WO2004058745A1 - 光学活性なジヒドロピリジン誘導体 - Google Patents
光学活性なジヒドロピリジン誘導体 Download PDFInfo
- Publication number
- WO2004058745A1 WO2004058745A1 PCT/JP2003/016616 JP0316616W WO2004058745A1 WO 2004058745 A1 WO2004058745 A1 WO 2004058745A1 JP 0316616 W JP0316616 W JP 0316616W WO 2004058745 A1 WO2004058745 A1 WO 2004058745A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ester
- acid
- amino
- methyl
- dihydro
- Prior art date
Links
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
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- 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
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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 relates to an optically active dihydropyridine derivative or a pharmacologically acceptable salt thereof, which has an excellent antihypertensive effect, a cardioprotective effect, an anti-atherosclerotic effect or a renal impairment improving effect, and hypertension containing them.
- the present invention relates to a therapeutic or prophylactic agent for heart disease, arteriosclerosis or renal disorder.
- Dihydropyridine-based calcium antagonist ( ⁇ ) -2-amino-1,4-dihydroxy 6-methyl-4-, (3-nitrophenyl) -3,5-pyridinedicarboxylic acid 3- (1-diphenylmethyla Zetidine-3-yl) ester 5-isopropylester (hereinafter also referred to as compound (I)) is a calcium antagonizing, antihypertensive, vasodilator, cardioprotective, antiatherosclerotic, and diuretic effect. It has pharmacological activities such as renal impairment inhibitory action and lipid peroxide production inhibitory action, and has low toxicity, and is useful as a drug for treating cardiovascular diseases such as hypertension, angina pectoris and arteriosclerosis. (See, for example, Japanese Patent Publication No. 3-31715 (U.S. Pat. No. 4,772,996).)
- the present inventors have conducted intensive studies on the pharmacological activities of various dihydropyridine calcium antagonists for many years with the aim of developing an excellent drug for treating or preventing circulatory diseases, and as a result, the racemic
- R 2-amino-1,4, dihydro-6—methyl-14- (3-nitrophenyl) -1,3,5—pyridinedicarboxylic acid 3—
- (1 —Diphenylmethylazetidin-3-yl) ester 5-isopropyl ester is a particularly excellent calcium antagonist, antihypertensive, vasodilator, cardioprotective, antiatherosclerotic, and diuretic.
- the active ingredient contained in the preventive or therapeutic agent for circulatory system diseases such as hypertension and angina is (R) -2-amino-1,4-dihydro-6-methyl-4-1 (3) —Nittophenyl) —3,5-Pyridinedicarboxylic acid 3- (1-diphenylmethylazetidine-1-yl) ester 5-isopropyl ester.
- the 5-isopropyl ester can be salted, if desired, according to conventional methods.
- such salts can be prepared by reacting compound (I) with the corresponding acid in a solvent (eg, ethers, esters or alcohols, preferably ethers) for 5 minutes at room temperature. It can be obtained by treating for 30 minutes and collecting the precipitated crystals by filtration or distilling off the solvent under reduced pressure.
- a solvent eg, ethers, esters or alcohols, preferably ethers
- salts include hydrofluoric acid, hydrochloride, hydrobromide, hydroiodide, nitrate, perchlorate, sulfate or a mineral acid salt such as phosphoric acid: ⁇ ; methanesulfonic acid Salts, sulphonates such as trifluoromethanesulphonate, ethanesulphonate, benzenesulphonate or p-toluenesulphonate; fumarate, succinate, citrate, tartrate, oxalate Or carboxylate such as maleate; or amino acid salt such as glutamate or aspartate.
- phosphoric acid ⁇
- methanesulfonic acid Salts such as trifluoromethanesulphonate, ethanesulphonate, benzenesulphonate or p-toluenesulphonate
- fumarate, succinate, citrate, tartrate, oxalate Or carboxylate such as maleate
- amino acid salt such
- Ester 5-isopropyl ester or a pharmacologically acceptable salt thereof has particularly excellent calcium antagonism, anti-hypertension, vasodilator, cardioprotection, anti-atherosclerosis, diuresis, renal impairment, and i. It exhibits pharmacological activity such as oxidized lipid production inhibitory activity and is useful as a preventive or therapeutic agent (especially therapeutic agent) for cardiovascular diseases (especially hypertension) such as hypertension, angina or arteriosclerosis.
- excipients include, for example, milk, sucrose, glucose, mannitol or mannitol.
- Sugar derivatives such as sorbitol; corn starch, potato starch, starch derivatives such as ⁇ -starch or dextrin; cell mouth derivatives such as crystalline cellulose; gum arabic; dextran; or organic such as pullulan.
- excipients; or silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate or magnesium mesosilicate aluminium; phosphates such as calcium hydrogen phosphate; carbonic acid such as calcium carbonate Salts; and inorganic excipients such as sulfates such as calcium sulfate.
- lubricant examples include: stearic acid; metal stearate such as calcium stearate or magnesium stearate; talc; colloidal silica; waxes such as beeswax or gay; boric acid; adipic acid Sulphates such as sodium sulphate; dalicol; fumaric acid; sodium benzoate; D, L-isocyanate; lauryl sulphates such as sodium lauryl sulphate or magnesium lauryl sulphate; Silicic acids; or the above-mentioned starch derivatives.
- binder for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, or a compound similar to the above-mentioned excipient can be mentioned.
- disintegrant examples include cellulose derivatives such as low-substituted hydroxypropylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium or internally crosslinked carboxymethylcellulose sodium; crosslinked polyvinylpyrrolidone; or carboxymethyl starch. Alternatively, mention may be made of chemically modified starch / cellulose, such as carboxymethylsuccinate.
- Emulsifiers include, for example, colloidal clays such as bentonite or pea gum; metal hydroxides such as magnesium hydroxide or aluminum hydroxide; anionic salts such as sodium lauryl sulfate or calcium stearate.
- Surfactants cationic surfactants such as benzalkonium chloride; and nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester or sucrose fatty acid ester.
- the "stabilizer” used is, for example, parahydroxybenzoic acid esters such as methyl paraben or propyl paraben; alcohols such as chlorobutanol, benzyl alcohol or phenylethyl alcohol; Benzol; phenols such as phenol or cresol; thimerosal; dehydroacetic acid; or sorbic acid.
- flavoring agent examples include sweeteners such as saccharin sodium or aspartame; acidulants such as cunic acid, malic acid or tartaric acid; or menthol, lemon extract or orange extract. Flavors can be mentioned.
- diluent examples include lactose, mannitol, glucose, sucrose, calcium sulfate, calcium phosphate, hydroxypropylcellulose, microcrystalline cellulose, water, ethanol, polyethylene glycol, propylene glycol, glycerol, starch, Examples thereof include those usually used as a diluent, such as polyvinylpyrrolidone, magnesium aluminate metasilicate or a mixture thereof.
- Porcine heart microsomes were used as the source of L-type calcium channels, and 3 H-nitrendipine was used as the ligand for L-type calcium channels.
- a HEPES (50 mM, pH 7.4) buffer add microsomal (0.2 mg protein Zml), 3 H-drenendipine (0.1 nM) and test drug (racemic, R- or S-form) at room temperature for 30 minutes. After reacting for 3 minutes, 3 H-ditrandipine bound to the microsome membrane fraction was measured in a liquid scintillation counter. The count (non-specific binding amount) in the presence of 10 ⁇ of unlabeled nitrendipine was subtracted to determine the specific binding amount.
- Ki IC 50 / (l + [L] / Kd) ([L] is 3H—concentration of nitrendipine)
- the S-form 700 460 R-form was found to be about 500-fold more potent than the S-form, and more than twice as potent as the racemic form.
- a forcenula for drug administration was introduced into the hip vein, and the compound was intravenously administered under anesthesia. Blood pressure was measured.
- Racemate (20 pg / kg) and R-isomer results (10 pg / kg) were compared in Table 2, the experiment of another series, R form (3 pg / kg, 10pg / k g) and S-form (1000 pg / Table 3 shows the results of the comparison of
- the R-form shows about 2 times stronger antihypertensive activity than the racemic form and about 300 times stronger than the S-form.
- this powder After mixing the powder of the above formulation and passing through a 60 mesh sieve, this powder is placed in a 250 mg 3 ⁇ gelatin capsule to make a capsule.
- the powder of the above formulation is mixed and tableted with a tableting machine to give a tablet of 200 mg per tablet. These tablets can be sugar-coated if necessary. [Possibility of industrial use]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ540845A NZ540845A (en) | 2002-12-24 | 2003-12-24 | Optically active dihydropyridine derivative |
BR0317671-1A BR0317671A (pt) | 2002-12-24 | 2003-12-24 | Composto |
EP03786279A EP1577309A4 (en) | 2002-12-24 | 2003-12-24 | OPTICALLY ACTIVE DIHYDROPYRIDINE DERIVATIVE |
AU2003296091A AU2003296091B2 (en) | 2002-12-24 | 2003-12-24 | Optically active dihydropyridine derivative |
CA2511595A CA2511595C (en) | 2002-12-24 | 2003-12-24 | Optically active dihydropyridine derivative |
MXPA05006885A MXPA05006885A (es) | 2002-12-24 | 2003-12-24 | Derivado de dihidropiridina opticamente activo. |
IL169163A IL169163A (en) | 2002-12-24 | 2005-06-15 | Optically active dihydropyridine derivative and pharmaceutical compositions containing the same |
US11/155,844 US20050272715A1 (en) | 2002-12-24 | 2005-06-17 | Optically active dihydropyridine derivative |
NO20053581A NO331384B1 (no) | 2002-12-24 | 2005-07-22 | Optisk aktivt dihydropyridinderivat, preventivt eller terapeutisk middel som inneholder derivatet og anvendelse av derivatet for fremstilling av et medikament for forhindring eller behandling av en sykdom i sirkulasjonssystemet. |
US12/214,940 US7795281B2 (en) | 2002-12-24 | 2008-06-24 | Optically active dihydropyridine derivative |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002-371901 | 2002-12-24 | ||
JP2002371901 | 2002-12-24 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/155,844 Continuation-In-Part US20050272715A1 (en) | 2002-12-24 | 2005-06-17 | Optically active dihydropyridine derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004058745A1 true WO2004058745A1 (ja) | 2004-07-15 |
Family
ID=32677216
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2003/016616 WO2004058745A1 (ja) | 2002-12-24 | 2003-12-24 | 光学活性なジヒドロピリジン誘導体 |
Country Status (16)
Country | Link |
---|---|
US (2) | US20050272715A1 (ja) |
EP (1) | EP1577309A4 (ja) |
KR (1) | KR101008871B1 (ja) |
CN (1) | CN100549005C (ja) |
AU (1) | AU2003296091B2 (ja) |
BR (1) | BR0317671A (ja) |
CA (1) | CA2511595C (ja) |
IL (1) | IL169163A (ja) |
MX (1) | MXPA05006885A (ja) |
NO (1) | NO331384B1 (ja) |
NZ (1) | NZ540845A (ja) |
PL (1) | PL375996A1 (ja) |
RU (1) | RU2294328C2 (ja) |
TW (1) | TWI341312B (ja) |
WO (1) | WO2004058745A1 (ja) |
ZA (1) | ZA200505110B (ja) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100352818C (zh) * | 2005-09-23 | 2007-12-05 | 四川科伦药业股份有限公司 | 一种改进的制备阿折地平的方法 |
JP2008290989A (ja) * | 2007-05-28 | 2008-12-04 | Ube Ind Ltd | ジヒドロピリジン誘導体の酸付加塩を含有する医薬 |
CN102503833A (zh) * | 2011-10-12 | 2012-06-20 | 北京汉典中西药研究开发中心 | 2-(3-硝基亚苄基)乙酰乙酸异丙酯的制备方法 |
JP5181675B2 (ja) * | 2005-11-29 | 2013-04-10 | 宇部興産株式会社 | ジヒドロピリジン誘導体の酸付加塩 |
JP5181674B2 (ja) * | 2005-11-29 | 2013-04-10 | 宇部興産株式会社 | 光学活性なジヒドロピリジン誘導体の酸付加塩 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101591329B (zh) * | 2009-07-03 | 2013-12-25 | 北京华禧联合科技发展有限公司 | 一种制备手性阿折地平及其可接受盐的方法 |
DE102013020666B4 (de) * | 2013-11-29 | 2017-09-14 | Staedtler Mars Gmbh & Co. Kg | Bleimine für Schreib-, Zeichen- und/oder Malgeräte sowie Verfahren zu deren Herstellung |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0266922A1 (en) * | 1986-10-09 | 1988-05-11 | Sankyo Company Limited | Dihydropyridine derivatives, their preparation and their use |
JPH11116570A (ja) * | 1997-10-14 | 1999-04-27 | Ube Ind Ltd | ジヒドロピリジン誘導体の製造法 |
WO2001076598A1 (fr) * | 2000-04-11 | 2001-10-18 | Sankyo Company, Limited | Compositions pharmaceutiques stabilisees contenant des bloqueurs des canaux calcium |
WO2002009761A2 (en) * | 2000-07-27 | 2002-02-07 | Pharmacia Corporation | Epoxy-steroidal aldosterone antagonist and calcium channel blocker combination therapy for treatment of congestive heart failure |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0331715A (ja) | 1989-06-29 | 1991-02-12 | Hazama Gumi Ltd | 測点の変位自動計測方法及びその装置 |
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2003
- 2003-12-24 MX MXPA05006885A patent/MXPA05006885A/es active IP Right Grant
- 2003-12-24 TW TW092136657A patent/TWI341312B/zh not_active IP Right Cessation
- 2003-12-24 EP EP03786279A patent/EP1577309A4/en not_active Withdrawn
- 2003-12-24 PL PL03375996A patent/PL375996A1/xx unknown
- 2003-12-24 KR KR1020057011692A patent/KR101008871B1/ko not_active IP Right Cessation
- 2003-12-24 WO PCT/JP2003/016616 patent/WO2004058745A1/ja active IP Right Grant
- 2003-12-24 AU AU2003296091A patent/AU2003296091B2/en not_active Ceased
- 2003-12-24 RU RU2005119970/04A patent/RU2294328C2/ru not_active IP Right Cessation
- 2003-12-24 NZ NZ540845A patent/NZ540845A/en not_active IP Right Cessation
- 2003-12-24 CN CNB2003801098914A patent/CN100549005C/zh not_active Expired - Fee Related
- 2003-12-24 CA CA2511595A patent/CA2511595C/en not_active Expired - Fee Related
- 2003-12-24 BR BR0317671-1A patent/BR0317671A/pt not_active IP Right Cessation
-
2005
- 2005-06-15 IL IL169163A patent/IL169163A/en not_active IP Right Cessation
- 2005-06-17 US US11/155,844 patent/US20050272715A1/en not_active Abandoned
- 2005-07-22 NO NO20053581A patent/NO331384B1/no not_active IP Right Cessation
-
2006
- 2006-01-06 ZA ZA200505110A patent/ZA200505110B/en unknown
-
2008
- 2008-06-24 US US12/214,940 patent/US7795281B2/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0266922A1 (en) * | 1986-10-09 | 1988-05-11 | Sankyo Company Limited | Dihydropyridine derivatives, their preparation and their use |
JPH11116570A (ja) * | 1997-10-14 | 1999-04-27 | Ube Ind Ltd | ジヒドロピリジン誘導体の製造法 |
WO2001076598A1 (fr) * | 2000-04-11 | 2001-10-18 | Sankyo Company, Limited | Compositions pharmaceutiques stabilisees contenant des bloqueurs des canaux calcium |
WO2002009761A2 (en) * | 2000-07-27 | 2002-02-07 | Pharmacia Corporation | Epoxy-steroidal aldosterone antagonist and calcium channel blocker combination therapy for treatment of congestive heart failure |
Non-Patent Citations (9)
Title |
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ARITA MIKIO: "A new Ca-antagonist, azelnidipine, reduced blood pressure during exercise without augmentation of sympathetic nervous system in essential hypertension : a randomized, double-blind, placebo-controlled trial", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 33, no. 2, 1999, pages 186 - 192, XP002903719 * |
MIYAMOTO MASAAKI: "Shinki dihydropyridine-kei calcium kikkoyaku azelnidipine no ippan yakuri sayo", BASIC PHARMACOLOGY & THERAPEUTICS, vol. 25, 1997, pages 163 - 181 (S-1127-S-1145), XP002903714 * |
OIZUMI KIYOSHI: "Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker", JAPANESE JOURNAL OF PHARMACOLOGY, vol. 51, no. 1, 1989, pages 57 - 64, XP002903720 * |
OIZUMI KIYOSHI: "Antihypertensive effects of CS-905, a novel dihydropyridine calcium blocker, in conscious hypertensive dogs", JAPANESE JOURNAL OF PHARMACOLOGY, vol. 53, no. 2, 1990, pages 264 - 266, XP002903721 * |
SADA TASHIDO: "Cholesterol fuka usagi ni okeru koshi yosei jizokugata ca kikkozai azelnidipine no kodomyaku koka sayo", BASIC PHARMACOLOGY & THERAPEUTICS, vol. 30, no. 9, 20 September 2002 (2002-09-20), pages 721 - 728, XP002903715 * |
SADA TOSHIO: "Kekkan shinwasei o yusuru jizokugata ca kikkozai azelnidipine no yakuri tokusei (sono 2)", BASIC PHARMACOLOGY & THERAPEUTICS, vol. 30, no. 9, 20 September 2002 (2002-09-20), pages 711 - 720, XP002903717 * |
SADA TOSHIO: "Kekkan shinwasei o yususu jizokugata ca kikkizai azelnidipine no yakuri tokusei (sono 1)", BASIC PHARMACOLOGY & THERAPEUTICS, vol. 30, no. 9, 20 September 2002 (2002-09-20), pages 703 - 709, XP002903716 * |
SATOH KUMI: "Effects of azelnidipine, a dihydropyridine calcium antagonist, on myocardial stunning in dogs", JAPANESE JOURNAL OF PHARMACOLOGY, vol. 76, 1998, pages 369 - 376, XP002903718 * |
See also references of EP1577309A4 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100352818C (zh) * | 2005-09-23 | 2007-12-05 | 四川科伦药业股份有限公司 | 一种改进的制备阿折地平的方法 |
JP5181675B2 (ja) * | 2005-11-29 | 2013-04-10 | 宇部興産株式会社 | ジヒドロピリジン誘導体の酸付加塩 |
JP5181674B2 (ja) * | 2005-11-29 | 2013-04-10 | 宇部興産株式会社 | 光学活性なジヒドロピリジン誘導体の酸付加塩 |
JP2008290989A (ja) * | 2007-05-28 | 2008-12-04 | Ube Ind Ltd | ジヒドロピリジン誘導体の酸付加塩を含有する医薬 |
CN102503833A (zh) * | 2011-10-12 | 2012-06-20 | 北京汉典中西药研究开发中心 | 2-(3-硝基亚苄基)乙酰乙酸异丙酯的制备方法 |
CN102503833B (zh) * | 2011-10-12 | 2013-11-27 | 北京汉典中西药研究开发中心 | 2-(3-硝基亚苄基)乙酰乙酸异丙酯的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
NZ540845A (en) | 2008-02-29 |
KR20050088203A (ko) | 2005-09-02 |
IL169163A0 (en) | 2007-07-04 |
NO20053581L (no) | 2005-07-22 |
RU2005119970A (ru) | 2006-01-20 |
CA2511595A1 (en) | 2004-07-15 |
TW200424192A (en) | 2004-11-16 |
BR0317671A (pt) | 2005-11-29 |
EP1577309A1 (en) | 2005-09-21 |
ZA200505110B (en) | 2006-03-29 |
AU2003296091B2 (en) | 2007-07-19 |
AU2003296091A1 (en) | 2004-07-22 |
IL169163A (en) | 2012-01-31 |
RU2294328C2 (ru) | 2007-02-27 |
PL375996A1 (en) | 2005-12-12 |
US20080287411A1 (en) | 2008-11-20 |
EP1577309A4 (en) | 2007-01-24 |
US7795281B2 (en) | 2010-09-14 |
TWI341312B (en) | 2011-05-01 |
US20050272715A1 (en) | 2005-12-08 |
MXPA05006885A (es) | 2005-08-16 |
AU2003296091A8 (en) | 2004-07-22 |
CN1753885A (zh) | 2006-03-29 |
CA2511595C (en) | 2012-04-17 |
NO331384B1 (no) | 2011-12-12 |
KR101008871B1 (ko) | 2011-01-17 |
CN100549005C (zh) | 2009-10-14 |
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