GB2140007A - 1,8-dihydroxy-10-acyl-9-anthrones - Google Patents
1,8-dihydroxy-10-acyl-9-anthrones Download PDFInfo
- Publication number
- GB2140007A GB2140007A GB08408666A GB8408666A GB2140007A GB 2140007 A GB2140007 A GB 2140007A GB 08408666 A GB08408666 A GB 08408666A GB 8408666 A GB8408666 A GB 8408666A GB 2140007 A GB2140007 A GB 2140007A
- Authority
- GB
- United Kingdom
- Prior art keywords
- dihydroxy
- anthrone
- acyl
- formula
- acid chloride
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
- C07C49/723—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic
- C07C49/727—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
- C07C49/737—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system having three rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
- C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a method for the preparation of 1,8-dihydroxy-10-acyl-9-anthrones, especially for use in the treatment of psoriasis, having the formula: <IMAGE> where R is an alkyl group having 2-4 carbon atoms, by using as the initial material, 1,8-dihydroxy-9-anthrone and an acid chloride having the formula RCOC2, where R represents the same as above. In accordance with the invention, harmful benzene is replaced with, for example toluene; this replacing is possible because pyridine is replaced with 2,6-dimethyl pyridine.
Description
SPECIFICATION
Method for the preparation of 1,8-dihydroxy-10-acyl-9-anthrones The present invention relates to a method for the preparation of i,8-dihydroxy-10-acyl-9-anthrones.
1,8-dihydroxy-9-anthrones substituted in the 10-position have been used for a few years to replace dithranol, which has been known since 1916 and used for the treatment of psoriasis, and which strongly stains the skin and clothing and strongly inflames the skin.
The structural formula of 1,8-di 1 ,8-dihydroxy-1 0-acyl-9-anthrones is as follows:
where R is an alkyl group having 2-4 carbon atoms. The compounds have been prepared according to
Finnish Patent Fl 57743 by causing anthraline to react in boiling benzene with an acid chloride, pyridine also being present. The acid chloride is used in an excess of 20%. The reaction mixture is boiled using return condensation for 10 hours, and the product is crystallized out from acetic acid. The yield in the method in question is, for example, only 25.5% of the theoretical.
The present invention provides a method for the preparation of 1,8-dihydroxy-10-acyl-9-anthrone having the formula:
where R is an alkyl group having 2-4 carbon atoms, by 1,8-dihydroxy-9-anthrone having the formula:
with an acid chloride having the formula RCOCI, where R represents the same as above, wherein the reaction is carried out in the presence of 2,6-dimethyl pyridine.
Using the process of the present invention it is possible to gain considerable advantages. The reaction temperature can be decreased to a level as low as -10 C, and in any case it is possible to use very low
reaction temperatures, for example room temperature. In addition, it is possible to avoid using benzene, which is strongly carcinogenic, and to use, for example, toluene, which is less harmful. Furthermore, the yield can be increased to 2-to 3-fold as compared with the method of Finnish Patent Fl 57743.
The invention is based on the observation that the replacement of pyridine with 2,6-dimethyl pyridine
makes it possible to lower the reaction temperature, to use toluene, xylene or chlorinated hydrocarbons such as dichloromethane ortetrachloroethene instead of benzene, and even to triple the yield as compared with the known method. If, furthermore, the acid chloride is used in an excess of 100%, the reaction can be completed in two hours.
From the above-mentioned low reaction temperature, which can be for example -1 0 C, to +20 C, it follows that the amount of impurities passing into the completed 1,8-dihydroxy-10-acyl-9-anthrone is small.
Thus the purification is a simple procedure compared with the respective procedure in the known method.
Acetonitrile or 2-propanol are suitable for use as the recrystallization solvent along with or instead of acetic acid.
The compounds prepared in accordance with the invention can be used in, for example, vaseline(R.T.M) or paraffin-based skin creams in concentrations of 0.5-5%, in sticks intended for skin care in concentrations of, for example, 2-8%, and in gels and in filmforming solutions.
The following examples illustrate the invention in greater detail.
Example 1
Butyryl chloride in an amount of 207 ml (213 g, 2.0 mol) was added in the course of 2 hours at a temperature below 0 C to a mixture which contained 2500 ml toluene, 226 g (1.0 mol) 1,8-dihydroxy-9-anthrone and 232 ml (214 g, 2.0 mol) 2,6-dimethyl pyridine.
The mixture was stirred at a temperature below O"C for a further two hours after the addition.
The mixture was thereafter heated to +40 C, the hydrochloride of the 2,6-dimethyl pyridine was filtered off, and most of the toluene was evaporated at lowered pressure. 2300 ml isopropanol was added to the residue, the mixture was cooled to - 10 C, and the precipitate was recovered by filtration. Recrystallization was carried out from acetonitrile, whereby a yield of 222 g 1 ,8-dihydroxy-1 0-butyryl-9-anthrone was obtained. This was 75% of the theoretical.
Example 2
The procedure was fully analogous to that in Example 1, except that xylene was used instead oftoluene.
The yield was the same as in Example 1, i.e.75%.
Example 3
Propionyl chloride in an amount of 86.9 ml (92.5 g, 1 mole) was added in the course of about 2 hours at a temperature below 0 C to a mixture which contained 1200 mltoluene, 113 g (0.5 mol) 1 ,8-dihydroxy-9-anthrone and 116 ml (107 g, 1 mol) 2,6-dimethyl pyridine. Stirring was continued for a further two hours after the addition.
The 1 ,8-dihydroxy-1 0-propionyl-9-anthrone obtained as the result was separated by the procedure presented in Example 1.The yield was (120g) 82% of the theoretical.
Example 4
Starting from 1,8-dihydroxy-9-anthrone and valeryl chloride and using valeryl chloride in an excess of 100% and by proceeding otherwise as in Example 1, 1 ,8-dihydroxy-1 0-valeryl-9-anthrone was obtained as the result, the yield being 53%.
Example 5
Pharmaceutical compositions were prepared by using the following consitituents and amounts:
liquid paraffin 40-60%
solid paraffin 40-60%
microcrystalline wax 0.5-5%
In addition, about 2-8% 1,8-dihydroxy-10-butyryl-9-anthrone was mixed with the carrier composition presented above. Sticks intended for skin care were molded from the mixture, and it was observed that the use properties of the sticks were good and, furthermore, the medication in the sticks remained unchanged, specifically unoxidized.
Claims (7)
1. A method for the preparation of 1 ,8-dihydroxy-1 0-acyl-9-anthrone, having the formula:
where R is an alkyl group having 2-4 carbon atoms, by 1,8-dihydroxy-9-anthrone having the formula:
with an acid chloride having the formula RCOCI, where R represents the same as above, wherein the reaction is carried out in the presence of 2,6-dimethyl pyridine.
2. A method according to Claim 1, wherein the reaction is carried out in a solvent selected from toluene, xylene and chlorinated hydrocarbons.
3. A method according to Claim 2 wherein said solvent is dichloromethane or tetrachloroethane.
4. A method according to any preceding claim wherein the acid chloride is used in an excess of 100%.
5. A method according to any preceding claim wherein the reaction temperature is -10 to +200C, the acid chloride is added in the course of two hours, and stirring is continued for a further two hours.
6. A method according to Claim 1 substantially as herein described with reference to any one of the
Examples.
7. A pharmaceutical composition comprising: 1,8-dihydroxy-10-acyl-9-anthrone 2-8%,
liquid paraffin 40-60%,
solid paraffin 40-60% .and microcrystalline wax 0.5-5%.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI831739A FI66585C (en) | 1983-05-18 | 1983-05-18 | FOERFARANDE FOER FRAMSTAELLNING AV SAERSKILT VID BEHANDLING AVSORIASIS ANVAENDBARA 1,8-DIHYDROXI-10-ACYL-9-ANTRONER |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8408666D0 GB8408666D0 (en) | 1984-05-16 |
| GB2140007A true GB2140007A (en) | 1984-11-21 |
| GB2140007B GB2140007B (en) | 1986-04-09 |
Family
ID=8517222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08408666A Expired GB2140007B (en) | 1983-05-18 | 1984-04-04 | 1,8-dihydroxy-10-acyl-9-anthrones |
Country Status (31)
| Country | Link |
|---|---|
| JP (1) | JPS59212443A (en) |
| KR (1) | KR840009059A (en) |
| AU (1) | AU560079B2 (en) |
| BE (1) | BE899334A (en) |
| CA (1) | CA1212943A (en) |
| CH (1) | CH659464A5 (en) |
| CS (1) | CS256379B2 (en) |
| DD (1) | DD223702A5 (en) |
| DE (1) | DE3418382A1 (en) |
| DK (1) | DK154207C (en) |
| ES (1) | ES8505167A1 (en) |
| FI (1) | FI66585C (en) |
| FR (1) | FR2546162B1 (en) |
| GB (1) | GB2140007B (en) |
| GR (1) | GR79971B (en) |
| HU (1) | HUT36076A (en) |
| IL (1) | IL71446A (en) |
| IN (1) | IN156115B (en) |
| IS (1) | IS2902A7 (en) |
| IT (1) | IT1173473B (en) |
| LU (1) | LU85292A1 (en) |
| NL (1) | NL8401074A (en) |
| NO (1) | NO157099C (en) |
| NZ (1) | NZ207592A (en) |
| PH (1) | PH20038A (en) |
| PL (1) | PL141866B1 (en) |
| PT (1) | PT78603B (en) |
| SE (1) | SE453827B (en) |
| SU (1) | SU1240351A3 (en) |
| YU (1) | YU81784A (en) |
| ZA (1) | ZA842223B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2580631A1 (en) * | 1985-04-17 | 1986-10-24 | Cird | HYDROXY-1 ACYLOXY-8 ACYL-10 ANTHRONES, PROCESS FOR THEIR PREPARATION AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
| FR2591222A1 (en) * | 1985-12-11 | 1987-06-12 | Cird | 1,8-DIHYDROXY-1,8-PHENYL-10-ANTHRONE-9 OR ANTHRANOL-9 MONO, DI AND TRI-ESTERS, PROCESS FOR THEIR PREPARATION AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
| US4696941A (en) * | 1984-06-29 | 1987-09-29 | Groupement d'Interet Economique dit: Centre International 'de Recherches Dermatologiques C.I.R.D. | 1,8-diacyloxy-10-acylanthrones |
| US4826996A (en) * | 1980-10-21 | 1989-05-02 | Groupement D'interet Economique Dit Centre International De Recherches Dermatologioues C.I.R.D. | 1,8,-dihydroxy-9-anthrones substituted in the 10-position |
| US4843097A (en) * | 1984-06-13 | 1989-06-27 | Groupement D'interet Economique Dit: Centre International De Recherches Dermatologiques C.I.R.D. | 10-aryl-1,8-dihydroxy-9-anthrones and their esters, process for preparing same, and use of same in human and veterinary medicine and in cosmetics |
| DE4231636A1 (en) * | 1992-09-22 | 1994-03-24 | Beiersdorf Ag | New anthrone and anthracene derivatives substituted in the 10-position, processes for their preparation, pharmaceutical or cosmetic compositions containing these compounds and their use |
| WO1995003266A1 (en) * | 1993-07-19 | 1995-02-02 | Teva Pharmaceutical Industries, Ltd. | 10-substituted 1,8-dihydroxy-9(10h) anthracenone pharmaceuticals |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69223723T2 (en) * | 1991-10-04 | 1998-04-16 | Fisher & Paykel | humidifier |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI57743C (en) * | 1979-03-29 | 1980-10-10 | Orion Yhtymae Oy | FREQUENCY REQUIREMENT FOR NYA 1,8-DIHYDROXI-10-ACYL-9-ANTRONER MOT PSORIASIS |
-
1983
- 1983-05-18 FI FI831739A patent/FI66585C/en not_active IP Right Cessation
-
1984
- 1984-03-22 AU AU25998/84A patent/AU560079B2/en not_active Ceased
- 1984-03-22 NZ NZ207592A patent/NZ207592A/en unknown
- 1984-03-23 IT IT20213/84A patent/IT1173473B/en active
- 1984-03-26 ZA ZA842223A patent/ZA842223B/en unknown
- 1984-03-29 IN IN209/CAL/84A patent/IN156115B/en unknown
- 1984-03-30 DK DK173584A patent/DK154207C/en active IP Right Grant
- 1984-04-04 GB GB08408666A patent/GB2140007B/en not_active Expired
- 1984-04-04 NL NL8401074A patent/NL8401074A/en not_active Application Discontinuation
- 1984-04-05 BE BE0/212698A patent/BE899334A/en not_active IP Right Cessation
- 1984-04-05 IL IL71446A patent/IL71446A/en not_active IP Right Cessation
- 1984-04-05 GR GR74318A patent/GR79971B/el unknown
- 1984-04-05 IS IS2902A patent/IS2902A7/en unknown
- 1984-04-06 LU LU85292A patent/LU85292A1/en unknown
- 1984-04-18 ES ES531760A patent/ES8505167A1/en not_active Expired
- 1984-04-18 CS CS842911A patent/CS256379B2/en unknown
- 1984-04-27 KR KR1019840002278A patent/KR840009059A/en not_active Application Discontinuation
- 1984-05-02 FR FR8406790A patent/FR2546162B1/en not_active Expired
- 1984-05-04 JP JP59090047A patent/JPS59212443A/en active Pending
- 1984-05-08 SU SU843735603A patent/SU1240351A3/en active
- 1984-05-10 YU YU00817/84A patent/YU81784A/en unknown
- 1984-05-16 SE SE8402649A patent/SE453827B/en not_active IP Right Cessation
- 1984-05-16 PH PH30686A patent/PH20038A/en unknown
- 1984-05-16 NO NO841965A patent/NO157099C/en unknown
- 1984-05-17 CA CA000454593A patent/CA1212943A/en not_active Expired
- 1984-05-17 PL PL1984247724A patent/PL141866B1/en unknown
- 1984-05-17 CH CH2431/84A patent/CH659464A5/en not_active IP Right Cessation
- 1984-05-17 PT PT78603A patent/PT78603B/en unknown
- 1984-05-17 HU HU841908A patent/HUT36076A/en unknown
- 1984-05-17 DE DE19843418382 patent/DE3418382A1/en not_active Withdrawn
- 1984-05-17 DD DD84263131A patent/DD223702A5/en unknown
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4826996A (en) * | 1980-10-21 | 1989-05-02 | Groupement D'interet Economique Dit Centre International De Recherches Dermatologioues C.I.R.D. | 1,8,-dihydroxy-9-anthrones substituted in the 10-position |
| US4843097A (en) * | 1984-06-13 | 1989-06-27 | Groupement D'interet Economique Dit: Centre International De Recherches Dermatologiques C.I.R.D. | 10-aryl-1,8-dihydroxy-9-anthrones and their esters, process for preparing same, and use of same in human and veterinary medicine and in cosmetics |
| US4696941A (en) * | 1984-06-29 | 1987-09-29 | Groupement d'Interet Economique dit: Centre International 'de Recherches Dermatologiques C.I.R.D. | 1,8-diacyloxy-10-acylanthrones |
| FR2580631A1 (en) * | 1985-04-17 | 1986-10-24 | Cird | HYDROXY-1 ACYLOXY-8 ACYL-10 ANTHRONES, PROCESS FOR THEIR PREPARATION AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
| US4755530A (en) * | 1985-04-17 | 1988-07-05 | Centre International De Recherches Dermatologiques (C.I.R.D) | 1-hydroxy-8-acyloxy-10-acyl anthrones, process for their preparation and their use in human or veterinary medicines and in cosmetic formulations |
| FR2591222A1 (en) * | 1985-12-11 | 1987-06-12 | Cird | 1,8-DIHYDROXY-1,8-PHENYL-10-ANTHRONE-9 OR ANTHRANOL-9 MONO, DI AND TRI-ESTERS, PROCESS FOR THEIR PREPARATION AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
| DE4231636A1 (en) * | 1992-09-22 | 1994-03-24 | Beiersdorf Ag | New anthrone and anthracene derivatives substituted in the 10-position, processes for their preparation, pharmaceutical or cosmetic compositions containing these compounds and their use |
| WO1995003266A1 (en) * | 1993-07-19 | 1995-02-02 | Teva Pharmaceutical Industries, Ltd. | 10-substituted 1,8-dihydroxy-9(10h) anthracenone pharmaceuticals |
| US5426197A (en) * | 1993-07-19 | 1995-06-20 | Teva Pharmaceutical Industries, Ltd. | 10-substituted 1,8-dihydroxy-9(10H) anthracenone pharmaceuticals |
| US5661187A (en) * | 1993-07-19 | 1997-08-26 | Teva Pharmaceutical Industries, Ltd. | 10-substituted 1,8-dihydroxy-9 (10H) anthracenone pharmaceuticals |
| US5844004A (en) * | 1993-07-19 | 1998-12-01 | Teva Pharmaceutical Industries, Ltd. | 10-substituted 1,8-dihydroxy-9 (10H) anthracenone pharmaceuticals |
| US6127426A (en) * | 1993-07-19 | 2000-10-03 | Teva Pharmaceutical Industries Ltd. | 10-substituted 1,8-dihydroxy-9 (10H) anthracenone pharmaceuticals |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |