GB2162187A - New derivatives of 11-deoxo-glycyrrhetinic acid - Google Patents
New derivatives of 11-deoxo-glycyrrhetinic acid Download PDFInfo
- Publication number
- GB2162187A GB2162187A GB08518332A GB8518332A GB2162187A GB 2162187 A GB2162187 A GB 2162187A GB 08518332 A GB08518332 A GB 08518332A GB 8518332 A GB8518332 A GB 8518332A GB 2162187 A GB2162187 A GB 2162187A
- Authority
- GB
- United Kingdom
- Prior art keywords
- desoxo
- carboxylic acid
- esterified
- free
- salified
- 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
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Deoxoglycyrrhetinic acid derivatives of formula (I) have antiviral activity:- <IMAGE> wherein -COOR1 and -COOR2, which can be the same or different, are free, salified or esterified carboxylic acid groups.
Description
SPECIFICATION
New derivatives of 11-desoxo-glycyrrhetinic acid
The present invention is concerned with new derivatives of 11-desoxo-glycyrrhetinic acid, with the preparation thereof and with pharmaceutical compositions containing them.
The new derivatives of 11-desoxo-glycyrrhetinic acid according to the present invention are compounds of the general formula:
wherein -COOR, and -COOR2, which can be the same or different, are free, salified or esterified carboxylic groups.
Insofar as -COOR, and -COOR2 are esterified carboxylic acid groups, R, and R2 are preferably aliphatic hydrocarbon radicals containing up to 6 carbon atoms, which can be straight-chained or branched, saturated or unsaturated and unsubstituted or substituted.
The salts of the compounds of general formula (I) are preferably the alkali metal or alkaiine earth metal salts or the salts with non-toxic organic bases.
The compounds of general formula (I) can be prepared by reacting an ll-desoxo-glycyrrhetinic acid derivative of the general formula:
wherein -COOR; is a free or esterified carboxylic acid group, with a cyclohexene-carboxylic acid or with a reactive derivative thereof, for example an acid halide or an hydroxide thereof, a tetrahydrophthalic acid anhydride being preferred, whereafter, if desired, the product obtained is salified or esterified.
The reaction can be carried out in an inert solvent, pyridine being preferred.
For the preparation of salts of compounds (I) in which R, and/or R2 is a hydrogen atom, the free acid compound is reacted in known manner with an appropriate inorganic or organic basic compound, for example a basic alkali metal or alkaline earth metal compound, sodium hydroxide being preferred, or a non-toxic organic amine, for example a mono-, di-or trialkylamine or a mono-, di-or trialkanolamine. This reaction is preferably carried out in the presence of an inert solvent in which the salt is insoluble or only sparingly soluble.
If desired, free carboxylic acid groups present in the products obtained can be esterified in known manner, preferably by reaction with an appropriate diazoalkane or by reaction with an appropriate alcohol in the presence of sulphuric acid.
The new compounds according to the present invention possess valuable pharmaceutical properties, such as a good anti-viral activity. Consequently, the present invention also provides pharmaceutical compositions containing at least one of the new compounds, in admixture with a solid or liquid pharmaceutical diluent or carrier.
The following Example is given for the purpose of illustrating the present invention:
Example.
Mono-(l 1-desoxo- 18ss-glycyrrhet-3-yl)-cis- 1,2,3, 6-tetrahydrophthalate.
A mixture of 10 g. ll-desoxo-l 8P-glycyrrhetinic acid, 4.3 g. cis-1,2,3,6-tetrahydrophthalic anhydride and 13.3 ml. anhydrous pyridine was heated under reflux for 7 hours, whereafter thin later chromatography (n-butanol/"880" ammonia; 5:1 v/v) indicated that the reaction was complete. The reaction mixture was allowed to cool and then diluted with 125 ml. acetone. A solution of 15 ml. concentrated hydrochloric acid in 40 ml. distilled water was then added and the precipitated solid was filtered off, washed with a little 70% aqueous acetone and then thoroughly with distilled water. The resultant solid was dried to constant weight in a vacuum at 1100C. to give 12.65 g. of mono- (11-desoxo-18p-glycyrrhet-3-yl)-cis-1 2,3,6-tetrahydro-phthalate.Thin layer chromatographyy (n-butanolP'880" ammonia; 5:1 v/v) showed the product to have a degree of purity of at least 99%. The product had a melting point of 294-296"C. The infra-red absorption spectrum had major bands at via,, = 3300-2500 (COOH) and 1720-1710 (acids + ester). The NMR spectrum supported the expected structure.
12 g. of the diacid were slurried with 50 ml. acetone and 78.7 ml. 0.5M aqueous sodium hydroxide solution were added gradually thereto, using a Pasteur pipette. The resultant thick mixture was stirred manually. After all the base solution had been added, the mixture was warmed on a water bath. The resultant solution was filtered and poured, while stirring,- into 600 ml. acetone. The precipitated product was filtered off, washed with 95% aqueous acetone and then with pure acetone. The solid was dried to constant weight in a vacuum at 110 C. to give 10.67 g. of the disodium salt of mono-(11-desoxo-18p- glycyrrhet-3-yl)-cis-1 ,2,3,6-tetrahydrophthalate.
Thin layer chromatography (n-butanolr'880" ammonia; 5:1 v/v) indicated that the product had a degree of purity of at least 99%. The product had a melting point of > 360 C. The infra-red absorption spectrum showed major bands at vmax = 1715 (ester) and 1570-1590 (broad, COONa).
The corresponding dimethyl ester was prepared by reacting mono-(11-desoxo-18ss-glycyrrhet-3-yl)-cis- 1,2,3,6-tetrahydrophthalate with diazomethane; m.p. 196 -198 c.
The NMR spectrum (CDCI3) had signals at 5 = 5.68 (2 proton singlet, cyclohexene protons), 5.27 (1 proton singlet, C-12 proton), 4.56 (1 proton triplet, J = 7 Hz, C-3 proton), 3.70 (6 proton singlet, 2 methyl ester groupings) which supported the expected structure.
The corresponding dihexyl ester was prepared by converting mono-(l l-desoxo-18P-glycyrrhet-3-yl)-cis- 1,2,3,6-tetrahydrophthalate into the corresponding diacid chloride and reacting this with hexan-1-ol. The dihexyl ester was obtained in the form of a gum. The NMR spectrum (CDCI3) had signals at 5 = 5.61(2 proton singlet, cyclohexene protons); 5.20 (1 proton singlet, C-12 proton); 4.47 (1 proton, J = 8 Hz C-3 proton); 4.01 (4 proton triplet, J = 7 Hz CH2(CH2)4CH 3) which supported the expected structure.
Claims (6)
1. 11-Desoxo-glycyrrhetinic acid derivatives of the general formula:
wherein -COOR1 and -COOR2, which can be the same or different, are free salified or esterified carboxylic acid groups.
2. Mono-(ll-desoxo-l 8P-glycyrrhetS-yl )-cis-1,2,3,6- tetrahydrophthalate, the disodium salt thereof and the dimethyl and dihexyl esters thereof.
3. Process for the preparation of compounds according to claim 1, wherein an 11-desoxo-glycyrrhe- tinic acid derivative of the general formula:
in which -COORt is a free or esterified carboxylic acid group, is reacted with a cyclohexene-carboxylic acid or with a reactive derivative thereof, whereafter, if desired, the product obtained is salified or esterified.
4. Process according to claim 3 for the preparation of compounds according to claim 1, substantially as hereinbefore described and exemplified.
5. Compounds according to claim 1, whenever prepared by the process according to claim 3 or 4.
6. Pharmaceutical compositions containing at least one compound according to claim 1, in admixture with a solid or liquid pharmaceutical diluent or carrier.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848418981A GB8418981D0 (en) | 1984-07-25 | 1984-07-25 | Glycyrrhetinic acid |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8518332D0 GB8518332D0 (en) | 1985-08-29 |
| GB2162187A true GB2162187A (en) | 1986-01-29 |
| GB2162187B GB2162187B (en) | 1987-10-28 |
Family
ID=10564441
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB848418981A Pending GB8418981D0 (en) | 1984-07-25 | 1984-07-25 | Glycyrrhetinic acid |
| GB08518332A Expired GB2162187B (en) | 1984-07-25 | 1985-07-19 | New derivatives of 11-deoxo-glycyrrhetinic acid |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB848418981A Pending GB8418981D0 (en) | 1984-07-25 | 1984-07-25 | Glycyrrhetinic acid |
Country Status (1)
| Country | Link |
|---|---|
| GB (2) | GB8418981D0 (en) |
-
1984
- 1984-07-25 GB GB848418981A patent/GB8418981D0/en active Pending
-
1985
- 1985-07-19 GB GB08518332A patent/GB2162187B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2162187B (en) | 1987-10-28 |
| GB8518332D0 (en) | 1985-08-29 |
| GB8418981D0 (en) | 1984-08-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |