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WO2006115245A1 - Dérivé de 4-éthynylisoquinoléine et préparation pharmaceutique comprenant celui-ci - Google Patents

Dérivé de 4-éthynylisoquinoléine et préparation pharmaceutique comprenant celui-ci Download PDF

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Publication number
WO2006115245A1
WO2006115245A1 PCT/JP2006/308567 JP2006308567W WO2006115245A1 WO 2006115245 A1 WO2006115245 A1 WO 2006115245A1 JP 2006308567 W JP2006308567 W JP 2006308567W WO 2006115245 A1 WO2006115245 A1 WO 2006115245A1
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WO
WIPO (PCT)
Prior art keywords
compound
solvate
hypertension
acid addition
addition salt
Prior art date
Application number
PCT/JP2006/308567
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English (en)
Japanese (ja)
Inventor
Hiroyoshi Hidaka
Masahiro Tamura
Hiroshi Nakao
Hiromichi Sigyo
Hajime Yamada
Takatoshi Ozawa
Hideo Yoshizaki
Original Assignee
D. Western Therapeutics Institute, Inc.
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 D. Western Therapeutics Institute, Inc. filed Critical D. Western Therapeutics Institute, Inc.
Publication of WO2006115245A1 publication Critical patent/WO2006115245A1/fr

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Classifications

    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • 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
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention has a potent Rho kinase inhibitory action, such as hypertension, pulmonary hypertension, cerebral vasospasm, angina pectoris, heart failure, arteriosclerosis, glaucoma, dysuria, asthma, and erectile dysfunction.
  • the present invention relates to a compound useful as a therapeutic agent for a disease and a medicine containing the same.
  • Rho one of the low molecular weight GTP-binding proteins, exists in cells as active Rho-GTP or inactive Rho-GDP, and is activated by signals from various cell membrane receptors. It is converted into an inactive Rho-GDP active Rho-GTP by the selected Rho kinase. It has been clarified that the active Rho-GTP functions as a molecular switch for various cell phenomena such as smooth muscle contraction, cell motility, cell adhesion, cell shape change, and cell proliferation via the actomyosin system. ing. Therefore, it is thought that inhibition of Rho kinase can suppress the response of various cellular phenomena existing downstream of the Rho-mediated signal transduction pathway and can be useful for treatment of diseases involving Rho.
  • Non-Patent Documents 2 and 3 recent studies have shown that not only blood pressure lowering action by inhibiting Rho kinase (see, for example, Non-Patent Documents 2 and 3) but also effective cases for pulmonary hypertension (for example, Non-Patent Documents 4-6).
  • Non-Patent Documents 7 and 8 angina Effective for glaucoma (for example, see non-patent documents 9 to 11), effective for glaucoma (for example, refer to non-patent documents 12 to 14), effective for dysuria (for example, refer to non-patent document 15), Cases that are effective as therapeutic agents for asthma (for example, see Non-Patent Documents 16 to 19) and cases that are effective for erectile dysfunction (for example, see Non-Patent Documents 20 and 21) have been reported.
  • Fasudil hydrochloride a Rho kinase inhibitor (trade name: Eryll Injection)
  • Eryll Injection a Rho kinase inhibitor
  • IC Rho kinase inhibitor
  • Patent Document 1 discloses that a Rho kinase inhibitor is useful as a prophylactic or therapeutic agent for asthma, etc., but the compound disclosed here has a 50% inhibitory concentration (IC; ⁇ ; ⁇ ) is the strongest (for example,
  • (S)-(+) —Hexahydro-1 2-methyl 1- (4-methyl 5-isoquinoline sulfol) —1H—1, 4 diazepine hydrochloride) is on the order of 1 to 100, which inhibits Rho kinase I was not satisfied with the product.
  • Rho kinase inhibitor that can reduce the dose when actually administering a Rho kinase inhibitor as a therapeutic agent, and reduce the risk of side effects caused by the reduced dose. It was.
  • Patent Document 1 Japanese Patent Laid-Open No. 11-349482
  • Non-patent literature l Nature 389 (1997): 990
  • Non-Patent Document 2 J. Cereb. Blood Flow 21 (2001): 876
  • Non Patent Literature 3 Hypertension 38 (2001): 1307
  • Non-Patent Document 4 Atheroscierosis Supplements 4 (2003): 170
  • Non-Patent Document 5 Ir. J. Med. Sci. 172 (2003): 20
  • Non-Patent Document 6 Circ. Res. 94 (2004): 385
  • Non-Patent Document 7 Br. J. Pharmacol. 130 (2000): 219
  • Non-Patent Document 8 Stroke 32 (2001): 2913
  • Non-Patent Document 9 Jpn. J. Pharmacol. 87 (2001): 34
  • Non-Patent Document 10 Br. J. Pharmacol. 134 (2001): 1724
  • Non-Patent Document 11 Circulation 105 (2002): 1545
  • Non-Patent Document 12 Invest. Ophthalmol. Visual Sci. 42 (2001): 137
  • Non-Patent Document 13 Arch. Ophthalmol. 119 (2001)
  • Non-Patent Document 14 1171, Invest. Ophthalmol. Visual Sci. 42 (2001): 1029
  • Non-Patent Document 15 Br. J. Pharmacol. 143 (2004): 431
  • Non-Patent Document 16 Jpn. J. Allergol. 48 (1999): 1079
  • Non-Patent Document 17 Eur. J. Pharmacol. 389 (2000): 103
  • Non-Patent Document 18 Eur. J. Pharmacol. 406 (2000): 273
  • Non-Patent Document 19 Br. J. Pharmacol. 132 (2001): 111
  • Non-Patent Document 20 Int. J. Impot. Res. 13 (2001): 67
  • Non-Patent Document 21 Br. J. Pharmacol. 133 (2001): 455
  • An object of the present invention is to provide a compound having potent Rho kinase inhibitory activity and a medicine containing the same.
  • a compound represented by the following formula (1) has a potent Rho kinase inhibitory activity, and has high blood pressure, pulmonary hypertension, It was found useful as a therapeutic agent for diseases such as cerebral vasospasm, angina pectoris, heart failure, arteriosclerosis, glaucoma, dysuria, asthma, and erectile dysfunction, and the present invention was completed.
  • the present invention relates to the general formula (1)
  • the present invention provides a compound represented by the above general formula (1), an acid addition salt thereof or a compound thereof.
  • the present invention provides a medicine containing a solvate as an active ingredient.
  • the present invention also provides a therapeutic agent for diseases caused by the activation of Rho kinase, comprising as an active ingredient a compound represented by the above general formula (1), an acid addition salt thereof, or a solvate thereof.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound represented by the above general formula (1), an acid addition salt thereof or a solvate thereof, and a pharmaceutically acceptable carrier.
  • the present invention provides use of a compound represented by the above general formula (1), an acid addition salt thereof or a solvent thereof for producing a pharmaceutical.
  • the present invention provides a method for treating a disease caused by the activity of Rho kinase administered with a compound represented by the above general formula (1), an acid addition salt thereof, or a solvate thereof. is there.
  • the compound (1) of the present invention and acid addition salts thereof or solvates thereof have a strong Rho kinase inhibitory activity, and include hypertension, pulmonary hypertension, cerebral vasospasm, angina pectoris, heart failure It is useful as a therapeutic agent for diseases such as arteriosclerosis, glaucoma, dysuria, asthma, and erectile dysfunction.
  • the acid addition salt of the compound (1) of the present invention is not particularly limited as long as it is a pharmaceutically acceptable salt.
  • hydrochloride, hydrobromide, hydroiodide, sulfate Acid addition salts of mineral acids such as phosphates; benzoates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, oxalates, maleates, fumaric acids
  • Mention may be made of acid addition salts of organic acids such as salts, tartrate, citrate, acetate.
  • the compound (1) of the present invention may exist in the form of a solvate represented by a hydrate, and the solvate is also encompassed in the present invention.
  • the compound (1) of the present invention can be produced, for example, according to the following method.
  • the compound (2) which is a starting material for the compound of the present invention is generally available from Watanabe Chemical Co., Ltd.
  • the reaction for obtaining the compound (3) from the compound (2) is carried out by converting the hydroxy group of the compound (2) into methanesulfonyloxy, tosyloxy, etc. by a known method, followed by 3-amino-1-hydroxy V-ol. By reacting in a suitable solvent.
  • the methanesulfoxyloxy or tosyloxy reaction is carried out by reacting compound (2) with methanesulfonyl chloride or the like in the presence of a tertiary amine such as triethylamine.
  • a tertiary amine such as triethylamine.
  • the reaction solvent for the subsequent reaction with 3-amino-1-propanol include halogenated hydrocarbons such as dichloromethane and chloroform, and ethers such as tetrahydrofuran (THF) and jetyl ether. N, N-dimethylformamide (DMF), acetonitrile and the like.
  • the reaction is carried out by reacting at 0 ° C to around the boiling point of the solvent for 1 hour to 48 hours, preferably at 40 ° C to 100 ° C for 2 to 12 hours.
  • the proportion of 3-amino-1-propanol used is 1 to: L0 equivalent, preferably 4 to 6 equivalent to the compound (2)!
  • the amine of the obtained compound (3) is protected with a protecting group such as a tert-butoxycarbol group, a formyl group, or a benzoyl group to obtain a compound (4).
  • a protecting group such as a tert-butoxycarbol group, a formyl group, or a benzoyl group.
  • the alkoxycarbonyl group is eliminated by hydrogenation in the presence of a metal catalyst such as palladium, and the compound (5 )
  • a tert-butoxycarbonyl group is preferred.
  • the protection reaction of the amino group is carried out by reacting the compound (3) with a tert butoxycarbonyl group or the like in the presence of a tertiary amine such as triethylamine.
  • the protecting group may be removed by adding hydrogen in an alcohol solvent in the presence of noradium carbon.
  • the reaction between the primary amine (5) and the compound (6) is carried out in a suitable solvent, preferably in the presence of a necessary amount of a base.
  • a suitable solvent preferably in the presence of a necessary amount of a base.
  • the base include inorganic bases such as potassium carbonate, sodium carbonate and cesium carbonate; organic bases such as triethylamine, diisopropylethylamine and triethylenediamine.
  • the reaction solvent is the same as in the reaction for obtaining the compound (3).
  • the reaction is carried out by reacting at 0 ° C to 80 ° C for 0.5 to 24 hours, preferably at 10 ° C to 50 ° C for 1 to 8 hours.
  • Compound (6) can be synthesized by the method described in JP-A-2-67274 or a similar method.
  • Ring closure of the obtained compound (7) is carried out by Mitsunobu reaction using, for example, triphenylphosphine and azodicarboxylic acid ester to obtain compound (8).
  • compound (8) is heated to 80 ° C. in a pressure-resistant tube together with terminal acetylene such as trimethylsilylacetylene, Pd (0) catalyst, copper iodide and ammine.
  • terminal acetylene such as trimethylsilylacetylene, Pd (0) catalyst, copper iodide and ammine.
  • the compound (9) is obtained by converting it into an acetylene derivative by a known Sonogashira reaction under the conditions such as, and decomposing it with a base such as sodium hydroxide.
  • the deprotection reaction of the compound (9) is carried out by a known method according to the protecting group, for example, acid treatment, alkaline treatment or catalytic reduction.
  • the compound (1) of the present invention can be obtained by treatment with an ethyl acetate solution of hydrochloric acid or hydrogen.
  • the compound (1) of the present invention can be obtained by the above-described method, and can be further purified by a usual purification means such as a recrystallization method or column chromatography, if necessary. Ma
  • the desired salt or solvate described above can also be obtained by a conventional method.
  • the compound (1) of the present invention obtained by force, its acid addition salt or solvate thereof has a potent inhibitory activity against Rho kinase as shown in Test Example 1 described later, It is useful as a medicine for the treatment of diseases such as hypertension, cerebral vasospasm, angina pectoris, heart failure, arteriosclerosis, glaucoma, dysuria, asthma, and erectile dysfunction.
  • diseases such as hypertension, cerebral vasospasm, angina pectoris, heart failure, arteriosclerosis, glaucoma, dysuria, asthma, and erectile dysfunction.
  • the medicament of the present invention comprises the compound (1) of the present invention, a salt thereof or a solvate thereof as an active ingredient, and the dosage form is not particularly limited and can be appropriately selected according to the therapeutic purpose.
  • oral compositions, injections, suppositories, ointments, inhalants, eye drops, nasal drops, and patches can be used, and compositions suitable for these dosage forms are pharmaceutically acceptable.
  • an excipient When preparing an oral solid preparation, an excipient, and if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a corrigent, a corrigent and the like are added to the compound (1) of the present invention. Thereafter, tablets, coated tablets, granules, powders, capsules and the like can be produced by conventional methods.
  • additives include those commonly used in the art, such as lactose, sucrose, sodium chloride salt, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid, etc.
  • Excipients water, ethanol, propanol, simple syrup, dextrose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropinorestarch, methinorescenellose, ethylcellulose, shellac, canoleum phosphate, Binders such as polybulur pyrrolidone; disintegrating agents such as dried starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, lactose; purified talc, stearate, borax, polyethylene Guri Lubricants such Lumpur; sucrose, orange peel, Kuen acid, taste-masking agents or tartaric acid.
  • Binders such as polybulur pyrrolidone
  • disintegrating agents such as dried starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic acid
  • a liquid preparation, syrup, elixir, etc. are produced by a conventional method by adding a corrigent, buffer, stabilizer, flavor, etc. to the compound (1) of the present invention. can do.
  • the corrigent include those listed above, such as a buffer such as sodium citrate; and stabilizers such as tragacanth, gum arabic, and gelatin.
  • a pH adjuster, buffer, stabilizer, tonicity agent, local anesthetic, etc. are added to the compound (1) of the present invention, and subcutaneous, muscle and vein are added by a conventional method.
  • Manufacturing internal injection Can examples of the pH adjusting agent and buffering agent in this case include sodium citrate, sodium acetate, sodium phosphate and the like.
  • examples of the stabilizer include sodium pyrosulfite, EDTA, thioglycolic acid, and thiolactic acid.
  • local anesthetics include pro-caine hydrochloride and lidocaine hydrochloride.
  • isotonic agents include sodium chloride salt, glucose and the like.
  • a compound carrier known in the art such as polyethylene glycol, lanolin, cocoa butter, fatty acid triglyceride and the like is added to the compound (1) of the present invention as necessary.
  • a surfactant such as a trademark, it can be produced by a conventional method.
  • bases, stabilizers, moisturizers, preservatives and the like that are usually used in the compound (1) of the present invention are blended as necessary, and mixed and formulated by a conventional method. Is done.
  • the base include liquid paraffin, white petrolatum, honey beeswax, otatildodecyl alcohol, and raffine.
  • preservatives include methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, and propyl P-hydroxybenzoate.
  • inhalants In addition to the above, inhalants, eye drops, and nasal drops can be prepared by conventional methods.
  • the dose of the pharmaceutical agent of the present invention varies depending on age, body weight, symptoms, dosage form, number of administrations, etc., but is usually 1 to 1 day as a compound (1) of the present invention for adults. It is preferable to administer orally or parenterally in several divided doses.
  • Test Example 1 Measurement of kinase inhibitory activity
  • Rho kinase assay was performed, and a 50% inhibitory concentration value (hereinafter referred to as “IC value”) for Rho kinase was calculated.
  • Rho kinase of the compound (1) hydrochloride of the example are shown below as control compounds.
  • Example 1 Compound of Example 1 30 mg Microcrystalline cellulose 30 mg Lactose 57 mg Magnesium stearate 3 mg Total amount 120 mg The above ingredients were mixed by a conventional method and then filled into gelatin capsules to obtain capsules.
  • Formulation Example 2 (tablet) Compound of Example 1 3 Omg Starch 44 mg Starch (for paste) 5.6 mg Magnesium stearate 0.4 mg Carpoxymethylcellulose calcium 2 Omg Total amount 10 Omg The above ingredients were mixed by a conventional method to obtain tablets.
  • Example 1 Dissolve the compound of Example 1 (lOOmg) and sodium chloride salt (900mg) in about 80mL of distilled water for injection, and then add distilled water for injection to the resulting solution to a total volume of lOOmL. This was aseptically filtered and then dispensed into 10 ampoules and sealed to obtain a sterile injection.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pulmonology (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Il est exposé un composé qui a un puissant effet inhibiteur sur la Rho-kinase et qui est utile comme agent thérapeutique pour des maladies dont l'hypertension, l'hypertension pulmonaire, le vasospasme cérébral, l'angine de poitrine, l'insuffisance cardiaque, l'artériosclérose, le glaucome, la dysurie, l'asthme et un trouble de l'érection. L'invention concerne un dérivé de 4-éthynylisoquinoléine représenté par la formule générale (1), un sel obtenu par ajout d'acide de celui-ci ou un solvate du dérivé ou du sel.
PCT/JP2006/308567 2005-04-25 2006-04-24 Dérivé de 4-éthynylisoquinoléine et préparation pharmaceutique comprenant celui-ci WO2006115245A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005127007 2005-04-25
JP2005-127007 2005-04-25

Publications (1)

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WO2006115245A1 true WO2006115245A1 (fr) 2006-11-02

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7618984B2 (en) 2005-08-30 2009-11-17 Asahi Kasei Pharma Corporation Sulfonamide compound
US7964613B2 (en) 2007-02-28 2011-06-21 Asahi Kasei Pharma Corporation Sulfonamide compound
US8232292B2 (en) 2007-07-02 2012-07-31 Asahi Kasei Pharma Corporation Sulfonamide compound and crystal thereof
US8415372B2 (en) 2007-02-27 2013-04-09 Asahi Kasei Pharma Corporation Sulfonamide compound

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10310576A (ja) * 1997-03-10 1998-11-24 Hiroyoshi Hidaka イソキノリンスルフォンアミド誘導体及びこれを有効成分とする医薬
EP0885888A1 (fr) * 1996-02-02 1998-12-23 Nippon Shinyaku Company, Limited Derives de l'isoquinoline et medicaments associes
WO1999020620A1 (fr) * 1997-10-22 1999-04-29 Nippon Shinyaku Co Ltd Derive d'isoquinoleine et medicament
JP2004155661A (ja) * 2002-11-01 2004-06-03 Asahi Kasei Pharma Kk 突然死予防剤
US20050020623A1 (en) * 2002-07-22 2005-01-27 Rintaro Yamada 5-Substituted isoquinoline derivatives

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0885888A1 (fr) * 1996-02-02 1998-12-23 Nippon Shinyaku Company, Limited Derives de l'isoquinoline et medicaments associes
JPH10310576A (ja) * 1997-03-10 1998-11-24 Hiroyoshi Hidaka イソキノリンスルフォンアミド誘導体及びこれを有効成分とする医薬
WO1999020620A1 (fr) * 1997-10-22 1999-04-29 Nippon Shinyaku Co Ltd Derive d'isoquinoleine et medicament
US20050020623A1 (en) * 2002-07-22 2005-01-27 Rintaro Yamada 5-Substituted isoquinoline derivatives
JP2004155661A (ja) * 2002-11-01 2004-06-03 Asahi Kasei Pharma Kk 突然死予防剤

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7618984B2 (en) 2005-08-30 2009-11-17 Asahi Kasei Pharma Corporation Sulfonamide compound
US8415372B2 (en) 2007-02-27 2013-04-09 Asahi Kasei Pharma Corporation Sulfonamide compound
US7964613B2 (en) 2007-02-28 2011-06-21 Asahi Kasei Pharma Corporation Sulfonamide compound
US8232292B2 (en) 2007-07-02 2012-07-31 Asahi Kasei Pharma Corporation Sulfonamide compound and crystal thereof
US8664243B2 (en) 2007-07-02 2014-03-04 Asahi Kasei Pharma Corporation Sulfonamide compound and crystal thereof

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