IT9021697A1 - Derivato di mentolo ad azione spasmolitica - Google Patents
Derivato di mentolo ad azione spasmolitica Download PDFInfo
- Publication number
- IT9021697A1 IT9021697A1 IT021697A IT2169790A IT9021697A1 IT 9021697 A1 IT9021697 A1 IT 9021697A1 IT 021697 A IT021697 A IT 021697A IT 2169790 A IT2169790 A IT 2169790A IT 9021697 A1 IT9021697 A1 IT 9021697A1
- Authority
- IT
- Italy
- Prior art keywords
- heptanoate
- action
- menthol
- spasmolithic
- menthyl
- Prior art date
Links
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 title claims 2
- 229940041616 menthol Drugs 0.000 title claims 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 title description 4
- 229940127291 Calcium channel antagonist Drugs 0.000 claims abstract description 3
- 239000000480 calcium channel blocker Substances 0.000 claims abstract description 3
- FCZWGCWNVXJYGP-UHFFFAOYSA-N (5-methyl-2-propan-2-ylcyclohexyl) heptanoate Chemical compound CCCCCCC(=O)OC1CC(C)CCC1C(C)C FCZWGCWNVXJYGP-UHFFFAOYSA-N 0.000 claims abstract 4
- 239000000812 cholinergic antagonist Substances 0.000 claims abstract 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 230000002048 spasmolytic effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 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
- 239000000203 mixture Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- 239000003610 charcoal Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VWIFECXIKIWAPI-UHFFFAOYSA-N (1-methyl-4-propan-2-ylcyclohexyl) heptanoate Chemical compound CCCCCCC(=O)OC1(C)CCC(C(C)C)CC1 VWIFECXIKIWAPI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- UCVODTZQZHMTPN-UHFFFAOYSA-N heptanoyl chloride Chemical compound CCCCCCC(Cl)=O UCVODTZQZHMTPN-UHFFFAOYSA-N 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 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
- 239000000829 suppository Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/013—Esters of alcohols having the esterified hydroxy group bound to a carbon atom of a ring other than a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Descrizione dell'invenzione industriale avente per titolo: "DERIVATO DI MENTOLO AD AZIONE SPASMOLITICA"
La presente invenzione ha per oggetto l'eptanoato di 1-mentile, di formula
un procedimento per la sua preparazione e composizicni farmaceutiche che lo contengono.
Il composto dell'invenzione, di seguito indicato per brevità anche con la sigla PO 2054, è risultato essere dotato di potente attività calcio-antagonista che si manifesta con un marcato effetto spasmolitico sia in vitro sia in vivo, soprattutto a livello dell'intestino, così da renderlo particolarmente adatto cane farmaco per il trattamento del colon irritabile. A tal fine, PU 2054, che ha anche rivelato una sorprendente efficacia e una lunga durata d'azione, è convenientemente formulato in ccnposizicni farmaceutiche atte alla sonministrazione orale, rettale o parenterale, ricorrendo a tecniche ed eccipienti convenzionali quali quelli descritti in "Remingtan's Pharmaceutical Sciences Hand- hook", Mack Pub.Co., NY, USA.
Le composizioni dell’invenzione conterranno da 1 a 500 mg di PU 2054 e saranno somministrate da 1 a 4 volte al giorno, a seconda delle condizioni del paziente. Eseirpi di tali composizioni comprendono capsule, compresse, confetti, forme a rilascio controllato, sciroppi, gocce, supposte, fiale o flaccecini iniettabili.
Il composto dell'invenzione viene preparato a partire da 1-mentolo per esterificazione con acido eptanoico o, più preferibilmente, con un derivato attivato (cloruro acilico, anidride, imidazolide e simili) di acido eptanoico.
Inpiegando il cloruro acilico, si opera preferibilmente in presenza di accettori di acidità (piridina, armine terziarie, carbonati o bicarbonati) in solventi anidri.
Il seguente esempio illustra ulteriormente l'invenzione.
ESEMPIO
Si sciolgono 3,12 g di 1-mentolo (0,02 noli) in 50 mi di una miscela benzene/piridina 7/3, quindi si aggiungono 3,87 mi di cloruro di eptanoile (3,71 g, 0,025 moli) e si lascia sotto agitazione a temperatura ambiente per 2 ore. Si elimina per filtrazione su buchner il cloruro di piridinio precipitato, si evapora il solvente a pressione ridotta e si riprende il residuo con etere etilico.
Si lava la fase organica con NaOH al 5%, con H31 al 10%, poi con acqua. Si secca su solfato di sodio, si evapora il solvente a pressione ridotta e si riprende con CCl4. Si aggiunge una spatolata di carbone decolorante, si riscalda all'ebollizione e si elimina il carbone per filtrazione a caldo su celite. Dopo evaporazione del solvente a pressione ridotta si ottengono 3,8 g di PU 2054.
Analisi elementare
Coefficiente di rotazione ottica
Descrizione spettro NMR (CDCl3)
Descrizione spettro IR (Nujol):
Claims (5)
- RIVENDICAZIONI 1. Eptanoato di mentile di formula
- 2. Eptanoato di mentile come agente terapeutico.
- 3. Procedimento per la preparazione di eptanoato di mentile caratterizzato dal fatto che si fa reagire mentolo con acido eptanoico o con un suo derivato attivo.
- 4. Composizioni farmaceutiche contenenti cane principio attivo eptanoato di mentile in miscela con veicoli opportuni.
- 5. Uso di eptanoato di mentile per la preparazione di un farmaco spasmolitico e calcio-antagonista.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT02169790A IT1243439B (it) | 1990-10-10 | 1990-10-10 | Derivato di mentolo ad azione spasmolitica |
| DK91917124.9T DK0552186T3 (da) | 1990-10-10 | 1991-10-02 | Methol-derivat med spasmolytisk aktivitet |
| EP91917124A EP0552186B1 (en) | 1990-10-10 | 1991-10-02 | Menthol derivative having spasmolytic activity |
| AT91917124T ATE116962T1 (de) | 1990-10-10 | 1991-10-02 | Mentholderivate mit spasmolytik aktivität. |
| PCT/EP1991/001881 WO1992006947A1 (en) | 1990-10-10 | 1991-10-02 | Menthol derivative having spasmolytic activity |
| DE69106720T DE69106720T2 (de) | 1990-10-10 | 1991-10-02 | Mentholderivate mit spasmolytik aktivität. |
| AU85482/91A AU8548291A (en) | 1990-10-10 | 1991-10-02 | Menthol derivative having spasmolytic activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT02169790A IT1243439B (it) | 1990-10-10 | 1990-10-10 | Derivato di mentolo ad azione spasmolitica |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IT9021697A0 IT9021697A0 (it) | 1990-10-10 |
| IT9021697A1 true IT9021697A1 (it) | 1992-04-10 |
| IT1243439B IT1243439B (it) | 1994-06-10 |
Family
ID=11185557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT02169790A IT1243439B (it) | 1990-10-10 | 1990-10-10 | Derivato di mentolo ad azione spasmolitica |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0552186B1 (it) |
| AT (1) | ATE116962T1 (it) |
| AU (1) | AU8548291A (it) |
| DE (1) | DE69106720T2 (it) |
| DK (1) | DK0552186T3 (it) |
| IT (1) | IT1243439B (it) |
| WO (1) | WO1992006947A1 (it) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100411205B1 (ko) | 2001-08-27 | 2003-12-18 | 주식회사 태평양 | 멘톨 유도체 및 그의 제조방법 |
| JP4459167B2 (ja) * | 2003-06-30 | 2010-04-28 | 日本製薬株式会社 | メントール含有平滑筋蠕動抑制剤 |
-
1990
- 1990-10-10 IT IT02169790A patent/IT1243439B/it active IP Right Grant
-
1991
- 1991-10-02 DK DK91917124.9T patent/DK0552186T3/da active
- 1991-10-02 WO PCT/EP1991/001881 patent/WO1992006947A1/en not_active Ceased
- 1991-10-02 AT AT91917124T patent/ATE116962T1/de not_active IP Right Cessation
- 1991-10-02 EP EP91917124A patent/EP0552186B1/en not_active Expired - Lifetime
- 1991-10-02 AU AU85482/91A patent/AU8548291A/en not_active Abandoned
- 1991-10-02 DE DE69106720T patent/DE69106720T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE69106720T2 (de) | 1995-07-20 |
| DE69106720D1 (de) | 1995-02-23 |
| AU8548291A (en) | 1992-05-20 |
| DK0552186T3 (da) | 1995-05-15 |
| IT1243439B (it) | 1994-06-10 |
| ATE116962T1 (de) | 1995-01-15 |
| IT9021697A0 (it) | 1990-10-10 |
| EP0552186A1 (en) | 1993-07-28 |
| WO1992006947A1 (en) | 1992-04-30 |
| EP0552186B1 (en) | 1995-01-11 |
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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: 19951027 |