DE1196665B - Process for the preparation of sulfamic acid salts of lincomycin - Google Patents
Process for the preparation of sulfamic acid salts of lincomycinInfo
- Publication number
- DE1196665B DE1196665B DEU10530A DEU0010530A DE1196665B DE 1196665 B DE1196665 B DE 1196665B DE U10530 A DEU10530 A DE U10530A DE U0010530 A DEU0010530 A DE U0010530A DE 1196665 B DE1196665 B DE 1196665B
- Authority
- DE
- Germany
- Prior art keywords
- lincomycin
- preparation
- acid
- carbon atoms
- alkyl group
- 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.)
- Pending
Links
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical class CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 title claims description 24
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 title claims description 23
- 229960005287 lincomycin Drugs 0.000 title claims description 22
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 6
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 title claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
- -1 alkali metal salt Chemical class 0.000 claims description 3
- HHMAJEQKYRNURJ-UHFFFAOYSA-N octadecylsulfamic acid Chemical compound CCCCCCCCCCCCCCCCCC[NH2+]S([O-])(=O)=O HHMAJEQKYRNURJ-UHFFFAOYSA-N 0.000 claims description 3
- 150000008043 acidic salts Chemical class 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- POUMFISTNHIPTI-BOMBIWCESA-N hydron;(2s,4r)-n-[(1r,2r)-2-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide;chloride Chemical compound Cl.CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 POUMFISTNHIPTI-BOMBIWCESA-N 0.000 claims description 2
- 229960001595 lincomycin hydrochloride Drugs 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- QZZDHBAQLLQCGE-UHFFFAOYSA-N octadecyl sulfamate;sodium Chemical compound [Na].CCCCCCCCCCCCCCCCCCOS(N)(=O)=O QZZDHBAQLLQCGE-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- HVWGGPRWKSHASF-UHFFFAOYSA-N Sulfuric acid, monooctadecyl ester Chemical compound CCCCCCCCCCCCCCCCCCOS(O)(=O)=O HVWGGPRWKSHASF-UHFFFAOYSA-N 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- GOYAALBIXFNQOR-UHFFFAOYSA-N hexadecylsulfamic acid Chemical compound CCCCCCCCCCCCCCCCNS(O)(=O)=O GOYAALBIXFNQOR-UHFFFAOYSA-N 0.000 description 1
- ICUNMUFXKHWMAS-BOMBIWCESA-N hexadecylsulfamic acid (2S,4R)-N-[(1R,2R)-2-hydroxy-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide Chemical compound CCCCCCCCCCCCCCCCNS(O)(=O)=O.CCC[C@@H]1C[C@H](N(C)C1)C(=O)N[C@H]([C@@H](C)O)[C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O ICUNMUFXKHWMAS-BOMBIWCESA-N 0.000 description 1
- BJLJBRCPDABXCA-UHFFFAOYSA-N hexyl sulfamate Chemical compound CCCCCCOS(N)(=O)=O BJLJBRCPDABXCA-UHFFFAOYSA-N 0.000 description 1
- YZOHGORKMOMMDA-UHFFFAOYSA-N hexylsulfamic acid Chemical compound CCCCCCNS(O)(=O)=O YZOHGORKMOMMDA-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- AHFAHPJWRNMQST-UHFFFAOYSA-M sodium;n-hexylsulfamate Chemical compound [Na+].CCCCCCNS([O-])(=O)=O AHFAHPJWRNMQST-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/14—Acyclic radicals, not substituted by cyclic structures attached to a sulfur, selenium or tellurium atom of a saccharide radical
- C07H15/16—Lincomycin; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von suIfaminsauren Salzen des Lincomycins Lincomycin ist ein kürzlich entdecktes Antibiotikum, welches eine deutliche Wirksamkeit gegenüber bestimmten grampositiven Organismen, insbesondere Staphylococcus aureus; Diplococcus pneumoniae und ß-hämolytische Streptokokken zeigt. Die Wirksamkeit dieses Antibiotikums .gegen Infektionen bei Menschen und Tieren, die auf Krankheitserreger zurückzuführen sind, ist erwiesen. Der antibiotische Grundstoff und die bisher untersuchten Salze weisen jedoch unangenehme Geschmackseigenschaften auf.Process for the preparation of sulphamic acid salts of lincomycin Lincomycin is a recently discovered antibiotic that has significant effectiveness to certain gram-positive organisms, especially Staphylococcus aureus; Shows Diplococcus pneumoniae and ß-hemolytic streptococci. The effectiveness of this Antibiotic. Against infections in humans and animals that react to pathogens has been proven. The basic antibiotic substance and those investigated so far However, salts have unpleasant taste properties.
Die erfindungsgemäß herstellbaren Lincomycinpräparate weisen diese Nachteile nicht auf. Gegenstand der Erfindung ist die Herstellung von sulfaminsauren Salzen des Lincomycins der allgemeinen Formel . in der Ri und R2 eine Alkylgruppe mit 1 bis 24 Kohlenstoffatomen, R2 darüber hinaus auch Wasserstoff bedeutet. Das Verfahren ist dadurch gekennzeichnet, daß man Lincomycin mit einer Mono- oder Dialkylsulfaminsäure, in welcher die Alkylgruppe 1 bis 24 Kohlenstoffatome enthält, oder ein saures Salz des Lincomycins mit einem Alkalimetallsalz einer Mono-oder Dialkylsulfaminsäure, in der die Alkylgruppe 1 bis 24 Kohlenstoffatome enthält, in an sich bekannter Weise umsetzt. Die Herstellung der Lincomycinbase und des Hydrochlorids werden in der südafrikanischen Patentschrift 2184/62 und in der belgischen Patentschrift 619 645 beschrieben. Die erfindungsgemäß herstellbaren neuen Lincomycinsalze weisen die folgenden Vorteile auf. Sie ermöglichen die Lincomycintherapie in flüssiger Form, wobei der bittere Geschmack weitgehend vermindert oder .ausgeschaltet ist. Außerdem wird die Produktstabilität verbessert, und es wird ein verzögertes Freiwerden des aktiven Medikaments aus diesen Salzen erreicht. Ebenso unerwartet ist der höhere Lincomycin-Blutspiegel, der nach der Verabreichung von Lincomycinmono- und -dialkylsulfamaten gemessen wird, im Vergleich zu dem nach Gaben der Lincomycin-Base und bekannter Lincomycinsalze, z. B. dem Hydrochlorid, gemessenen.The lincomycin preparations which can be produced according to the invention do not have these disadvantages. The invention relates to the preparation of sulfamic acid salts of lincomycin of the general formula. in which Ri and R2 are an alkyl group with 1 to 24 carbon atoms, R2 also denotes hydrogen. The process is characterized in that lincomycin with a mono- or dialkylsulfamic acid in which the alkyl group contains 1 to 24 carbon atoms, or an acidic salt of lincomycin with an alkali metal salt of a mono- or dialkylsulfamic acid in which the alkyl group contains 1 to 24 carbon atoms , implemented in a manner known per se. The preparation of the lincomycin base and the hydrochloride are described in the South African patent specification 2184/62 and in the Belgian patent specification 619,645. The novel lincomycin salts which can be prepared according to the invention have the following advantages. They enable Lincomycin therapy in liquid form, whereby the bitter taste is largely reduced or switched off. In addition, the product stability is improved and a delayed release of the active medicament from these salts is achieved. Just as unexpected is the higher lincomycin blood level, which is measured after administration of lincomycin mono- and dialkylsulfamates, compared to that after administration of lincomycin base and known lincomycin salts, e.g. B. the hydrochloride, measured.
Lincomycin-mono- und -dialkylsulfamate eignen sich besonders zur oralen Verabreichung in Verbindung mit pharmazeutischen Trägern in der Form von Kapseln, Tabletten und Flüssigkeitssuspensionen (einschließlich Sirupe). Beispiel 1 Lincomycin-n-hexylsulfamat 1 g Natrium-n-hexylsulfamat und 2,2 g Lincomycinhydrochlorid wurden in 2,5 ccm Wasser umgesetzt. Nach der Verdünnung mit Aceton und Kühlstellen wurde der erzielte Niederschlag filtriert und getrocknet, so daß man 1,24 g Lincomycin-n-hexylsulfamat mit einem Schmelzpunkt bei 175 bis 195°C erzielte. Beispiel 2 Lincomycin-n-octadecylsulfamat Eine Lösung von 370 mg n-Octadecylsulfaminsäure und 406 mg Lincomycin wurde durch Erhitzen in 10 ccm Alkohol hergestellt. Der entstandene Niederschlag wurde nach dem Abkühlen durch Filtrieren gesammelt, mit Aceton gewaschen und getrocknet, so daß man 630 mg Lincomycin-n-octadecylsulfat mit einem Schmelzpunkt von 188 bis 191 erzielte. Das Infrarotspektrum bestätigte die Struktur.Lincomycin mono- and dialkyl sulfamates are particularly suitable for oral administration in conjunction with pharmaceutical carriers in the form of capsules, tablets and liquid suspensions (including syrups). Example 1 Lincomycin n-hexyl sulfamate 1 g of sodium n-hexyl sulfamate and 2.2 g of lincomycin hydrochloride were reacted in 2.5 cc of water. After dilution with acetone and cooling points, the precipitate obtained was filtered and dried, so that 1.24 g of lincomycin n-hexylsulfamate with a melting point of 175 to 195 ° C. were obtained. Example 2 Lincomycin n-octadecylsulfamate A solution of 370 mg of n-octadecylsulfamic acid and 406 mg of lincomycin was prepared by heating in 10 cc of alcohol. The resulting precipitate was collected by filtration after cooling, washed with acetone and dried to obtain 630 mg of lincomycin n-octadecyl sulfate having a melting point of 188 to 191. The infrared spectrum confirmed the structure.
Beispiel 3 Eine Lösung von 10 g Hexadecylsulfaminsäure in 50 ccm Äthanol wurde unter Erwärmen mit einer Lösung von 13,27 g Lincomycin in 50 ccm .Athanol gemischt. Dann wurde 1 g Aktivkohle zugesetzt und unter Stickstoff filtriert. Das Filtrat kristallisierte sehr rasch. Nach dem Waschen mit Wasser und Trocknen bei 55°C erhielt man 16,(7 g Lincomycinhexadecylsulfamat vom Schmelzpunkt 181 bis 183°C.Example 3 A solution of 10 g of hexadecylsulfamic acid in 50 cc of ethanol was heated with a solution of 13.27 g lincomycin in 50 ccm .Athanol mixed. Then 1 g of activated charcoal was added and the mixture was filtered under nitrogen. That The filtrate crystallized very quickly. After washing with water and dry at 55 ° C., 16 (7 g of lincomycin hexadecyl sulfamate with a melting point of 181 bis 183 ° C.
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1196665XA | 1963-03-04 | 1963-03-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1196665B true DE1196665B (en) | 1965-07-15 |
Family
ID=22385627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEU10530A Pending DE1196665B (en) | 1963-03-04 | 1964-02-26 | Process for the preparation of sulfamic acid salts of lincomycin |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1196665B (en) |
-
1964
- 1964-02-26 DE DEU10530A patent/DE1196665B/en active Pending
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