IT9021768A1 - Derivato della melatonina ad attivita' terapeutica in dermatologia. - Google Patents
Derivato della melatonina ad attivita' terapeutica in dermatologia. Download PDFInfo
- Publication number
- IT9021768A1 IT9021768A1 IT021768A IT2176890A IT9021768A1 IT 9021768 A1 IT9021768 A1 IT 9021768A1 IT 021768 A IT021768 A IT 021768A IT 2176890 A IT2176890 A IT 2176890A IT 9021768 A1 IT9021768 A1 IT 9021768A1
- Authority
- IT
- Italy
- Prior art keywords
- melatonin
- dermatology
- derived
- compound
- therapeutic activity
- Prior art date
Links
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 title claims description 6
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 title claims description 5
- 229960003987 melatonin Drugs 0.000 title claims description 5
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 3
- LKBZJSNJPQMODB-UHFFFAOYSA-N n-[2-(5-methoxy-1h-indol-3-yl)ethyl]undec-10-enamide Chemical compound COC1=CC=C2NC=C(CCNC(=O)CCCCCCCCC=C)C2=C1 LKBZJSNJPQMODB-UHFFFAOYSA-N 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 5
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 claims description 4
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 229960002703 undecylenic acid Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 206010017533 Fungal infection Diseases 0.000 claims 1
- 208000031888 Mycoses Diseases 0.000 claims 1
- 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- -1 10-undecenoyl Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 210000003737 chromaffin cell Anatomy 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 210000002745 epiphysis Anatomy 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- MZFGYVZYLMNXGL-UHFFFAOYSA-N undec-10-enoyl chloride Chemical compound ClC(=O)CCCCCCCCC=C MZFGYVZYLMNXGL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
- A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Description
Descrizione dell'invenzione industriale avente per titolo: "DERIVATO DELLA MELATONINA AD ATTIVITÀ' TERAPEUTICA IN DERMATOLOGIA"
La presente invenzione ha per oggetto la 5-metossi-N- {10-undecenoil )triptamina di formula:
un procedimento per la sua preparazione e composizioni farmaceutiche die lo contengalo.
La melatonina è un ormone sintetizzato a livello dell'epifisi, della retina e, presnnibilmente, a livello delle cellule cromaffini del tratto intestinale, la cui biosintesi, che segue un ritmo circadiano, culmina durante le ore notturne.
Il carpaste dell' invenzione, di seguito indicato per brevità con la sigla PU-2049, è il risultato dell'unione di due sostanze farmacologicamente attive: la melatonina, già nota per la sua azione nel trattamento topico della psoriasi (come descritto nella domanda di brevetto WG 87/00432), e l'acido 10-undecenoico, che ha dimostrato buona attività antimicrobica, e, particolarmente, antimicotica.
Si e ora trovato che il PU-2049 ha dimostrato una maggiore biodisponibilità per la somministrazione topica. Pertanto l'invenzione ha per oggetto l'uso del PU-2049 carie agente terapeutico in formulazioni previste oon tecniche ed eccipienti convenzionali, quali quelli descritti in "Rendngton's Pharmaceutical Sciences Handbook" Mack Pub. Co., NY, USA.
Le corposizioni farmaceutiche dell'invenzione conterranno da 1 a 500 mg di PU-2049 e saranno scnministrate in una o più applicazioni al giorno, a seconda dell'entità del sintero.
Esempi di tali composizioni comrendono creme, pomate, oli unguenti, e ogni altra forma adatta per applicazioni topiche.
Il ccnposto dell'invenzione viene preparato a partire dalla melatonina per reazione con acido 10-undecenoico o, più preferibilmente, con un derivato attivato (cloruro acilico, anidride, imidazolide, e simili) di acido 10-undecenoico.
L'impiego di cloruro acilioo prevede la presenza di accettori di acidità (piridina, ammine terziarie, carbonati o bicarbonati di metalli alcalini o alcalino-terrosi) in solventi inerti.
Il seguente esempio illustra ulteriormente l'invenzione.
ESEMPIO
Ad una soluzione, mantenuta al buio, di 1,90 g di 5-metossitriptaraina (melatonina) (0,01 moli) in 50 mi di una miscela benzene/piridina 7/3 si aggiungerlo 2,13 mi di 10-undecenoil cloruro (0,01 moli). Si lascia sotto agitazione a temperatura antoiente per 1 ora, si evapora il solvente a pressione ridotta e si riprende con benzene.
Si lava la fase organica con H21 al 10%, con NaOH al 5%, infine con acqua. Si secca su solfato di sodio, si evapora il solvente a pressione ridotta e si stempera il residuo in esano/etere isopropilico, ottenendo 1,9 g di PU-2049.
Descrizione spettro NMR (CDCl3)
Descrizione spettro IR (Nujol)
Claims (5)
- RIVENDICAZION 1. 5-metossi-N-(10-undecenoil)-triptamina di formula (I)
- 2. Procedimento per la preparazione del composto della rivendicazione 1 caratterizzato dal fatto che si fa reagire melatonina con acido 10-undecenoico o oon un suo derivato attivo.
- 3. Il composto della rivendicazione 1 come agente terapeutico.
- 4. Corposizioni farmaceutiche contenenti il corposto dalla rivendicazione 1 cerne principio attivo in miscela ccn veicoli opportuni.
- 5. L'uso del conposto della rivendicazione 1 per la preparazione di un medicamento per la psoriasi e di forme di infezione micotica.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT02176890A IT1243846B (it) | 1990-10-17 | 1990-10-17 | Derivato della melatonina ad attivita' terapeutica in dermatologia. |
| DE69104054T DE69104054T2 (de) | 1990-10-17 | 1991-10-11 | Melatoninderivat mit therapeutischer aktivität, das in der dermatologie anwendbar ist. |
| ES91917801T ES2060405T3 (es) | 1990-10-17 | 1991-10-11 | Derivado de la melatonina que tiene actividad terapeutica en dermatologia. |
| EP91917801A EP0553155B1 (en) | 1990-10-17 | 1991-10-11 | Melatonin derivative having therapeutic activity in dermatology |
| AU87154/91A AU8715491A (en) | 1990-10-17 | 1991-10-11 | Melatonin derivative having therapeutic activity in dermatology |
| DK91917801.2T DK0553155T3 (da) | 1990-10-17 | 1991-10-11 | Melatoninderiviat med dermatologisk terapeutisk aktivitet |
| AT91917801T ATE111450T1 (de) | 1990-10-17 | 1991-10-11 | Melatoninderivat mit therapeutischer aktivität, das in der dermatologie anwendbar ist. |
| PCT/EP1991/001940 WO1992006955A1 (en) | 1990-10-17 | 1991-10-11 | Melatonin derivative having therapeutic activity in dermatology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT02176890A IT1243846B (it) | 1990-10-17 | 1990-10-17 | Derivato della melatonina ad attivita' terapeutica in dermatologia. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IT9021768A0 IT9021768A0 (it) | 1990-10-17 |
| IT9021768A1 true IT9021768A1 (it) | 1992-04-17 |
| IT1243846B IT1243846B (it) | 1994-06-28 |
Family
ID=11186595
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT02176890A IT1243846B (it) | 1990-10-17 | 1990-10-17 | Derivato della melatonina ad attivita' terapeutica in dermatologia. |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0553155B1 (it) |
| AT (1) | ATE111450T1 (it) |
| AU (1) | AU8715491A (it) |
| DE (1) | DE69104054T2 (it) |
| DK (1) | DK0553155T3 (it) |
| ES (1) | ES2060405T3 (it) |
| IT (1) | IT1243846B (it) |
| WO (1) | WO1992006955A1 (it) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2680366B1 (fr) * | 1991-08-13 | 1995-01-20 | Adir | Nouveaux derives d'arylethylamines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2741799B1 (fr) * | 1995-12-04 | 1998-01-02 | Oreal | Utilisation de melatonine dans une composition pour traiter les signes cutanes des etats de fatigue |
| FR2741802B1 (fr) * | 1995-12-04 | 1998-01-02 | Oreal | Utilisation de melatonine pour traiter les peaux sensibles |
| WO1998006695A1 (fr) * | 1996-08-09 | 1998-02-19 | Sederma S.A. | Derives de la melatonine et leur utilisation dans les compositions cosmetiques ou dermopharmaceutiques |
| FR2753095B1 (fr) * | 1996-09-06 | 1998-11-20 | Oreal | Utilisation de la melatonine comme agent anti-inflammatoire dans une composition cosmetique ou pharmaceutique |
| ES2209649B1 (es) * | 2002-12-09 | 2005-03-16 | Carlos Arana Molina (Titular Al 25%) | Utilizacion de la melatonina para la higiene bucodental para uso humano y veterinario como producto activo. |
| WO2005044261A1 (en) * | 2003-10-27 | 2005-05-19 | University Of Iowa Research Foundation | Melatonin analogue prodrugs |
| EP2282735B1 (en) | 2008-04-21 | 2019-01-16 | Signum Biosciences, Inc. | Pp2a modulators for treating alzheimer, parkinson, diabetes |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4746674A (en) * | 1985-08-27 | 1988-05-24 | Cellena (Cell Engineering) Ag | Melatonin compositions and uses thereof |
| GB8517958D0 (en) * | 1985-07-16 | 1985-08-21 | Cellena Cell Eng Ag | Compositions containing melatonin/homologues |
-
1990
- 1990-10-17 IT IT02176890A patent/IT1243846B/it active IP Right Grant
-
1991
- 1991-10-11 DE DE69104054T patent/DE69104054T2/de not_active Expired - Fee Related
- 1991-10-11 ES ES91917801T patent/ES2060405T3/es not_active Expired - Lifetime
- 1991-10-11 WO PCT/EP1991/001940 patent/WO1992006955A1/en active IP Right Grant
- 1991-10-11 EP EP91917801A patent/EP0553155B1/en not_active Expired - Lifetime
- 1991-10-11 AU AU87154/91A patent/AU8715491A/en not_active Abandoned
- 1991-10-11 DK DK91917801.2T patent/DK0553155T3/da active
- 1991-10-11 AT AT91917801T patent/ATE111450T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU8715491A (en) | 1992-05-20 |
| ATE111450T1 (de) | 1994-09-15 |
| EP0553155B1 (en) | 1994-09-14 |
| IT1243846B (it) | 1994-06-28 |
| DE69104054T2 (de) | 1995-02-02 |
| DE69104054D1 (de) | 1994-10-20 |
| DK0553155T3 (da) | 1995-03-20 |
| WO1992006955A1 (en) | 1992-04-30 |
| ES2060405T3 (es) | 1994-11-16 |
| EP0553155A1 (en) | 1993-08-04 |
| IT9021768A0 (it) | 1990-10-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 0001 | Granted | ||
| TA | Fee payment date (situation as of event date), data collected since 19931001 |
Effective date: 19941027 |