US2951843A - Tetrahydrosoquinoline biguanides - Google Patents
Tetrahydrosoquinoline biguanides Download PDFInfo
- Publication number
- US2951843A US2951843A US831932A US83193259A US2951843A US 2951843 A US2951843 A US 2951843A US 831932 A US831932 A US 831932A US 83193259 A US83193259 A US 83193259A US 2951843 A US2951843 A US 2951843A
- Authority
- US
- United States
- Prior art keywords
- tetrahydroisoquinoline
- compounds
- biguanide
- tetrahydrosoquinoline
- biguanides
- 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.)
- Expired - Lifetime
Links
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.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE857576X | 1958-08-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
US2951843A true US2951843A (en) | 1960-09-06 |
Family
ID=6789605
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US831932A Expired - Lifetime US2951843A (en) | 1958-08-06 | 1959-08-06 | Tetrahydrosoquinoline biguanides |
Country Status (3)
Country | Link |
---|---|
US (1) | US2951843A (xx) |
GB (1) | GB857576A (xx) |
NL (2) | NL120765C (xx) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3157573A (en) * | 1962-12-18 | 1964-11-17 | Hoffmann La Roche | Antihypertensive 3, 4-dihydro-2(1h)-isoquinolinecarboxamidine |
US3252989A (en) * | 1963-02-04 | 1966-05-24 | American Home Prod | Pyrazole-1-carboxamidines |
US3291799A (en) * | 1964-09-21 | 1966-12-13 | Hoffmann La Roche | Isoquinoline carboxamidine |
US3299078A (en) * | 1962-10-01 | 1967-01-17 | Smith Kline French Lab | Pyrido [3', 4': 4, 5] pyrrolo [3, 2, 1-hi] indoles and-[3, 2, 1-ij] quinolines |
US3314963A (en) * | 1962-07-23 | 1967-04-18 | Pfizer & Co C | Azabenzocycloalkane-n-carboxamidines |
US3505336A (en) * | 1968-05-06 | 1970-04-07 | Sterling Drug Inc | 3,4-dihydro-2-(1h)-isoquinolinecarboxamidoximes and lower-alkanoates |
US3539576A (en) * | 1967-07-17 | 1970-11-10 | American Home Prod | 1,2,3,7,8,12b-hexahydrobenzo(1,2)cyclohepta(3,4,5 - d,e) isoquinolinomethyleneamidoximes and esters thereof |
US5612332A (en) * | 1984-03-19 | 1997-03-18 | Alteon Inc. | Di- and triaminoguanidines, and methods of use |
US5852009A (en) * | 1984-03-19 | 1998-12-22 | The Rockefeller University | Compositions, including pharmaceutical compositions, for inhibiting the advanced glycosylation of proteins, and therapeutic methods based thereon |
US5850840A (en) * | 1995-11-15 | 1998-12-22 | Alteon Inc. | Methods for measurement and treatment predicated on the presence of advanced glycosylation endproducts in tobacco and its combustion byproducts |
US5877217A (en) * | 1995-12-26 | 1999-03-02 | Alteon Inc. | N-acylaminoalkyl-hydrazinecarboximidamides |
US6110968A (en) * | 1995-12-26 | 2000-08-29 | The Picower Institute For Medical Research | Methods for treatment predicated on the presence of advanced glycosylation endproducts in tobacco and its combustion byproducts |
EP2742020A4 (en) * | 2011-08-08 | 2015-03-11 | Hanall Biopharma Co Ltd | N1-CYCLIC AMIN-N5-SUBSTITUTED BIGUANIDE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITION THEREWITH |
-
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)
Title |
---|
None * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3314963A (en) * | 1962-07-23 | 1967-04-18 | Pfizer & Co C | Azabenzocycloalkane-n-carboxamidines |
US3299078A (en) * | 1962-10-01 | 1967-01-17 | Smith Kline French Lab | Pyrido [3', 4': 4, 5] pyrrolo [3, 2, 1-hi] indoles and-[3, 2, 1-ij] quinolines |
US3157573A (en) * | 1962-12-18 | 1964-11-17 | Hoffmann La Roche | Antihypertensive 3, 4-dihydro-2(1h)-isoquinolinecarboxamidine |
US3252989A (en) * | 1963-02-04 | 1966-05-24 | American Home Prod | Pyrazole-1-carboxamidines |
US3291799A (en) * | 1964-09-21 | 1966-12-13 | Hoffmann La Roche | Isoquinoline carboxamidine |
US3539576A (en) * | 1967-07-17 | 1970-11-10 | American Home Prod | 1,2,3,7,8,12b-hexahydrobenzo(1,2)cyclohepta(3,4,5 - d,e) isoquinolinomethyleneamidoximes and esters thereof |
US3505336A (en) * | 1968-05-06 | 1970-04-07 | Sterling Drug Inc | 3,4-dihydro-2-(1h)-isoquinolinecarboxamidoximes and lower-alkanoates |
US5612332A (en) * | 1984-03-19 | 1997-03-18 | Alteon Inc. | Di- and triaminoguanidines, and methods of use |
US5852009A (en) * | 1984-03-19 | 1998-12-22 | The Rockefeller University | Compositions, including pharmaceutical compositions, for inhibiting the advanced glycosylation of proteins, and therapeutic methods based thereon |
US6114323A (en) * | 1984-03-19 | 2000-09-05 | The Rockefeller University | Methods for inhibiting the advanced glycosylation of proteins |
US5850840A (en) * | 1995-11-15 | 1998-12-22 | Alteon Inc. | Methods for measurement and treatment predicated on the presence of advanced glycosylation endproducts in tobacco and its combustion byproducts |
US5877217A (en) * | 1995-12-26 | 1999-03-02 | Alteon Inc. | N-acylaminoalkyl-hydrazinecarboximidamides |
US6110968A (en) * | 1995-12-26 | 2000-08-29 | The Picower Institute For Medical Research | Methods for treatment predicated on the presence of advanced glycosylation endproducts in tobacco and its combustion byproducts |
EP2742020A4 (en) * | 2011-08-08 | 2015-03-11 | Hanall Biopharma Co Ltd | N1-CYCLIC AMIN-N5-SUBSTITUTED BIGUANIDE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITION THEREWITH |
US9321742B2 (en) | 2011-08-08 | 2016-04-26 | Immunomet Therapeutics Inc. | N1-cyclic amine-N5-substituted biguanide derivatives, methods of preparing the same and pharmaceutical composition comprising the same |
Also Published As
Publication number | Publication date |
---|---|
NL120765C (xx) | |
NL241947A (xx) | |
GB857576A (en) | 1960-12-29 |
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