DE834247C - Process for the preparation of therapeutically effective salts of nicotinic acid - Google Patents
Process for the preparation of therapeutically effective salts of nicotinic acidInfo
- Publication number
- DE834247C DE834247C DEL2882A DEL0002882A DE834247C DE 834247 C DE834247 C DE 834247C DE L2882 A DEL2882 A DE L2882A DE L0002882 A DEL0002882 A DE L0002882A DE 834247 C DE834247 C DE 834247C
- Authority
- DE
- Germany
- Prior art keywords
- nicotinic acid
- salts
- preparation
- parts
- therapeutically effective
- 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
Links
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 title claims description 34
- 235000001968 nicotinic acid Nutrition 0.000 title claims description 14
- 239000011664 nicotinic acid Substances 0.000 title claims description 14
- 229960003512 nicotinic acid Drugs 0.000 title claims description 13
- 150000003839 salts Chemical class 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 2
- -1 R.3 and R Chemical group 0.000 claims description 3
- 230000001387 anti-histamine Effects 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 150000007514 bases Chemical class 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 230000000694 effects Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- 206010016334 Feeling hot Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012262 resinous product Substances 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- KFLRWGSAMLBHBV-UHFFFAOYSA-M sodium;pyridine-3-carboxylate Chemical compound [Na+].[O-]C(=O)C1=CC=CN=C1 KFLRWGSAMLBHBV-UHFFFAOYSA-M 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von therapeutisch wirksamen Salzen der Nicotinsäure Salze aus Nicutiiisäurc und stickstoffhaltigen, organischen, basischen Verbindungen, z. B. Piperidin, sind bekannt. Es ist ferner bekannt, daß Nicotinsäure eine erweiternde Wirkung auf die Blutgefälle ausübt. Diese Wirkung ist jedoch sehr vorübergehender Art, da die Nicotinsäure im Körper rasch durch Methylierung oder durch Paarung mit Glykokoll unwirksam gemacht wird. Außerdem führt die cutane Anwendung der Nicotinsäure zii unangenehmen Nebenwirkungen, die sich in Form vom Brennen, Jucken und Rötung ; U ßern. Es wurde nun überraschenderweise gefunden, daß man zu neuen Verbindungen gelangen kann, die die erwähnten unerwünschten Nebenwirkungen der Nikotins:itire nicht oder in nur unerheblichem :Maße besitzen, wenn niair die Nicotinsäure mit antihistaminisch wirksamen, hochmolekularen, organischen, basischen Verbindungen der allgemeinen Formeln worin R, und R2 Aryl- oder Aralkylreste bzw. helerocyclische Reste, R;, und R; Alkyl- oder Cycloalkylreste oder gemeinsam unter Einbeziehung des Stickstoffatoms einen heterocyclischen Rest bedeuten, umsetzt. Ebensogut kann man auch die Salze der Nicotinsäure, z. B. die Alkalisalze, mit den Salzen der erwähnten basischen Verbindungen, z. B. Hydrochloriden, Hydrobromiden oder Sulfaten, zur Umsetzung bringen.Process for the preparation of therapeutically active salts of nicotinic acid Salts from nicutiiic acid and nitrogen-containing, organic, basic compounds, e.g. B. piperidine are known. It is also known that nicotinic acid has a dilating effect on blood gradients. However, this effect is very temporary, as nicotinic acid in the body is quickly rendered ineffective by methylation or by pairing with glycocolla. In addition, the cutaneous application of nicotinic acid leads to unpleasant side effects in the form of burning, itching and reddening ; U uter. It has now been found, surprisingly, that new compounds can be obtained which do not, or only to a negligible extent, have the undesirable side effects of nicotine mentioned, if nicotinic acid is not used with antihistaminic, high molecular weight, organic, basic compounds of the general formulas wherein R, and R2 are aryl or aralkyl radicals or helerocyclic radicals, R ;, and R; Alkyl or cycloalkyl radicals or together with the inclusion of the nitrogen atom mean a heterocyclic radical. The salts of nicotinic acid, e.g. B. the alkali salts, with the salts of the basic compounds mentioned, for. B. hydrochlorides, hydrobromides or sulfates, bring to implementation.
Die Umsetzung selbst kann entweder durch Vereinigen der Komponenten selbst oder aber in geeigneten Lösungsmitteln, z. B. Methanol, Äthanol usw., gegebenenfalls auch in Wasser, durchgeführt werden. '.Ulan erhält die nicotinsauren Salze der erwähnten hochmolekularen, antihistaminisch wirksamen, organischen, basischen Verbindungen häufig in Form öliger oder harziger Produkte, die eine verhältnismäßig geringe Neigung zur Kristallisation aufweisen, insbesondere, solange sie noch SpurenLösungsmittel enthalten. Die kristallisierten Produkte lassen sich durch Umkristallisieren aus geeigneten Lösungsmitteln weiter reinigen.The implementation itself can either be done by combining the components themselves or in suitable solvents, e.g. B. methanol, ethanol, etc., optionally also in water. '.Ulan receives the nicotinic acid salts of the aforementioned high-molecular, antihistaminic, organic, basic compounds often in the form of oily or resinous products that have a relatively low tendency to crystallize, especially as long as they still contain trace solvents contain. The crystallized products can be removed by recrystallization further clean with suitable solvents.
Die auf diese Weise erhaltenen nicotinsauren Salze der erwähnten organischen, basischen Verbindungen stellen therapeutisch wertvolle Produkte dar, die im Gegensatz zur Nicotinsäure eine lang anhaltende Wirksamkeit besitzen und frei von deren unerwünschten Nebenwirkungen sind.The nicotinic acid salts of the mentioned organic, basic compounds represent therapeutically valuable products, which in contrast to nicotinic acid have a long-lasting effectiveness and free from its undesirable Side effects are.
Insbesondere verursachen sie bei cutaner- Anwendung weder Brennen noch Jucken, und selbst die Rötung der Haut wird erheblich herabgesetzt. Als erwünschte Erscheinung rufen sie ein anhaltendes Wärmegefühl hervor. Beispiele i. In einer Lösung von 22,4 Teilen Phenylbenzylaminoäthylen-N-pyrrolidin in 2o Teilen Äthanol löst man unter leichtem Erwärmen 9,8 Teile Nicotinsäure. Nach Abdampfen des Alkohols im Vakuum erhält man das nicotinsaure Salz als Sirupöse Masse, die nach längerem Stehen oder nach Animpfen kristallisiert. Das Salz löst sich leicht in Methanol, Äthanol und heißem Aceton.In particular, they do not cause any burning sensation when used in cutaneous tissue itching, and even the reddening of the skin is considerably reduced. As desired Appearance they evoke a persistent feeling of warmth. Examples i. In a Solution of 22.4 parts of phenylbenzylaminoethylene-N-pyrrolidine in 20 parts of ethanol 9.8 parts of nicotinic acid are dissolved with gentle heating. After the alcohol has evaporated in a vacuum, the nicotinic acid salt is obtained as a syrupy mass, which after a long time Standing or crystallized after inoculation. The salt easily dissolves in methanol, Ethanol and hot acetone.
Das gleiche Salz erhält man, wenn man die genannten Mengen Phenylbenzylaminoäthylen-N-pyrrolidin und Nicotinsäure im Mörser gründlich verreibt. Das Reaktionsprodukt zeichnet sich in diesem Falle durch eine merklich größere Kristallisationsfreudigkeit aus.The same salt is obtained if the stated amounts of phenylbenzylaminoethylene-N-pyrrolidine are used and nicotinic acid thoroughly rubbed in a mortar. The reaction product stands out in this case by a noticeably greater tendency to crystallize.
2. In einer siedenden Lösung von 14,3 Teilen Natriumnicotinat in 35o
Teildn Methanol löst man 31,6 Teile Phenyibenzylaminoäthylen-N-pyrroliditihydrochlorid.
Man engt auf etwa % ein und filtriert vom ausgeschiedenen Natriumchlorid ab. Aus
der Restlösung erhält man durch weiteres Eindampfen das nicotinsaure Salz der erwähnten
organischen, basischen Verbindung.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEL2882A DE834247C (en) | 1950-06-29 | 1950-06-29 | Process for the preparation of therapeutically effective salts of nicotinic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEL2882A DE834247C (en) | 1950-06-29 | 1950-06-29 | Process for the preparation of therapeutically effective salts of nicotinic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE834247C true DE834247C (en) | 1952-03-17 |
Family
ID=7255967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEL2882A Expired DE834247C (en) | 1950-06-29 | 1950-06-29 | Process for the preparation of therapeutically effective salts of nicotinic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE834247C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1227459B (en) * | 1962-12-14 | 1966-10-27 | Biochemie Gmbh | Process for the preparation of a new salt of nicotinic acid |
-
1950
- 1950-06-29 DE DEL2882A patent/DE834247C/en not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1227459B (en) * | 1962-12-14 | 1966-10-27 | Biochemie Gmbh | Process for the preparation of a new salt of nicotinic acid |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE29724281U1 (en) | 4-phenylpiperidine compounds | |
| DE1545575B1 (en) | N, N'-bis [3- (3 ', 4', 5'-trimethoxybenzoyloxy) propyl] homopiperazine | |
| DE834247C (en) | Process for the preparation of therapeutically effective salts of nicotinic acid | |
| DE2641896A1 (en) | QUATERNAERE AMMONIUM COMPOUND AND THEIR USE | |
| DE540697C (en) | Process for the preparation of diamines acylated on one side | |
| DE2427272C3 (en) | 1- (2- (β-Naphthyloxy) ethyl) -3-methyl-pyrazolone- (5), method and use as an antithrombotic | |
| DE2122070A1 (en) | 1 Veratryl 4 methyl 5 ethyl 7,8 dimethoxy 2,3 diazabicyclo square brackets to 5,4,0 square brackets to undeca pentaen (1,3,6,8,10) and its use | |
| DE632257C (en) | Process for the production of Abkoemmlingen the pyrazine monocarboxylic acid | |
| DE743467C (en) | Process for the preparation of nicotinic acid alkamine esters | |
| DE887649C (en) | Process for the preparation of unsaturated amines suitable as antispasmodics | |
| DE1044084B (en) | Process for the preparation of new piperidine compounds | |
| DD262860A5 (en) | PROCESS FOR THE PREPARATION OF A NICOTINSAE DERIVATIVE | |
| DE568549C (en) | Process for the preparation of 2-alkoxy-5-nitropyridines | |
| DE629054C (en) | Process for the production of pellets of tertiary aliphatic amino acids | |
| AT230372B (en) | Process for the preparation of new 4-amino-1-phenyl-2,3-dimethyl-pyrazolone derivatives | |
| AT228199B (en) | Process for the preparation of a new imidazoline derivative and its salts | |
| DE488681C (en) | Process for the preparation of imidazole derivatives | |
| DE1418540C (en) | Process for the preparation of 1,3,2 dioxaborolanes or 1,3,2 dioxabonnanes | |
| AT78703B (en) | Process for the preparation of therapeutically valuable compounds of the alkaloids of the morphine group. | |
| AT144906B (en) | Process for the preparation of compounds from C.C-disubstituted barbituric acids and pyrazolone derivatives. | |
| DE1060866B (en) | Process for the preparation of therapeutically useful pyrazolone derivatives | |
| DE1795532C3 (en) | Process for the preparation of dihydro dysergamine derivatives excretion from 1470217 | |
| DE1670378C (en) | Process for the preparation of the salt from 4-n-butyl-3,5-dioxo-1,2-diphenylpyrazolidine and the beta-diethylamino-ethylamide of p-chlorophenoxyacetic acid | |
| CH429734A (en) | Process for the preparation of quinolizine derivatives | |
| AT275519B (en) | Process for the preparation of new 1,4-dihydropyridine derivatives |