WO2004019926A1 - Agent preventif et/ou curatif de l'insuffisance cardiaque - Google Patents

Agent preventif et/ou curatif de l'insuffisance cardiaque Download PDF

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Publication number
WO2004019926A1
WO2004019926A1 PCT/JP2003/011011 JP0311011W WO2004019926A1 WO 2004019926 A1 WO2004019926 A1 WO 2004019926A1 JP 0311011 W JP0311011 W JP 0311011W WO 2004019926 A1 WO2004019926 A1 WO 2004019926A1
Authority
WO
WIPO (PCT)
Prior art keywords
heart failure
group
therapeutic agent
preventive
hydrogen atom
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/JP2003/011011
Other languages
English (en)
Japanese (ja)
Inventor
Nobuakira Takeda
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.)
Tanabe Pharma Corp
Original Assignee
Mitsubishi Pharma Corp
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 Mitsubishi Pharma Corp filed Critical Mitsubishi Pharma Corp
Priority to JP2004532769A priority Critical patent/JPWO2004019926A1/ja
Priority to AU2003257591A priority patent/AU2003257591A1/en
Publication of WO2004019926A1 publication Critical patent/WO2004019926A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Definitions

  • the present invention relates to a prophylactic and / or therapeutic agent for heart failure.
  • the normal heart plays a role of a pump that supplies necessary and sufficient blood to various organs and tissues at rest and at the time of daily activities.However, the heart's pumping function deteriorates for various reasons, and the heart becomes indispensable to the body.
  • Clinical conditions such as abnormalities that occur when it is impossible to pump necessary and sufficient blood, such as dyspnea, sitting breathing, edema, chest and ascites accumulation, depressed liver, and oliguria Is defined as heart failure.
  • heart failure is a complex formation of various heart abnormalities, resulting in ventricular dysfunction and the above-mentioned clinical symptoms. Therefore, it is thought that various causes exist in heart failure at the same time, and it is not enough to prevent and / or treat it with a single prophylactic and / or therapeutic agent, and it has a new mechanism. This is an area where prophylactic and / or therapeutic agents are expected.
  • Ketanserin a blocking 5 HT 2 receptor antagonist
  • An object of the present invention is to provide a new method for preventing and / or treating heart failure. It is to provide a new drug.
  • a prophylactic and / or therapeutic agent for heart failure comprising an aminoalkoxybibenzyl represented by the following general formula (1), a pharmaceutically acceptable salt thereof and a solvate thereof as an active ingredient.
  • Rl represents a hydrogen atom, a halogen atom, a C1-C5 alkoxy group, or a C2-C6 dialkylamino group
  • R2 represents a hydrogen atom, a halogen atom or a C1
  • R 3 represents a hydrogen atom, a hydroxyl group
  • A represents a C3-C5 alkylene group which may be substituted with a carbonyl group.
  • m represents an integer of 0-5.
  • (2) the compound represented by the general formula (1), which is selected from a compound represented by the following formula (2), a salt thereof and a solvate thereof: For preventing and / or treating heart failure.
  • the prophylactic and / or therapeutic agent for heart failure comprises an aminoalkoxypibenzyl represented by the general formula (1), a pharmaceutically acceptable salt thereof, and a solvate thereof as an active ingredient.
  • a salt has a broad meaning including an ester.).
  • R 1 is a hydrogen atom; a halogen atom such as a chlorine atom or a fluorine atom; a methoxy group, an ethoxy group, a butoxy group, or the like.
  • R 4 is an amino group or a methylamino group, an ethylamino group, a butylamino group, a hexylamino group, a heptylamino group; Represents an amino group having 1 to 2 alkyl groups having 1 to 8 carbon atoms, such as a amino group, a dimethylamino group, a acetylamino group, a methylethylamino group, or a trimethyleneamino group; It represents a 4- to 6-membered polymethylamino group in which a ring such as a pentamethyleneamino group or a 3-hydroxypropylmethyleneamino group may be substituted by a carbonyl group.
  • 'Table 11 shows some of the compounds of the above general formula (1) which are preferably used in the present invention.
  • R 1 is preferably a hydrogen atom, an alkoxy group of 1 to C5 or a C 2 to (: 6 dialkylenoamino group, and R 2 is preferably a hydrogen atom; Is an amino or trimethylene group having at least one C1 to C8 alkyl group, or a 4 to 6-membered port having a pentamethylen group.
  • it is a dimethyleneamino group
  • m is preferably an integer from 0 to 2.
  • R 1 is a methoxy group and R 2 is A compound of No. 15 in which R 3 is a hydroxyl group, R 4 is a dimethylamino group, and R 3 is a hydroxyl group (hereinafter referred to as “M-1”) and its succinic acid It is a compound of N 0.14 which is an ester.
  • a pharmaceutically acceptable salt of the compound represented by the general formula (1) can also be used.
  • Acids that form such salts include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid conodic acid, adipic acid, propionic acid, alcohol replacement For bridal (aiij26) Phosphoric acid, maleic acid, oxalic acid, citric acid, benzoic acid, toluenesulfonic acid, methanesulfonic acid and the like are used.
  • a solvate of the compound represented by the general formula (1) or a salt thereof, for example, a hydrate can also be used.
  • Aminoalkoxybibenzyles of the general formula (1) used in the present invention are well-known compounds as described in JP-A-58-32884.
  • the present invention is applied to a patient who has already been administered a drug selected from an ACE inhibitor, a diuretic, and a dioxin preparation. It is also possible to administer the drug in combination.
  • Dixylose preparations include digitoxin (digitoxin), digoxin (digoxin, digosine), methyl digoxin (ranilapid), deslanoside (digillanogen C), and lanana. Tosid C (digylanogen C), prossilazin (talusin, caladrine) and the like. Note that the above parentheses are registered trademarks.
  • the method for preventing heart failure and administering the Z or therapeutic agent according to the present invention is optional.
  • parenteral administration such as subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, and oral administration are possible.
  • the dosage will depend on the patient's age, health, weight, type of concurrent treatment, if any, frequency of treatment, nature of the effect desired, and the like. Generally, the daily dose of the active ingredient is 0.5 to 50 mg / kg body weight. ⁇ 30 mg / kg body weight, given once or more times.
  • the compound of the present invention is administered orally in the form of tablets, capsules, powders, liquids, elixirs and the like, and in the case of parenteral administration, in the form of a liquid or sterile liquid such as a suspending agent. Used. When used in the form as described above, solid or liquid non-toxic pharmaceutical carriers can be included in the composition.
  • capsules of ordinary gelatin type are used.
  • the active ingredient is tabletted and packaged with or without adjuvants.
  • capsules, tablets and powders generally contain from 5 to 95%, preferably from 5 to 90% by weight of active ingredient.
  • these administration forms preferably contain 5 to 500 mg, preferably 25 to 25 Omg, of the active ingredient per administration.
  • liquid carrier water or an oil of animal or plant origin or synthetic such as petroleum, peanut oil, soybean oil, mineral oil, sesame oil and the like is used.
  • Injectable solutions usually contain 0.5 to 20%, preferably 1 to 10% by weight of active ingredient.
  • the blood brain-type sodium natriuretic peptide (BNP) concentration was measured at 75.6 pg / bp.
  • the patient showed high dl (normally less than 20 pg / dl), so he was judged to be in a state of congestive heart failure due to hypertension and diabetes mellitus, and started treatment for heart failure.
  • NYHA II New York Heart Association
  • Blobless Takeda Pharmaceutical Co., Ltd. for the treatment of underlying diseases 8 mg / day, Perdipine (Yamanouchi Pharmaceutical) 60 mg / day, Seloken (Astra-Zeneca) 60 mg / day, Sigmat (Chugai) 15 mg / day, Nitrodam He was taking one TTS (North Pharmaceuticals Co., Ltd.) per day, and was eating at the same time.
  • the present invention can provide a prophylactic and / or Z or therapeutic agent useful for heart failure.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un agent préventif et/ou curatif de l'insuffisance cardiaque qui contient comme principe actif l'aminoalcoxybenzyle représenté par la formule générale (I), un sel pharmaceutiquement acceptable et un solvate de celui-ci.
PCT/JP2003/011011 2002-08-30 2003-08-29 Agent preventif et/ou curatif de l'insuffisance cardiaque Ceased WO2004019926A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2004532769A JPWO2004019926A1 (ja) 2002-08-30 2003-08-29 心不全の予防及び／又は治療剤
AU2003257591A AU2003257591A1 (en) 2002-08-30 2003-08-29 Preventive and/or therapeutic agent for heart failure

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002254654 2002-08-30
JP2002-254654 2002-08-30

Publications (1)

Publication Number Publication Date
WO2004019926A1 true WO2004019926A1 (fr) 2004-03-11

Family

ID=31972848

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/011011 Ceased WO2004019926A1 (fr) 2002-08-30 2003-08-29 Agent preventif et/ou curatif de l'insuffisance cardiaque

Country Status (4)

Country Link
JP (1) JPWO2004019926A1 (fr)
AU (1) AU2003257591A1 (fr)
TW (1) TW200406199A (fr)
WO (1) WO2004019926A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02304022A (ja) * 1989-05-18 1990-12-17 Mitsubishi Kasei Corp セロトニン拮抗剤

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8827988D0 (en) * 1988-11-30 1989-01-05 Smith Kline French Lab Chemical compounds
JP2544239B2 (ja) * 1989-08-31 1996-10-16 花王株式会社 血管拡張剤
US5585361A (en) * 1994-06-07 1996-12-17 Genzyme Corporation Methods for the inhibition of platelet adherence and aggregation
WO2002009727A1 (fr) * 2000-07-28 2002-02-07 Bioenergy, Inc. Compositions et procedes ameliorant les fonctions cardio-vasculaires
ATE431830T1 (de) * 2000-12-28 2009-06-15 Kissei Pharmaceutical Glucopyranosylpyrazolderivate und deren verwendung in arzneimitteln

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02304022A (ja) * 1989-05-18 1990-12-17 Mitsubishi Kasei Corp セロトニン拮抗剤

Also Published As

Publication number Publication date
TW200406199A (en) 2004-05-01
JPWO2004019926A1 (ja) 2005-12-15
AU2003257591A1 (en) 2004-03-19

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