl, allyloxycarbonyl, etc.), alkenoyl such as lower alkenoyl (e.g. acryloyl, methacryloyl, crotonoyl, etc.), cycloalkanecarbonyl such as
  • cyclo(lower)alkanecarbonyl e.g. cyclopropanecarbonyl, cyclopentanecarb ⁇ nyl, cyclohexanecarbonyl, etc.
  • cyclo(lower)alkanecarbonyl e.g. cyclopropanecarbonyl, cyclopentanecarb ⁇ nyl, cyclohexanecarbonyl, etc.
  • the aliphatic acyl substituted with aromatic group(s) may include aralkoxycarbonyl such as
  • phenyl(lower)alkoxycarbonyl e.g. benzyloxycarbonyl, phenethyloxycarbonyl, etc.
  • phenyl(lower)alkoxycarbonyl e.g. benzyloxycarbonyl, phenethyloxycarbonyl, etc.
  • acyl groups may be further substituted with one or more suitable substituent(s) such as nitro, halogen as mentioned below, and the like, and preferable acyl having such substituent(s) may be nitroaralkoxycarbonyl (e.g.
  • nitrobenzyloxycarbonyl, etc. trihalo(lower)alkyl (e.g. trifluoroacetyl, etc.), and the like.
  • trihalo(lower)alkanoyl such as triflu ⁇ ro(lower)- alkanoyl (e.g. trifluoroacetyl, etc.);
  • N-(lower)alkylcarbamoyl e.g. N-ethylcarbamoyl
  • hydroxy-protective group means a hydroxy group protected by a conventional hydroxy-protective group, and suitable "hydroxy-protective group may include lower alkyl as defined above, acyl as defined above, ar( lower)alkyl such as mono-, di- or triphenyl(lower)alkyl (e.g. trityl, etc.), preferably lower alkyl and tri ⁇ henyl(lower)alkyl, and the most preferably methyl and trityl.
  • heterocyclic-(lower)alkyl may include 3 to 12, preferably 5 or 6-membered heteromonocyclic group containing at least one hetero atom such as oxygen atom, nitrogen atom and sulfur atom (e.g. morpholino, etc.), and the like.
  • heterocyclic group means saturated or unsaturated, monocyclic or polycyclic heterocyclic group containing at least one herero-atom such as oxygen, sulfur, nitrogen atom and the like.
  • heterocyclic group may be heterocyclic group such ast
  • heterocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, etc.; wherein said heterocyclic group may be substituted by one or more, preferably one or two suitable substituent(s) such as lower alkyl as mentioned above, in which more preferable example may be saturated 5 or 6-membered
  • heteromonocyclic group containing 1 to 4 nitrogen atom(s), or containing 1 to 3 oxygen atom(s) and 1 to 3 nitrogen atora(s), optionally substituted by lower alkyl.
  • Suitable lower alkyl group in "heterocyclic- (lower)alkyl” can be referred to the ones as mentioned above.
  • alkylpiperazinylcarbonyl and morpholinylcarbonyl and the most preferable one may be 4-methylpiperazin-1-ylcarbonyl and morpholinocarbonyl.
  • alkylpiperazinyl(lower)alkyl and morpholinyl(lower)alkyl and the most preferable one may be 4-methyl ⁇ i ⁇ erazin-l- ylmethyl and morpholinomethyl.
  • Suitable "halogen” may be fluorine, chlorine, bromine, iodine, and more preferred example may be chlorine.
  • Suitable "lower alkylene” may include straight or branched one such as methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene,
  • Suitable “leaving group” may include imidazole, lower alkylimidazole (e.g. 2-methylimidazole, etc.), an acid residue such as halogen as mentioned above (e.g. chlorine, etc.), and the like.
  • Suitable "lower alkylthio” may include straight or branched one such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, t-butylthio, pentylthio,
  • Suitable "hydroxy(lower)alkyl” may include
  • Suitable "protected hydroxy(lower)alkyl” means hydroxy(lower)alkyl protected by a conventional hydroxy-protective group as mentionted in the explanation of
  • triphenyl(lower)alkoxy(lower)alkyl and the most preferable one may be methoxymethyl and trityloxymethyl.
  • the quinazoline derivative (I) or the pharmaceutically acceptable salts thereof is used in the form of a conventional pharmaceutical preparation which contains said compound, as an active ingredient, in admixture with pharmaceutically acceptable carriers such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral and external administration, particularly oral administration or topical administration to eye is preferable (e.g. eye lotion, eye drop, etc.).
  • pharmaceutically acceptable carriers such as an organic or inorganic solid or liquid excipient which is suitable for oral, parenteral and external administration, particularly oral administration or topical administration to eye is preferable (e.g. eye lotion, eye drop, etc.).
  • the pharmaceutical preparations may be in solid form such as tablets, granules, powders, capsules, dispersible granules or powders, or liquid form such as solutions, suspensions, syrups, emulsions, lemonades, and the like.
  • Formulations for oral use may also be presented as hard gelatine capsules wherein the active ingredient is mixed with an inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin, or as soft gelatine capsules wherein the active ingredient is mixed with an oil medium, for example arachis oil, liquid paraffin, or olive oil.
  • an inert solid diluent for example calcium carbonate, calcium phosphate or kaolin
  • an oil medium for example arachis oil, liquid paraffin, or olive oil.
  • Aqueous suspensions contain the active compound in admixture with excipients suitable for the manufacture of aqueous suspensions.
  • excipients are suspending agents, for example sodium carboxymethylcellulose,
  • dispersing or wetting agents may be a naturally occurring phosphatides, for example lecithin or
  • condensation products of an alkylene oxide with fatty acids for example of polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaetyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol, for example polyoxyethylene sorbitol monooleate, or condensation product of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example
  • the said aqueous suspensions may also contain one or more preservatives, for example ethyl n-propyl or p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents such as sucrose, saccharin, or sodium or calcium cyclamate.
  • preservatives for example ethyl n-propyl or p-hydroxybenzoate
  • coloring agents for example ethyl n-propyl or p-hydroxybenzoate
  • one or more flavoring agents such as sucrose, saccharin, or sodium or calcium cyclamate.
  • sweetening agents such as sucrose, saccharin, or sodium or calcium cyclamate.
  • preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives.
  • a dispersing or wetting agent e.g., sodium tartrate
  • suspending agent e.g., sodium EDTA
  • preservatives e.g., sodium EDTA, sodium EDTA, sodium tartrate, sodium tartrate, sodium tartrate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium bicarbonate, sodium sulf
  • Syrups and elixirs may be formulated with sweetening agents, for example glycerol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and favoring and coloring agents.
  • the pharmaceutical compositions may be in the form of a sterile injectable preparation, for example as a sterile injectable aqueous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above.
  • the sterile injectable preparation may also be a Bterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butane diol.
  • auxiliary substances such as lactose, stearic acid, magnesium stearate, terra alba, sucrose, corn starch, talc, gelatin, agar, pectin, peanut oil, olive oil, cacao butter, ethylene glycol, tartaric acid, citric acid, fumaric acid, and the like.
  • the dosage of the compound (I) may vary from and also depend upon the age, conditions of the patient, a kind of diseases, a kind of the compound ⁇ I) to be pplied, etc. In general, amount between about 0.001 mg and about 300 mg. preferably about 0.1 mg to about 50 mg per day may be administered to a patient. An average single dose of about 0.001 mg, 0.01 mg, 0.03 mg, 0.1 mg, 0.3 mg, 0.6 mg, 1.0 mg, 3.0 mg, 10.0 mg, 50.0 mg, 100.0 mg, of the object compound (I) of the present invention may be used.
  • Example 1 The following Examples are given for the purpose of illustrating this invention in more detail.
  • Total volume 10 ml The above-mentioned ingredients were mixed to provide 10 ml of the ophthalmic solution.
  • sulpiride 3.2 mg/kg was intravenously injected, and. then 20 minutes later the second stimulation was induced.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

On décrit une utilisation d'un composé qui correspond à la formule (I) où R1 et R2 représentent chacun hydrogène, halogène, nitro, amino, amino protégé, hydroxyamino, alkyle inférieur, hydroxy, hydroxy protégé, sulfamoyle, carboxy, carboxy protégé, mercapto, carbonyle hétérocyclique éventuellement substitué, alkyle (inférieur) hétérocyclique éventuellement substitué, alkylthio inférieur, alkyle (inférieur) hydroxy ou alkyle (inférieur) hydroxy protégé; R3 représente aryle ou éventuellement son ou ses substituants appropriés, et A représente alkylène inférieur. Ce composé, ou un de ses sels acceptables sur le plan pharmaceutique se prête au traitement de différentes affections choisies dans le groupe consistant en hypertrophie cardiaque, néphropathies, telles que néphrite ou insuffisance rénale, artériosclérose oblitérante, thrombus obstructif, embole artériel, syndrome de Bürger-Grütz, acrocyanose, engelures, gelures, troubles de l'ovulation entraînant la production de prolactine, tumeur de l'hypophyse entraînant la production de prolactine, rétention lactée puerpérale, galactorrhée puerpérale, hypertrophie distale, gigantisme d'origine hypophysaire, troubles mentaux, maladies cérébro-vasculaires, tachycardie accompagnée d'hypertension sympathique, hyperaldostéronisme, et complications dues au diabète.
PCT/JP1993/000307 1992-03-16 1993-03-15 Nouvelle utilisation d'un derive de quinazoline WO1993018769A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB929205702A GB9205702D0 (en) 1992-03-16 1992-03-16 A new use of a quinazoline derivative
GB9205702.5 1992-03-16

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WO1993018769A2 true WO1993018769A2 (fr) 1993-09-30
WO1993018769A3 WO1993018769A3 (fr) 1993-11-25

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10752640B2 (en) 2014-08-01 2020-08-25 Nuevolution A/S Compounds active towards bromodomains

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0436157A1 (fr) * 1990-01-02 1991-07-10 Fujisawa Pharmaceutical Co., Ltd. Dérivés de quinazoline et leur préparation
WO1993005035A1 (fr) * 1991-09-06 1993-03-18 Fujisawa Pharmaceutical Co., Ltd. Derives de quinazoline et leur preparation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0436157A1 (fr) * 1990-01-02 1991-07-10 Fujisawa Pharmaceutical Co., Ltd. Dérivés de quinazoline et leur préparation
WO1993005035A1 (fr) * 1991-09-06 1993-03-18 Fujisawa Pharmaceutical Co., Ltd. Derives de quinazoline et leur preparation

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CARDIOVASCULAR DRUGS AND THERAPY vol. 4, no. S1, 1990, pages 73 - 84 C. COBO ET AL. ,V. COTO ET AL. , G.P. VYSSOULIS ET AL. 'EFFECTS OF KETANSERIN ON LEFT VENTRICULAR HYPERTROPHY IN HYPERTENSIVE PATIENTS, REGRESSION OF LEFT VENTRICULAR HYPERTROPHY AND SYSTOLIC FUNCTION IN HYPERTENSIVE PATIENTS DURING LONG-TERM TREATMENT WITH KETANSERIN, LEFT VENTRICULAR HYPERTROPHY REGRESSION AND FUNCTION CHANGES WITH KETANSERIN ...' *
GENERAL PHARMACOLOGY vol. 20, no. 6, 1989, pages 755 - 758 M. MIDOL-MONNET ET AL. 'STUDY ON THE MECHANISM OF 5-HT-INDUCED TACHYCARDIA IN THE PITHED RAT' *
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY vol. 7, no. S7, 1985, pages S70 - S75 S. SAMAN ET AL. 'SEROTONIN AND THE HEART: EFFECTS OF KETANSERIN ON MYOCARDIAL FUNCTION, HEART RATE, AND ARRHYTHMIAS' *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10752640B2 (en) 2014-08-01 2020-08-25 Nuevolution A/S Compounds active towards bromodomains

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GB9205702D0 (en) 1992-04-29

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