EP0714301A1 - Utilisation comme medicaments d'esters d'acide 1-4-dihydropyridin dicarboxylique n-alkyles - Google Patents

Utilisation comme medicaments d'esters d'acide 1-4-dihydropyridin dicarboxylique n-alkyles

Info

Publication number
EP0714301A1
EP0714301A1 EP94926199A EP94926199A EP0714301A1 EP 0714301 A1 EP0714301 A1 EP 0714301A1 EP 94926199 A EP94926199 A EP 94926199A EP 94926199 A EP94926199 A EP 94926199A EP 0714301 A1 EP0714301 A1 EP 0714301A1
Authority
EP
European Patent Office
Prior art keywords
general formula
carbon atoms
compounds
medicaments
alkylated
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.)
Withdrawn
Application number
EP94926199A
Other languages
German (de)
English (en)
Inventor
Siegfried Zaiss
Dieter Neuser
Johannes-Peter Stasch
Siegfried Goldmann
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.)
Bayer AG
Original Assignee
Bayer AG
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 Bayer AG filed Critical Bayer AG
Publication of EP0714301A1 publication Critical patent/EP0714301A1/fr
Withdrawn legal-status Critical Current

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)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Urology & Nephrology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation comme médicaments anti-athérosclérose, d'esters d'acide 1-4-dihydropyridin dicarboxylique N-alkylés partiellement connus de la formule (I), dans laquelle R1 à R6 ont la notation mentionnée dans la description. L'invention concerne notamment leur utilisation pour assurer la prophylaxie de la resténose après des angioplasties et des interventions chirurgicales vasculaires.
EP94926199A 1993-08-27 1994-08-16 Utilisation comme medicaments d'esters d'acide 1-4-dihydropyridin dicarboxylique n-alkyles Withdrawn EP0714301A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4328884 1993-08-27
DE4328884A DE4328884A1 (de) 1993-08-27 1993-08-27 Verwendung von N-alkylierten 1,4-Dihydropyridincarbonsäureestern als Arzneimittel
PCT/EP1994/002723 WO1995005823A1 (fr) 1993-08-27 1994-08-16 Utilisation comme medicaments d'esters d'acide 1-4-dihydropyridin dicarboxylique n-alkyles

Publications (1)

Publication Number Publication Date
EP0714301A1 true EP0714301A1 (fr) 1996-06-05

Family

ID=6496196

Family Applications (1)

Application Number Title Priority Date Filing Date
EP94926199A Withdrawn EP0714301A1 (fr) 1993-08-27 1994-08-16 Utilisation comme medicaments d'esters d'acide 1-4-dihydropyridin dicarboxylique n-alkyles

Country Status (13)

Country Link
EP (1) EP0714301A1 (fr)
JP (1) JPH09501923A (fr)
KR (1) KR960703594A (fr)
CN (1) CN1129906A (fr)
AU (1) AU7613594A (fr)
BG (1) BG100367A (fr)
CA (1) CA2170285A1 (fr)
CZ (1) CZ43896A3 (fr)
DE (1) DE4328884A1 (fr)
HU (1) HUT75302A (fr)
NO (1) NO960777L (fr)
PL (1) PL313116A1 (fr)
WO (1) WO1995005823A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
ES2271365T3 (es) 2001-12-20 2007-04-16 Bayer Healthcare Ag Derivados de 1,4-dihidro-1,4-difenilpiridina.
US10258498B2 (en) * 2011-11-24 2019-04-16 Richter Gedeon Nyrt. 1,4-dihydropyridine derivatives with Hsp modulating activity

Family Cites Families (3)

* Cited by examiner, † Cited by third party
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
EP0169009A3 (fr) * 1984-07-17 1988-08-31 FISONS plc Dérivés de dihydropyridine et leur préparation, leur formulation et leur utilisation comme produits pharmaceutiques
DE4011695A1 (de) * 1990-04-11 1991-10-17 Bayer Ag Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsaeureestern als arzneimittel, neue verbindungen und verfahren zu ihrer herstellung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9505823A1 *

Also Published As

Publication number Publication date
AU7613594A (en) 1995-03-21
JPH09501923A (ja) 1997-02-25
HUT75302A (en) 1997-05-28
WO1995005823A1 (fr) 1995-03-02
HU9600472D0 (en) 1996-04-29
CA2170285A1 (fr) 1995-03-02
NO960777D0 (no) 1996-02-26
CZ43896A3 (en) 1996-05-15
DE4328884A1 (de) 1995-03-02
BG100367A (en) 1996-07-31
CN1129906A (zh) 1996-08-28
PL313116A1 (en) 1996-06-10
KR960703594A (ko) 1996-08-31
NO960777L (no) 1996-04-10

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