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
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
• • 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 a new antifibrinolytic compound 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 a new compound of the structure n ucu lu coon and the pharmaceutically acceptable salts thereof. More specifically, it relates to the prevention or treatment of a pathological fibrinolytic state in patients by the oral administration of from 1 to 20 and preferably 2 to 8 mg./kg. of body weight per day of the above compounds for varying periods of treatment.
• fibrinolytic activity results from an overabundance of such activators.
• plasmin fibrinolysin
• activators in the blood and it would appear that excessive fibrinolytic activity results from an overabundance of such activators.
• fibrinolytic state When too much plasmin is present, the clotting system of the blood becomes unbalanced, viable clots cannot be maintained, and hemorrhage may result. This situation is known as a fibrinolytic 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 heartlung and prostate surgery), obstetrical hemorrhage problems, menorrhagia, and many other uses which have been suggested in the literature (e.g. see Nilssen, Acta Medicia Scand. Suppl. 448, volume 180, 1966).
• EACA epsilon aminocaproic acid
• AMCHA trans-4-aminomethylcyclohexane carboxylic acid
• PAMBA 4-aminomethylbenzoic acid
• the new compound of my invention has the general structure ll NCH E cn cooa
• the pharmaceutically acceptable salts of the compound also show antifibrinolytic activity.
• the present invention also provides a process of pre paring a compound of the structure which comprises hydrolyzing a compound of the structure wherein R is an organic radical containing of from 1 to about 10 carbon atoms.
• the hydrolysis is carried out under conventional conditions generally in the presence of an inorganic acid.
• the R groups are either lower al-kyl or benzyl.
• the compound 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 compound are not themselves very active in vitro but the action of enzymes in vivo 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.
• Such amides and esters are to be considered as being within the scope of the present invention since it is actually the present compound which produces the result within the body.
• the compound of this invention can be used in a composition comprising 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
• the pharmaceutically acceptable salts are readily usable, especially in injectable compositions.
• EXAMPLE 1 (A) 4 aminomethylbicyclo [2.2.2]-octane-l-carboxylic acid hydrochloride salt To a solution of 2.80 g. (0.0156 mole) of 4-cyanobicyclo-[2.2.2]-octane-l-carboxylic acid (Roberts et a1. LACS 1953 75, 637) in 100 ml. ethanol is added 5.0 ml. 6 N hydrochloric acid and 500 mg. platinum oxide. During hydrogenation on a Parr apparatus at room temperature and 40 lbs/in. pressure, the theoretical quantity of hydrogen is absorbed during the first half hour. After 2 hours, the hydrogenation is stopped and the reaction mixture filtered through sintered glass to remove the platinum catalyst.
• This crude benzyl ester (3.35 g.) is saponified by stirring overnight in 12 ml. ethanol containing 4.3 ml. 2.0 N NAOH. Removal of the ethanol and acidification of the aqueous solution gives an oil which is extracted into ethyl acetate. The oil is purified by column chromatography on silica gel (benzen-ethyl acetate eluant) to give pure 4-benzamidomethylbicyclo- [2.2.2]-octane-l-acetic acid (700 mg. 23% yield). Because this material could not be obtained in crystalline form, it is hydrolyzed directly without further purification to the amino acid.

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)

Applications Claiming Priority (1)

Publications (1)

Family

ID=25266215

Family Applications (1)

Country Status (10)

Cited By (2)

Families Citing this family (1)

• 1969
  • 1969-06-17 US US834139A patent/US3641129A/en not_active Expired - Lifetime
• 1970
  • 1970-05-25 NL NL7007535A patent/NL7007535A/xx not_active Application Discontinuation
  • 1970-06-02 IL IL34650A patent/IL34650A0/xx unknown
  • 1970-06-12 CH CH890570A patent/CH537365A/de not_active IP Right Cessation
  • 1970-06-15 GB GB1252540D patent/GB1252540A/en not_active Expired
  • 1970-06-15 SE SE08264/70A patent/SE365505B/xx unknown
  • 1970-06-16 FR FR7022080A patent/FR2052979B1/fr not_active Expired
  • 1970-06-16 BE BE752043D patent/BE752043A/xx unknown
  • 1970-06-16 DE DE2029807A patent/DE2029807C3/de not_active Expired
  • 1970-06-16 ZA ZA704089A patent/ZA704089B/xx unknown

Also Published As

Similar Documents