Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
  • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
  • C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates

Definitions

• the present invention relates to new orally effective antidiabetic agents and more particularly to orally efiective biguanide compounds of the tetrahydroisoquinoline series, and to a process of making the same.
• biguanide compounds have antidiabetic properties (see, for instance, Archiv f. exp. Pathol. PharmacoL, vol. 142 (1929), page 290). However, said compounds are unsuitable in the treatment of diabetes mellitus by oral administration because of their high toxicity. Recently, other biguanide compounds have been found to be orally effective antidiabetic agents (Belgian Patent No. 557,985), but they cause nausea and vomiting in a large number of patients, so that they are also too toxic for administration over a prolonged period of time.
• his one object of the present invention to provide new and orally highly eifective antidiabetic biguanide compounds which have a low toxicity combined with a good therapeutical activity.
• Another object of the present invention is to provide a simple and efiective process of making such compounds.
• the new biguanide compounds according to the present invention are prepared according to various methods.
• guanyl tetrahydroisoquinoline may be added to cyanamide which may be substituted, according to the following equation:
• Z-cyano tetrahydroisoquinoline may be reacted with guanidine which may be substituted, according to the following equation:
• Example 1 34 g. of tetrahydroisoquinoline hydrochloride are inti-- mately mixed with 16.8 g. of dicyandiamide. The mixtureis heated in an oil bath of a temperature of 142 C. for 55 minutes. The resulting reaction product is boiled with. cc. of ethanol. After cooling, the solution is filtered; by suction. 34.8 g. of the biguanide compound of Formula II are obtained. Melting point: 226-228 C.
• reaction according to the present invention may be carried out with other alkyl substituted dicyandiamides such as the ethyl, npropyl, isopropyl, n-butyl, isoamyl dicyandiamide and the like. Otherwise the procedure is the same as described in said examples.
• the new tetrahydroisoquinoline biguanide compounds accordingto the present invention are administered in solid form, preferably in shaped form, such as in the form of tablets, pills, dragees, lozenges, and the like shaped preparations, or in powder form, preferably enclosed in gelatin and the like capsules.
• Administration in liquid form such as in the form of emulsion, suspensions, sirups, cough drops, and the like is also possible.
• These solid and liquid preparations are produced in a manner known to the art of compounding and processing pharmaceutical products, whereby the conventional diluting agents, binding agents, lubricants, expanding agents, and the like may be employed.
• the new compounds are preferably administered in the form of their acid addition salts such as the hydrochloride, sulfate, phosphate, nitrate, or the like. Salts with organic acids may also be used such as the salts with acetic acid, citric acid and succinic acid.
• the tetrahydroisoquinoline biguanide compound of the formula 2 1.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

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Family Applications (1)

Country Status (3)

Cited By (13)

• 0
  • NL NL241947D patent/NL241947A/xx unknown
  • NL NL120765D patent/NL120765C/xx active
• 1959
  • 1959-07-10 GB GB23842/59A patent/GB857576A/en not_active Expired
  • 1959-08-06 US US831932A patent/US2951843A/en not_active Expired - Lifetime

Non-Patent Citations (1)

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