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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid

Definitions

• This invention relates to new anti-fibrinolytic compounds and to a method of counteracting certain hemorrhagic conditions and other disorders resulting from a pathological fibrinolytic state in patients. More specifically, this invention relates to the new compound 4-aminomethylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, having the structure:
• This compound is useful lathe prevention or treatment of a pathological fibrinolytic, state in mammals including persons and animals, by the'oral administration of from 1 to 20 and preferably 2 to 8 mg./kg. of body weight per day of the above compound for varying periods of treatment.
• fibrin deposits in mammals is due to their lysis by the enzyme plasmin (fibrinolysin) which is formed in the blood from plasminogen, also present in the blood.
• plasmin fibrinogen
• This conversion from plasminogen to plasmin is promoted by activators in the blood and it would appear that excessive fibrinolytic activity results from an over-abundance of such activators.
• activators in the blood and it would appear that excessive fibrinolytic activity results from an over-abundance of such activators.
• the clotting system of the blood becomes unbalanced, viable clots cannot be maintained, and hemorrhage may result. This situation is known as a fib'rinolytic state.
• Other enzyme systems i.e., the kallikreins, complement
• antifibrinolytic agents i.e. drugs which will inhibit the activation of plasminogen to form plasmin.
• antifibrinolytic agents are believed to interfere with the function of the activators of converting plasminogen to plasmin.
• the clinical uses of such drugs include their administration to persons undergoing various kinds of surgery (such as heart-lung and prostate surgery), obstetrical hemorrhage problems, menorrhagia, and many other uses which have been suggested in the literature (e.g. see Nilssen, Acta Medica Scand. Suppl. 448, volume 180, 1966.)
• EACA epsilon aminocaproic acid
• AMCHA trans-4-aminomethylcyclohexane carboxylic acid
• PAMBA 4-aminomethylbenzoic acid
• the invention can 'be illustrated by the following example.
• An NMR spectrum (D 0) exhibited the expected absorptions: Complex multiplet 1.0-2.0 p.p.m. (8 protons, nucleus); singlet, 3.12 p.p.m. (2 protons, CH N); AB quartette, 6.32 p.p.m. (1:8.5 c.p.s) (2 protons, vinyl.).
• carboxylic ester derivatives of (5) may be prepared by direct esterification of the amino acid such as by the use of alcoholic hydrogen chloride or thionyl chloride followed by alcohol.
• alkanoyl amino derivatives of (5 are prepared by acylation of the amino acids.
• the compound of this invention is used in the method of this invention by either oral or intravenous administration, although the oral route is preferred.
• the esters and amides of this class of compounds are not themselves very active in vitro but the action of enzymes in vivo may cause the slow liberation of the highly active amino acids, thus providing a prolonged availability of the drug in the body. This is important because of the tendency of these drugs to be swiftly eliminated in the urine.
• the compound of this invention can be used in any pharmaceutically acceptable carrier, in the form of pills, tablets or capsules.
• pharmaceutically acceptable salts both of the amino group-such as the hydrochloride, hydrobromide, sulfate, citrate, tartrate, etc. and of the carboxy group, such as the alkali metal, alkaline earth metal, etc., salts) are readily usable, especially in injectable compositions.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=24847119

Family Applications (1)

Country Status (6)

Cited By (4)

• 1968
  • 1968-02-28 US US708769A patent/US3526657A/en not_active Expired - Lifetime
• 1969
  • 1969-02-13 NL NL6902277.A patent/NL158783B/nl not_active IP Right Cessation
  • 1969-02-18 CH CH242369A patent/CH510639A/de not_active IP Right Cessation
  • 1969-02-19 FR FR6904139A patent/FR2002745A1/fr not_active Withdrawn
  • 1969-02-24 GB GB9739/69A patent/GB1219387A/en not_active Expired
  • 1969-02-26 BR BR206664/69A patent/BR6906664D0/pt unknown

Non-Patent Citations (1)

Also Published As

Similar Documents