Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
  • C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
  • C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
• • 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
  • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents
• • 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
  • A61P9/10—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 invention relates to the compound of the formula
• Chronic obstructive pulmonary diseases such as chronic bronchitis, psoriasis, colitis uicerosa, gastro- or enteropathy induced by non-steroidal anti-inflammatory drugs, Alzheimer's disease, shock, reperfusion damage / ischemia, atherosclerosis, multiple sclerosis.
• the new compound can also be used to treat diseases or conditions in which the passage of cells from the blood via the vascular endothelium into the tissue is important (for example metastasis) or diseases and conditions in which the combination of LTB4 or another molecule (for example 12-HETE) with the LTB4 receptor has an influence on cell proliferation (e.g. chronic myelocytic leukemia).
• diseases or conditions in which the passage of cells from the blood via the vascular endothelium into the tissue is important for example metastasis
• diseases and conditions in which the combination of LTB4 or another molecule (for example 12-HETE) with the LTB4 receptor has an influence on cell proliferation e.g. chronic myelocytic leukemia.
• the new compound can also be used in combination with other active ingredients, such as those used for the same indications, or e.g. with antiallergics, secretolytics, ß2-adrenergics, inhalable steroids, antihistamines and / or PAF antagonists.
• Administration can be topical, oral, transdermal, nasal, parenteral or inhalative.
• the therapeutic or prophylactic dose depends on the patient's body weight and the nature and seriousness of the disease. When used orally, the dose is between 10 and 500 mg, preferably between 20 and 250 mg. When used by inhalation, the patient is given between about 0.5 and 25, in particular between 2 and 20, mg of active ingredient.
• the new compounds can be administered in customary preparations, for example as tablets, dragées, capsules, wafers, powders, granules, solutions, emulsions, syrups, inhalation aerosols, ointments, suppositories.
• Active ingredient according to the invention 20 parts by weight
• the ingredients are processed in the usual way to tablets of 500 mg weight. If desired, the active substance content can be increased or decreased and the amount of glucose reduced or increased accordingly. Suppositories
• composition active ingredient according to the invention 100 parts by weight of lactose, powdered 45 parts by weight of cocoa butter 1555 parts by weight
• the ingredients are processed in the usual way to form suppositories weighing 1.7 g.
• Micronized active ingredient powder (compound of formula I; particle size approx. 0.5 to 7 ⁇ m) is filled into hard gelatin capsules in an amount of 5 mg, optionally with the addition of micronized lactose.
• the powder is extracted from conventional inhalation devices, e.g. according to DE-A 3 345 722, inhaled.
• the new compound shows a surprisingly superior activity compared to the known LTB4 antagonists. This is expressed, for example, in the test result for the LTB4-induced neutrophil accumulation on the mouse ear.
• the ED50 value of 0.05 mg / kg obtained is far lower than the values found for structurally similar compounds
• the new connection can be established using standard methods:
• reaction is conveniently carried out in a polar solvent such as
• Ethanol, glacial acetic acid or dimethylformamide at room temperature up to 60 ° C and at normal pressure up to 5 bar.
• Raney nickel or platinum are used as catalysts.
• the amidoxime used as the starting material is obtained, for example, by reacting the corresponding nitrile with hydroxylamine.
• Compound I can also be produced from partial structures with an amidine group already present.
• a compound of formula III is reacted with the phenol of formula IV or the phenol of formula V with a compound of formula VI:
• the alkyl radicals R2 are generally those radicals having up to 6 carbon atoms. Phenyl or tolyl is preferably used as the aryl.
• the methanol is distilled off, the residue is taken up in 2000 ml of ethyl acetate and extracted twice with 500 ml of water each time.
• the ethyl acetate is distilled off and the residue is recrystallized from 300 ml of ethanol.
• the product is dissolved hot in 200 ml of ethanol and slowly cooled to room temperature overnight.
• the crystals are filtered off, washed with 50 ml of cold ethanol and dried. Yield: 69 g; Melting point 160 ° C.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• Public Health (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Biomedical Technology (AREA)
• Pulmonology (AREA)
• Cardiology (AREA)
• Heart & Thoracic Surgery (AREA)
• Neurosurgery (AREA)
• Neurology (AREA)
• Immunology (AREA)
• Rheumatology (AREA)
• Pain & Pain Management (AREA)
• Hospice & Palliative Care (AREA)
• Vascular Medicine (AREA)
• Urology & Nephrology (AREA)
• Psychiatry (AREA)
• Dermatology (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (3)

Publications (1)

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• 1994
  • 1994-07-13 DE DE4424714A patent/DE4424714A1/de not_active Withdrawn
• 1995
  • 1995-06-03 MX MX9700245A patent/MX9700245A/es unknown
  • 1995-06-03 PL PL95318114A patent/PL318114A1/xx unknown
  • 1995-06-03 HU HU9700060A patent/HUT76827A/hu unknown
  • 1995-06-03 JP JP8504619A patent/JPH10502646A/ja active Pending
  • 1995-06-03 KR KR1019970700123A patent/KR970704674A/ko not_active Application Discontinuation
  • 1995-06-03 CN CN95194047A patent/CN1152303A/zh active Pending
  • 1995-06-03 CZ CZ9782A patent/CZ8297A3/cs unknown
  • 1995-06-03 WO PCT/EP1995/002113 patent/WO1996002496A1/de not_active Application Discontinuation
  • 1995-06-03 AU AU27368/95A patent/AU2736895A/en not_active Abandoned
  • 1995-06-03 CA CA002194886A patent/CA2194886A1/en not_active Abandoned
  • 1995-06-03 EE EE9700065A patent/EE9700065A/xx unknown
  • 1995-06-03 SK SK18-97A patent/SK1897A3/sk unknown
  • 1995-06-03 BR BR9508395A patent/BR9508395A/pt unknown
  • 1995-06-03 US US08/765,527 patent/US5686496A/en not_active Expired - Fee Related
  • 1995-06-03 EP EP95922492A patent/EP0770058A1/de not_active Withdrawn
  • 1995-06-27 HR HRP4424714.1A patent/HRP950363A2/xx not_active Application Discontinuation
  • 1995-07-06 YU YU45395A patent/YU45395A/sh unknown
  • 1995-07-11 PE PE1995273520A patent/PE35196A1/es not_active Application Discontinuation
  • 1995-07-12 IL IL11457295A patent/IL114572A0/xx unknown
  • 1995-07-12 CO CO95030620A patent/CO4410185A1/es unknown
  • 1995-07-12 ZA ZA955781A patent/ZA955781B/xx unknown
• 1997
  • 1997-01-04 BG BG101104A patent/BG101104A/xx unknown
  • 1997-01-10 FI FI970095A patent/FI970095A0/fi not_active Application Discontinuation
  • 1997-01-10 NO NO970123A patent/NO970123L/no unknown

Non-Patent Citations (1)

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