WO1995005823A1 - Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsäureestern als arzneimittel - Google Patents
Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsäureestern als arzneimittel Download PDFInfo
- Publication number
- WO1995005823A1 WO1995005823A1 PCT/EP1994/002723 EP9402723W WO9505823A1 WO 1995005823 A1 WO1995005823 A1 WO 1995005823A1 EP 9402723 W EP9402723 W EP 9402723W WO 9505823 A1 WO9505823 A1 WO 9505823A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- general formula
- carbon atoms
- compounds
- medicaments
- alkylated
- Prior art date
Links
Classifications
-
- 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
-
- 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
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
Definitions
- the present invention relates to the use of partially known N-alkylated 1,4-dihydropyridinedicarboxylic acid esters as antiatherosclerotic medicaments, in particular their use for restenosis prophylaxis after angioplasty and vascular surgical measures.
- N-alkylieite 1,4-dihydropyridinedicarboxylic acid esters of the general formula (I) N-alkylieite 1,4-dihydropyridinedicarboxylic acid esters of the general formula (I)
- R 1 represents hydrogen, nitro, cyano, trifluoromethyl, trifluoromethoxy, halogen or methyl
- R 2 represents hydrogen, halogen, nitro, hydroxy, trifluoromethyl or methyl
- R 3 represents hydrogen or cyano
- R 2 and R 3 together form a condensed benzo ring
- R 4 and R 5 are the same or different and represent straight-chain or branched alkyl having up to 8 carbon atoms, which is optionally substituted by alkoxy having up to 4 carbon atoms,
- R 6 represents straight-chain or branched alkyl having up to 6 carbon atoms or cycloalkyl having 3 to 7 carbon atoms
- 1,2-Trimethyl-4- (4-trifluoromethylphenyl) -1, 4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester and 4- (4-chloro-3-trifluoromethylphenyl) -1-cyclopropyl-2 are particularly preferred , 6-dimethyl-1, 4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester in the control of atherosclerosis, in particular for restenosis prophylaxis after angioplasty and vascular surgery.
- the compounds according to the invention thus show an unforeseeable, valuable pharmacological spectrum of action.
- the compounds according to the invention inhibit smooth muscle cell proliferation.
- Vascular wall injuries lead to neointimal cell growth and consequently to a narrowing of the free vascular lumen. This process is the main cause of restenosis problems after vascular opening measures, such as percutaneous angioplasties, endarterectomies or bypass operations.
- the compounds according to the invention can therefore be used in medicines for the treatment and prophylaxis of residual enosis, e.g. after angioplasty and vascular surgery.
- the compounds according to the invention can also be used for the treatment of atherosclerosis.
- a balloon catheter is introduced into the carotid artery, this is inflated and the inside of the blood vessel is injured by moving the catheter [Clowes A.W., et al., Lab. Invest. Vol. 49, No. 3, p. 327, 1983].
- This damage causes neointimal smooth muscle proliferation, which cause stenoses.
- the extent of the vasoconstriction in the animals is determined after approximately 2 weeks by histological processing of the blood vessels by measuring the area of the proliferation tissue on vascular cross sections.
- the compounds according to the invention surprisingly significantly inhibit the vascular constrictions, as can be seen from the table below.
- the new active ingredients can be converted in a known manner into the customary formulations, such as tablets, dragées, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert, non-toxic, pharmaceutically suitable excipients or solvents.
- the therapeutically active compound should in each case be present in a concentration of about 0.5 to 90% by weight of the total mixture, ie in amounts which are sufficient to achieve the dosage range indicated.
- the formulations are prepared, for example, by stretching the active ingredients with solvents and / or carriers, optionally using emulsifiers and / or dispersants, e.g. if water is used as the diluent, organic solvents can optionally be used as auxiliary solvents.
- the application is carried out in the usual way, preferably orally or parenterally, in particular perlingually or intravenously.
- solutions of the active ingredient can be used using suitable liquid carrier materials.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP94926199A EP0714301A1 (de) | 1993-08-27 | 1994-08-16 | Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsäureestern als arzneimittel |
JP7507325A JPH09501923A (ja) | 1993-08-27 | 1994-08-16 | 薬剤としてのn−アルキル化された1,4−ジヒドロピリジンジカルボン酸エステル類の使用 |
AU76135/94A AU7613594A (en) | 1993-08-27 | 1994-08-16 | Use of n-alkylated 1,4-dihydropyridine dicarboxylic acid esters as medicaments |
KR1019960700944A KR960703594A (ko) | 1993-08-27 | 1994-08-16 | 약제로서의 N-알킬화 1,4-디히드로피리딘디카르복실산 에스테르의 용도(Use Of N-Alkylated 1,4-Dihydropyridine Dicarboxylic Acid Esters as Medicaments) |
PL94313116A PL313116A1 (en) | 1993-08-27 | 1994-08-16 | Application of n-alkalated 1,4-dihydropridinocarboxylic esters as drugs |
BG100367A BG100367A (en) | 1993-08-27 | 1996-02-19 | The use of esters of n-alkylated, 1,4-dihydropyrimidinedicarboxylic acids as medicamentous forms |
NO960777A NO960777L (no) | 1993-08-27 | 1996-02-26 | Anvendelse av N-alkylerte 1,4-dihydropyridin dikarboksylsyreestere som medikamenter |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4328884A DE4328884A1 (de) | 1993-08-27 | 1993-08-27 | Verwendung von N-alkylierten 1,4-Dihydropyridincarbonsäureestern als Arzneimittel |
DEP4328884.7 | 1993-08-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995005823A1 true WO1995005823A1 (de) | 1995-03-02 |
Family
ID=6496196
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1994/002723 WO1995005823A1 (de) | 1993-08-27 | 1994-08-16 | Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsäureestern als arzneimittel |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0714301A1 (no) |
JP (1) | JPH09501923A (no) |
KR (1) | KR960703594A (no) |
CN (1) | CN1129906A (no) |
AU (1) | AU7613594A (no) |
BG (1) | BG100367A (no) |
CA (1) | CA2170285A1 (no) |
CZ (1) | CZ43896A3 (no) |
DE (1) | DE4328884A1 (no) |
HU (1) | HUT75302A (no) |
NO (1) | NO960777L (no) |
PL (1) | PL313116A1 (no) |
WO (1) | WO1995005823A1 (no) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19741694A1 (de) * | 1997-09-18 | 1999-04-15 | Schering Ag | Verwendung Bis-Amin-Oxim-Derivaten und N¶2¶S¶2¶-Komplexderivaten zur Restenoseprophylaxe |
WO2003053930A1 (en) * | 2001-12-20 | 2003-07-03 | Bayer Healthcare Ag | 1,4-dihydro-1,4-diphenylpyridine derivatives |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10258498B2 (en) * | 2011-11-24 | 2019-04-16 | Richter Gedeon Nyrt. | 1,4-dihydropyridine derivatives with Hsp modulating activity |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3222367A1 (de) * | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Verwendung von 1,4-dihydropyridinen in antiarteriosklerotika und deren herstellung |
EP0169009A2 (en) * | 1984-07-17 | 1986-01-22 | FISONS plc | Novel dihydropyridine derivatives and their production, formulation and use as pharmaceuticals |
EP0451654A2 (de) * | 1990-04-11 | 1991-10-16 | Bayer Ag | Verwendung von N-alkylierten 1,4-Dihydropyridindicarbonsäureestern als Arzneimittel, neue Verbindungen und Verfahren zu Ihrer Herstellung |
-
1993
- 1993-08-27 DE DE4328884A patent/DE4328884A1/de not_active Withdrawn
-
1994
- 1994-08-16 CA CA002170285A patent/CA2170285A1/en not_active Abandoned
- 1994-08-16 WO PCT/EP1994/002723 patent/WO1995005823A1/de not_active Application Discontinuation
- 1994-08-16 KR KR1019960700944A patent/KR960703594A/ko not_active Application Discontinuation
- 1994-08-16 AU AU76135/94A patent/AU7613594A/en not_active Abandoned
- 1994-08-16 CN CN94193170A patent/CN1129906A/zh active Pending
- 1994-08-16 CZ CZ96438A patent/CZ43896A3/cs unknown
- 1994-08-16 EP EP94926199A patent/EP0714301A1/de not_active Withdrawn
- 1994-08-16 PL PL94313116A patent/PL313116A1/xx unknown
- 1994-08-16 JP JP7507325A patent/JPH09501923A/ja not_active Ceased
- 1994-08-16 HU HU9600472A patent/HUT75302A/hu unknown
-
1996
- 1996-02-19 BG BG100367A patent/BG100367A/xx unknown
- 1996-02-26 NO NO960777A patent/NO960777L/no unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3222367A1 (de) * | 1982-06-15 | 1983-12-15 | Bayer Ag, 5090 Leverkusen | Verwendung von 1,4-dihydropyridinen in antiarteriosklerotika und deren herstellung |
EP0169009A2 (en) * | 1984-07-17 | 1986-01-22 | FISONS plc | Novel dihydropyridine derivatives and their production, formulation and use as pharmaceuticals |
EP0451654A2 (de) * | 1990-04-11 | 1991-10-16 | Bayer Ag | Verwendung von N-alkylierten 1,4-Dihydropyridindicarbonsäureestern als Arzneimittel, neue Verbindungen und Verfahren zu Ihrer Herstellung |
Non-Patent Citations (4)
Title |
---|
ANDREAS M. KNORR: "Influence of nifedipine on experimental arteriosclerosis", CARDIOVASC. DRUGS THER., vol. 4, no. SUP5, 1990, pages 1027 - 1032 * |
GIOVANNI SPERTI ET AL.: "Calcium influx modulates DNA synthesis and proliferation in A7r5 vascular smooth muscle cells", EUR.J.PHARMACOL., vol. 206, no. 4, 1992, pages 279 - 284 * |
PHILIP D. HENRY: "Anti-atherosclerotic effects of calcium antagonists: A brief review", CLIN.INVEST.MED, vol. 10, no. 6, 1987, pages 601 - 605 * |
YON KO ET AL.: "Action of dihydropyridine calcium antagonists on early growth response gene expression and cell growth in vascular smooth muscle cells", J.HYPERTENSION, vol. 11, no. 11, 1993, pages 1171 - 1178 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19741694A1 (de) * | 1997-09-18 | 1999-04-15 | Schering Ag | Verwendung Bis-Amin-Oxim-Derivaten und N¶2¶S¶2¶-Komplexderivaten zur Restenoseprophylaxe |
DE19741694C2 (de) * | 1997-09-18 | 2002-10-31 | Schering Ag | Verwendung von Komplexen, deren Ligand ein Bis-Amin-Oxim-Derivat oder ein N¶2¶S¶2¶-Derivat und deren Zentralatom ein Radionuklid ist |
WO2003053930A1 (en) * | 2001-12-20 | 2003-07-03 | Bayer Healthcare Ag | 1,4-dihydro-1,4-diphenylpyridine derivatives |
US7199136B2 (en) | 2001-12-20 | 2007-04-03 | Bayer Healthcare Ag | 1,4-dihydro-1,4-diphenylpyridine derivatives |
Also Published As
Publication number | Publication date |
---|---|
CZ43896A3 (en) | 1996-05-15 |
BG100367A (en) | 1996-07-31 |
NO960777D0 (no) | 1996-02-26 |
JPH09501923A (ja) | 1997-02-25 |
AU7613594A (en) | 1995-03-21 |
CN1129906A (zh) | 1996-08-28 |
DE4328884A1 (de) | 1995-03-02 |
PL313116A1 (en) | 1996-06-10 |
EP0714301A1 (de) | 1996-06-05 |
HU9600472D0 (en) | 1996-04-29 |
KR960703594A (ko) | 1996-08-31 |
CA2170285A1 (en) | 1995-03-02 |
NO960777L (no) | 1996-04-10 |
HUT75302A (en) | 1997-05-28 |
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