CH438271A - Process for the preparation of hydroxycinnamic acid derivatives - Google Patents
Process for the preparation of hydroxycinnamic acid derivativesInfo
- Publication number
- CH438271A CH438271A CH817264A CH817264A CH438271A CH 438271 A CH438271 A CH 438271A CH 817264 A CH817264 A CH 817264A CH 817264 A CH817264 A CH 817264A CH 438271 A CH438271 A CH 438271A
- Authority
- CH
- Switzerland
- Prior art keywords
- solvent
- caffeic acid
- preparation
- piperidine
- piperazine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 7
- NGSWKAQJJWESNS-ZZXKWVIFSA-N trans-4-coumaric acid Chemical class OC(=O)\C=C\C1=CC=C(O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-N 0.000 title claims description 4
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 claims description 29
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 claims description 13
- 235000004883 caffeic acid Nutrition 0.000 claims description 13
- 229940074360 caffeic acid Drugs 0.000 claims description 13
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002244 precipitate Substances 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 5
- 229960005141 piperazine Drugs 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- -1 bis (3,4-dihydroxycinnamate) piperazine Chemical compound 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PFCBHFDNVFQUJI-UHFFFAOYSA-N 3-methylbut-2-en-1-amine Chemical compound CC(C)=CCN PFCBHFDNVFQUJI-UHFFFAOYSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- 229940000681 5-hydroxytryptophan Drugs 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
- 229960003506 piperazine hexahydrate Drugs 0.000 description 1
- AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
- C07C59/52—Unsaturated compounds containing hydroxy or O-metal groups a hydroxy or O-metal group being bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical 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)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Procédé de préparation de dérivés de l'acide hydroxycinnamique
La présente invention concerne un procédé de préparation de médicaments qui ont la propriété d'inhiber les enzymes qui provoquent la décarboxylation de la 3,4-dihydroxyphénylalanine (L. Dopa) et du 5-hydroxytryptophane.
I1 s'agit de dérivés de l'acide hydroxy-cinnamique ayant les formules suivantes:
EMI1.1
dans lesquelles:
R, est: CssHSN (pyridine) ou
C5H11N (pipéridine) ou
C4HgNO (morpholine),
et R2 est: C4HtoN2 (pipérazine).
Le procédé suivant l'invention de préparation de ces composés est caractérisé en ce qu'on dissout ou met en suspension de l'acide caféique dans un solvant, en ce qu'on ajoute ensuite en quantité équimoléculaire par rapport à l'acide caféique de la pyridine, de la pipéridine, de la pipérazine ou de la morpholine en solution dans le mme solvant que celui dans lequel on a dissous ou mis en suspension l'acide caféique, et en ce qu'on recueille, lave, essore et sèche le précipité formé.
Si le solvant est l'acétone, on dissout l'acide caféique à chaud dans ce solvant et l'on obtient un composé de formule 1.
Si le solvant est l'alcool absolu, on met l'acide caféique en suspension à froid dans ce solvant et l'on obtient un composé de formule 2.
On va décrire plus particulièrement le mode de préparation des composés suivants:
1/ 3,4-dihydroxycinnamate de pipéridine (ou caféate de pipéridine)
C14H10O4N (dénommé PC 63-1)
EMI1.2
2/ bis (3,4-dihydroxycinnamate) de pipérazine (ou dicaféate de pipérazine) C22H26O8N2 (dénommé PC 62-15)
EMI1.3
Procédés de préparation et caractéristiques
physicochimiques
a) 3,4-dihydroxycinnamate de pipéridine (caféate de pipéridine) ou PC 63-1.
Dissoudre 9 g d'acide caféique dans 320 ml d'acétone à chaud et filtrer. A la solution ainsi obtenue, refroidie et agitée, on ajoute goutte à goutte la dilution pipéridinique (24,6 mi de pipéridine et 15 mi d'acétone).
I1 se forme alors un produit visqueux qui ne tarde pas à se solidifier par trituration à l'aide d'un agitateur en verre.
Le précipité obtenu est filtré, lavé avec 4 fois 10 ml d'acétone puis séché sous vide sulfurique.
On obtient ainsi une poudre jaunâtre, de point de fusion (PF) 1060 C, très soluble dans Peau, peu soluble dans l'alcool absolu, soluble dans l'alcool à 95 , soluble à froid dans NaOH n en donnant une solution jaune-verdâtre virant ensuite au brun rouge, soluble à chaud dans HCl n et dans la pyridine, insoluble dans le chloroforme.
b) bis (3,4-dihydroxycinnamate) de pipérazine (dicaféate de pipérazine) ou PC 62-15.
Introduire 9 g d'acide caféique dans 90 ml d'alcool absolu. A la suspension obtenue ajouter rapidement et en agitant une solution de 4,85 g d'hexahydrate de pipérazine dans 10 ml d'alcool. L'acide caféique dispa raît, puis le dicaféate commence à précipiter. Essorer et laver à l'alcool. On obtient 11 g de produit sec. PF 204-2050 C (décomposition). Assez soluble dans l'eau.
Soluble dans SO4H2 n à chaud, dans OHNa n à froid en donnant une solution jaune-verdâtre virant ensuite au brun rouge, soluble dans la pyridine à chaud, insoluble dans le benzène.
Ces produits employés comme médicaments ont notamment une action sédative, tranquillisante, hypothermisante, antihypertensive et ils sont indiqués dans le traitement entre autres de l'excitation aiguë, de l'hyperthermie d'origine centrale, de l'hypertension, des oedèmes.
Process for the preparation of hydroxycinnamic acid derivatives
The present invention relates to a process for the preparation of medicaments which have the property of inhibiting enzymes which cause the decarboxylation of 3,4-dihydroxyphenylalanine (L. Dopa) and 5-hydroxytryptophan.
They are derivatives of hydroxy-cinnamic acid having the following formulas:
EMI1.1
in which:
R, is: CssHSN (pyridine) or
C5H11N (piperidine) or
C4HgNO (morpholine),
and R2 is: C4HtoN2 (piperazine).
The process according to the invention for the preparation of these compounds is characterized in that caffeic acid is dissolved or suspended in a solvent, in that then added in an equimolecular amount relative to the caffeic acid of pyridine, piperidine, piperazine or morpholine in solution in the same solvent as that in which the caffeic acid has been dissolved or suspended, and in that the material is collected, washed, drained and dried. precipitate formed.
If the solvent is acetone, hot caffeic acid is dissolved in this solvent and a compound of formula 1 is obtained.
If the solvent is absolute alcohol, the caffeic acid is suspended in the cold in this solvent and a compound of formula 2 is obtained.
The mode of preparation of the following compounds will be described more particularly:
Piperidine 1 / 3,4-dihydroxycinnamate (or piperidine caffeate)
C14H10O4N (referred to as PC 63-1)
EMI1.2
2 / bis (3,4-dihydroxycinnamate) piperazine (or piperazine dicafeate) C22H26O8N2 (referred to as PC 62-15)
EMI1.3
Preparation processes and characteristics
physicochemical
a) Piperidine 3,4-dihydroxycinnamate (piperidine caffeate) or PC 63-1.
Dissolve 9 g of caffeic acid in 320 ml of hot acetone and filter. To the solution thus obtained, cooled and stirred, the piperidine dilution (24.6 ml of piperidine and 15 ml of acetone) is added dropwise.
I1 then forms a viscous product which does not take long to solidify by trituration using a glass stirrer.
The precipitate obtained is filtered, washed with 4 times 10 ml of acetone and then dried under sulfuric vacuum.
A yellowish powder is thus obtained, with a melting point (mp) 1060 C, very soluble in water, slightly soluble in absolute alcohol, soluble in 95 alcohol, soluble in cold NaOH n, giving a yellow solution. greenish then turning to red brown, soluble in hot in HCl n and in pyridine, insoluble in chloroform.
b) piperazine bis (3,4-dihydroxycinnamate) (piperazine dicafeate) or PC 62-15.
Introduce 9 g of caffeic acid in 90 ml of absolute alcohol. To the suspension obtained add rapidly and with stirring a solution of 4.85 g of piperazine hexahydrate in 10 ml of alcohol. The caffeic acid disappears, then the dicafeate begins to precipitate. Wring out and wash with alcohol. 11 g of dry product are obtained. PF 204-2050 C (decomposition). Fairly soluble in water.
Soluble in SO4H2 n when hot, in OHNa n when cold, giving a yellow-greenish solution then turning to red brown, soluble in pyridine when hot, insoluble in benzene.
These products used as medicaments have in particular a sedative, tranquilizing, hypothermic and antihypertensive action and they are indicated in the treatment, inter alia, of acute excitement, hyperthermia of central origin, hypertension and edema.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR941566A FR3693M (en) | 1963-07-16 | 1963-07-16 | Hydroxy-cinnamic acid derivatives as drugs that inhibit l. dopa and 5 hydroxytryptophan decarboxylases. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH438271A true CH438271A (en) | 1967-06-30 |
Family
ID=8808388
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH817264A CH438271A (en) | 1963-07-16 | 1964-06-23 | Process for the preparation of hydroxycinnamic acid derivatives |
Country Status (4)
| Country | Link |
|---|---|
| BE (1) | BE649681A (en) |
| CH (1) | CH438271A (en) |
| FR (1) | FR3693M (en) |
| NL (1) | NL150681B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20031326A1 (en) * | 2003-06-27 | 2004-12-28 | Univ Degli Studi Milano | SALTS OF HYDROXYCINNAMIC ACIDS AND OPTICALLY ACTIVE HYDROXYSTYLBENES. |
-
1963
- 1963-07-16 FR FR941566A patent/FR3693M/en not_active Expired
-
1964
- 1964-06-23 CH CH817264A patent/CH438271A/en unknown
- 1964-06-24 BE BE649681A patent/BE649681A/xx unknown
- 1964-07-15 NL NL646408050A patent/NL150681B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR3693M (en) | 1965-11-22 |
| NL6408050A (en) | 1965-01-18 |
| NL150681B (en) | 1976-09-15 |
| BE649681A (en) | 1964-10-16 |
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