CA1188616A - Pharmaceutical preparations - Google Patents
Pharmaceutical preparationsInfo
- Publication number
- CA1188616A CA1188616A CA000399814A CA399814A CA1188616A CA 1188616 A CA1188616 A CA 1188616A CA 000399814 A CA000399814 A CA 000399814A CA 399814 A CA399814 A CA 399814A CA 1188616 A CA1188616 A CA 1188616A
- Authority
- CA
- Canada
- Prior art keywords
- hydroxy
- hydrogen
- formula
- signifies
- beta
- 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.)
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Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
Abstract
Abstract Topically applicable pharmaceutical preparation, containing a D-homosteroid of the formula I
in which R6 signifies hydrogen, methyl, chlorine or fluorine, R9 signifies hydrogen, fluorine or chlorine, R11 sig-nifies oxo or (.alpha.-H,.beta.-OH), R17a signifies hydroxy or acyloxy, R20 signifies a group -O-R201 or -CH2 -R21, R201 signifies lower-alkyl, chloro-lower-alkyl or fluoro--lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy or acyloxy and the dotted 1,2-bond signifies an optional C-C bond, and, where R20 is a group -O-R201, a double bond can be present in the 16,17-position, and a compound of the formula II
in which R1 signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signify hydrogen, lower-alkoxy, hydroxy--lower-alkoxy or two adjacent symbols R1, R2, R3 and R4 together signify methylene-dioxy, and at least one symbol R1, R2, R3 or R4 contains oxygen.
in which R6 signifies hydrogen, methyl, chlorine or fluorine, R9 signifies hydrogen, fluorine or chlorine, R11 sig-nifies oxo or (.alpha.-H,.beta.-OH), R17a signifies hydroxy or acyloxy, R20 signifies a group -O-R201 or -CH2 -R21, R201 signifies lower-alkyl, chloro-lower-alkyl or fluoro--lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy or acyloxy and the dotted 1,2-bond signifies an optional C-C bond, and, where R20 is a group -O-R201, a double bond can be present in the 16,17-position, and a compound of the formula II
in which R1 signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signify hydrogen, lower-alkoxy, hydroxy--lower-alkoxy or two adjacent symbols R1, R2, R3 and R4 together signify methylene-dioxy, and at least one symbol R1, R2, R3 or R4 contains oxygen.
Description
til6 RA~? 4_51~
The present invention is concerned with topically applicable pharmaceutical preparations which have, in particular, antiinflammatory activity. The preparations in accordance with the invention contain as the active substances a D-homosteroid of the formula coR2c~
R1~Rl?a I
~6 in which R6 signified hydrogen, methyl, chlorine or fluorine, R signifies hydrogen, fluorine or chlorine, Rll signifies oxo or (~-H,~ OH), R 7a sig-nifies hydroxy or acyloxy, R20 signifies a group O-R20l or -CH _R21 R201 nifies lower-alkyl, chloro-lower-alkyl or fluoro-lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy Mé/10. 3 . 82 or acyloxy and the dotted 1,2-bond signifies an optional C-C bond, and, where R20 is a group -O-R20l~ a double bond can be present in the 16,17--position, and a compound of the formula R2 Rl R ~ r~C II
R4 NH~
in which Rl signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signifies hydrogen, lower-alkoxy, hydroxy--lower-alkoxy or two adjacent symbols R , R , R and R together signify methyl-enedioxy, and at least one symbol Rl, R2, R3 or R4 contains oxygen.
An acyloxy group can be derived from a saturated or unsaturated aliphatic carboxylic acid containing up to 7 C atoms such as formic acid, acetic acid, propionic acid, butyric acid, pivalic acid, valeric acid and oenanthic acid.
Cl 7-alkanoyloxy groups such as acetoxy, propionyloxy and butyryloxyarepreferred. Lower-alkyl groups can be straight-chain or branched-chain and can contain 1 to 6, preferably 1 to 4, carbon atoms. Examples of such groups are methyl, ethyl, propyl and n-butyl.
Preferred D-homosteroids of formula I are those which are unsaturated in the 1,2-position and R6 is hydrogen, R9 is hydrogen or fluorlne, Rl1 is hydroxy, R17a is acyloxy, especially Cl 7-alkanoyloxy, R20 is a group -CH2-R 1 and R21 is acyloxy, especially Cl 7-alkanoyloxy, or hydrogen or hydroxy. Especially preferred are the 1,2-unsaturated D-homosteroids of formula I in which R6 and R9 are hydrogen, Rll is hydroxy, R17a is propionyloxy or especiallybutyryloxy, R20 is a group -C~2-R21 and R21 is acetoxy, hydroxy or especially hydrogen. Examples of preferred D-homosteroids of formula I are:
17a-Butyryloxy-9-fluoro~ -hydroxy-D-homopregna--1,4-diene-3,20-dione;
21-acetoxy-9-fluoro-11~-hydroxy-17a-propionyloxy-D--homopregna-1,4-diene-3,20-dione;
17a-butyryloxy-11~,21-dihydroxy-D-homopregna-1,4--diene-3,20-dione; and especially 17a-butyryloxy-11~-hydroxy-D-homopregna-1,4-diene--3,20-dione.
Examples of other D-homosteroids of formula I are:
21-Chloro-11~,17a-dihydroxy-9-fluoro-D-homopregna-l, 4-diene-3,20-dione;
17a-butyryloxy-21-chloro 9-fluoxo~ -hydroxy-D-homo-pregna 1,4-diene-3,20-dione;
17a,21-diacetoxy-9-fluoro~ -hydroxy-D-homopregna--1,4-diene-3,20-dione;
17a-butyryloxy~ ,21-dihydroxy-9-fluoro-D-homopregna--1,4-diene-3,20-dione;
9-chloro-17a,21-dihydroxy-11~-hydroxy-D-homopregna--1,4-diene-3,2C-dione;
21-acetoxy-9-fluoro-11~-hydroxy-17a-propionyloxy-D--homopregn-4-ene-3,20-dione;
17a-butyryloxy-11~-hydroxy-D-homopregn-4-ene-3,20--dione;
ll~-hydroxy-3-oxo-17a-propionyloxy-D-homoandrosta- --1,4-diene-17a~-carboxylic a~id methyl ester;
llB-hydroxy-3-oxo-17a-propionyloxy-D-homoandrosta--1,4-diene-17a~-carboxylic acid chloromethyl ester;
17a-acetoxy-6a,9-difluoro-11~-hydroxy-3-oxo-~-homo-androsta-1,4-diene-17a~-carboxylic acid methyl ester.
Preferred compounds of formula II in the scope of the present invention are those in which Rl and R4 are hydrogen, R2 is ethoxy, isopropoxy or especially butoxy and R3 is metho~y, especially D,L-4-(3-butoxy 4-methoxy~
benzyl)-2-imidazolidinone.
Compounds of formula II are described, for example, in German published Patent Specification 2 108 438.
Further, it is known, for example from German yublished Patent Specifications 2 614 079 and 2 ~38 363 and European published Patent Specification 13 959, that D-homosteroids haue an intiinfla~natory activity. It has now been found that this activity is increased in a surprising manner by compounds of formula II.
The preparations in accordance with the invention can be used for the therapy of inflammatory and allergic dermatological conditions such as psoriasis, eczema (e.g.
chronic eczema), dermatitis (e.g. contact dermatitis and neurodermatitis) and related diseases. The invention is concerned with the use of said preparations in the treatment of inflammatory and allergic dermatological conditions, as well as a method for the treatment of such conditions by administration of the preparations in accordance with the inventionO
Examples of topical application forms of the prep-arations in accordance with the invention are fatty ointments, ointments, creams, hydrophilic creams, gels and lotions.
~ 6 --Conveniently, in the preparations in accordance with the invention the concentration of a D-homosteroid of formula I amounts to between about 0.001% and 0.5%, preferably between about 0.005~ and 0.05~, and the S concentration of a compound of formula II amounts to between about 0.5% and 10%, preferably between about 2% and 5%.
The pr~parations in accordance with the invention can contain one or more D-homosteroids of formula I or one or more compounds of formula II.
In accordance wi.th another aspect of the invention, the present invention provides a process for the preparation of topically applicable pharmaceutical compositions, which process comprises mixing a D-homosteroid of the formula I above and a compound of the formula II above, concentration of the D-homosteroi of formula I amounting to between about 0.001 and 0.5% and that of the compound of formula II to between about 0.5 and 10%, by weight, and bringing the mixture into a suitable topically applicable galenical form. The techniques for effecting this are familiar to any person skilled in the art. They involve mixing the active substance components with suitable non-toxic, inert, compatible solid or liquid carriQr materials, including the usual adjuvants such as stabilizing, preserving, wetting or emulsifying agents.
1~
~ 7 --The following Examples illustrate the present invention:
Example 1 An ointment hav~ng the following composition is manufactured in a manner known per ~e:
17a-Butyryloxy~ hydroxy-D--homopregna-1,4~diene-3,20-dione * 0.05 g or 0.01 g D,~-4-(3-Butoxy-4~methoxybenzyl)-
The present invention is concerned with topically applicable pharmaceutical preparations which have, in particular, antiinflammatory activity. The preparations in accordance with the invention contain as the active substances a D-homosteroid of the formula coR2c~
R1~Rl?a I
~6 in which R6 signified hydrogen, methyl, chlorine or fluorine, R signifies hydrogen, fluorine or chlorine, Rll signifies oxo or (~-H,~ OH), R 7a sig-nifies hydroxy or acyloxy, R20 signifies a group O-R20l or -CH _R21 R201 nifies lower-alkyl, chloro-lower-alkyl or fluoro-lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy Mé/10. 3 . 82 or acyloxy and the dotted 1,2-bond signifies an optional C-C bond, and, where R20 is a group -O-R20l~ a double bond can be present in the 16,17--position, and a compound of the formula R2 Rl R ~ r~C II
R4 NH~
in which Rl signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signifies hydrogen, lower-alkoxy, hydroxy--lower-alkoxy or two adjacent symbols R , R , R and R together signify methyl-enedioxy, and at least one symbol Rl, R2, R3 or R4 contains oxygen.
An acyloxy group can be derived from a saturated or unsaturated aliphatic carboxylic acid containing up to 7 C atoms such as formic acid, acetic acid, propionic acid, butyric acid, pivalic acid, valeric acid and oenanthic acid.
Cl 7-alkanoyloxy groups such as acetoxy, propionyloxy and butyryloxyarepreferred. Lower-alkyl groups can be straight-chain or branched-chain and can contain 1 to 6, preferably 1 to 4, carbon atoms. Examples of such groups are methyl, ethyl, propyl and n-butyl.
Preferred D-homosteroids of formula I are those which are unsaturated in the 1,2-position and R6 is hydrogen, R9 is hydrogen or fluorlne, Rl1 is hydroxy, R17a is acyloxy, especially Cl 7-alkanoyloxy, R20 is a group -CH2-R 1 and R21 is acyloxy, especially Cl 7-alkanoyloxy, or hydrogen or hydroxy. Especially preferred are the 1,2-unsaturated D-homosteroids of formula I in which R6 and R9 are hydrogen, Rll is hydroxy, R17a is propionyloxy or especiallybutyryloxy, R20 is a group -C~2-R21 and R21 is acetoxy, hydroxy or especially hydrogen. Examples of preferred D-homosteroids of formula I are:
17a-Butyryloxy-9-fluoro~ -hydroxy-D-homopregna--1,4-diene-3,20-dione;
21-acetoxy-9-fluoro-11~-hydroxy-17a-propionyloxy-D--homopregna-1,4-diene-3,20-dione;
17a-butyryloxy-11~,21-dihydroxy-D-homopregna-1,4--diene-3,20-dione; and especially 17a-butyryloxy-11~-hydroxy-D-homopregna-1,4-diene--3,20-dione.
Examples of other D-homosteroids of formula I are:
21-Chloro-11~,17a-dihydroxy-9-fluoro-D-homopregna-l, 4-diene-3,20-dione;
17a-butyryloxy-21-chloro 9-fluoxo~ -hydroxy-D-homo-pregna 1,4-diene-3,20-dione;
17a,21-diacetoxy-9-fluoro~ -hydroxy-D-homopregna--1,4-diene-3,20-dione;
17a-butyryloxy~ ,21-dihydroxy-9-fluoro-D-homopregna--1,4-diene-3,20-dione;
9-chloro-17a,21-dihydroxy-11~-hydroxy-D-homopregna--1,4-diene-3,2C-dione;
21-acetoxy-9-fluoro-11~-hydroxy-17a-propionyloxy-D--homopregn-4-ene-3,20-dione;
17a-butyryloxy-11~-hydroxy-D-homopregn-4-ene-3,20--dione;
ll~-hydroxy-3-oxo-17a-propionyloxy-D-homoandrosta- --1,4-diene-17a~-carboxylic a~id methyl ester;
llB-hydroxy-3-oxo-17a-propionyloxy-D-homoandrosta--1,4-diene-17a~-carboxylic acid chloromethyl ester;
17a-acetoxy-6a,9-difluoro-11~-hydroxy-3-oxo-~-homo-androsta-1,4-diene-17a~-carboxylic acid methyl ester.
Preferred compounds of formula II in the scope of the present invention are those in which Rl and R4 are hydrogen, R2 is ethoxy, isopropoxy or especially butoxy and R3 is metho~y, especially D,L-4-(3-butoxy 4-methoxy~
benzyl)-2-imidazolidinone.
Compounds of formula II are described, for example, in German published Patent Specification 2 108 438.
Further, it is known, for example from German yublished Patent Specifications 2 614 079 and 2 ~38 363 and European published Patent Specification 13 959, that D-homosteroids haue an intiinfla~natory activity. It has now been found that this activity is increased in a surprising manner by compounds of formula II.
The preparations in accordance with the invention can be used for the therapy of inflammatory and allergic dermatological conditions such as psoriasis, eczema (e.g.
chronic eczema), dermatitis (e.g. contact dermatitis and neurodermatitis) and related diseases. The invention is concerned with the use of said preparations in the treatment of inflammatory and allergic dermatological conditions, as well as a method for the treatment of such conditions by administration of the preparations in accordance with the inventionO
Examples of topical application forms of the prep-arations in accordance with the invention are fatty ointments, ointments, creams, hydrophilic creams, gels and lotions.
~ 6 --Conveniently, in the preparations in accordance with the invention the concentration of a D-homosteroid of formula I amounts to between about 0.001% and 0.5%, preferably between about 0.005~ and 0.05~, and the S concentration of a compound of formula II amounts to between about 0.5% and 10%, preferably between about 2% and 5%.
The pr~parations in accordance with the invention can contain one or more D-homosteroids of formula I or one or more compounds of formula II.
In accordance wi.th another aspect of the invention, the present invention provides a process for the preparation of topically applicable pharmaceutical compositions, which process comprises mixing a D-homosteroid of the formula I above and a compound of the formula II above, concentration of the D-homosteroi of formula I amounting to between about 0.001 and 0.5% and that of the compound of formula II to between about 0.5 and 10%, by weight, and bringing the mixture into a suitable topically applicable galenical form. The techniques for effecting this are familiar to any person skilled in the art. They involve mixing the active substance components with suitable non-toxic, inert, compatible solid or liquid carriQr materials, including the usual adjuvants such as stabilizing, preserving, wetting or emulsifying agents.
1~
~ 7 --The following Examples illustrate the present invention:
Example 1 An ointment hav~ng the following composition is manufactured in a manner known per ~e:
17a-Butyryloxy~ hydroxy-D--homopregna-1,4~diene-3,20-dione * 0.05 g or 0.01 g D,~-4-(3-Butoxy-4~methoxybenzyl)-
-2-im1dazolidinone * 5 g 10 Vaseline, white 35 g Wax, white 4 g Paraffin oil, viscous 18.995 g or 18.990 g DEHYMULS E ** 7 . g Water, deionized ad 100 g * finely ground ** high molecular weight aliphatic mixed ester; supplier:
Deutsche Hydrierwerke Example 2 An ointment having the following composition is manufactured in a manner known per se:
*Trademark ~,. , L.' ~ ~ .
~ 8 --17a-Buty.ryloxy-9-fluoro~
-hydroxy-D-homopregna-1,4--diene-3,20-dione 0.01 g or 0.005 g D,L-4-(3-Butoxy-4-methoxy-5 benzyl~-2-imidazolidinone 2.5 g Vaseline, white 35 g Wax, white 5 Y
Paraffin oil, viscous19 g DEHYMULS E 7 g 10 Water, deioniæed ad 100 g Example 3 A fatty ointment having the following composition is manufactured in a manner known per se:
17a-Butyryloxy-11~,21-dihydroxy--D-homopregna-1,4-diene-3,20-dione 0.01 g or 0.05 g D,L-4-(3-Butoxy-4-methoxy-benzyl)-2-imida~olidinone 2.5 g Paraffin oil 10 g Wax, microcrystalline 15 g 20 Vaseline 72.5 g - 9 .-Exam~e_4 A cream having the following composition is manu-factured in a manner known per se:
21-Acetoxy~9-fluoro~ -hydroxy-5 -17a-propionyloxy-D homopregna-1,4--diene-3,20 dione . 0~01 g or 0.02 g DJ1-4- (3-Butoxy-4-methoxy-benzyl)-2-imidazolidinon~ 4.0 Glycerine monostearateio.o g 10 Tween ~0 * 2.0 g Cetyl alcohol S.0 g Paraffin oil, viscous7.0 g Methyl paraben **0.15 g Propylene glycol 20.0 g 15 Water, deionized ad 100 g * Polyethylene oxide sorbitan stearate ** Methyl 4~hydroxybenzoate ExamE~ 5 Preparations corresponding to Examples 1-4 are 20 manufactured in a manner known per se using 0.01 g or 0.03 g of 17a-butyryloxy-21-chloro-9-fluoro-11~-hydroxy-D~homo-pregna-1,4-diene-3,20-dione as the active substance *Trademark component of formula I, 3.0 g of D,L-4-(3 isopropoxy-4--methoxybenzyl)-2-imidazolidinone (microni2ed) as the active substance component of formula II and the same carriers and excipients as in Examples 1-4.
Deutsche Hydrierwerke Example 2 An ointment having the following composition is manufactured in a manner known per se:
*Trademark ~,. , L.' ~ ~ .
~ 8 --17a-Buty.ryloxy-9-fluoro~
-hydroxy-D-homopregna-1,4--diene-3,20-dione 0.01 g or 0.005 g D,L-4-(3-Butoxy-4-methoxy-5 benzyl~-2-imidazolidinone 2.5 g Vaseline, white 35 g Wax, white 5 Y
Paraffin oil, viscous19 g DEHYMULS E 7 g 10 Water, deioniæed ad 100 g Example 3 A fatty ointment having the following composition is manufactured in a manner known per se:
17a-Butyryloxy-11~,21-dihydroxy--D-homopregna-1,4-diene-3,20-dione 0.01 g or 0.05 g D,L-4-(3-Butoxy-4-methoxy-benzyl)-2-imida~olidinone 2.5 g Paraffin oil 10 g Wax, microcrystalline 15 g 20 Vaseline 72.5 g - 9 .-Exam~e_4 A cream having the following composition is manu-factured in a manner known per se:
21-Acetoxy~9-fluoro~ -hydroxy-5 -17a-propionyloxy-D homopregna-1,4--diene-3,20 dione . 0~01 g or 0.02 g DJ1-4- (3-Butoxy-4-methoxy-benzyl)-2-imidazolidinon~ 4.0 Glycerine monostearateio.o g 10 Tween ~0 * 2.0 g Cetyl alcohol S.0 g Paraffin oil, viscous7.0 g Methyl paraben **0.15 g Propylene glycol 20.0 g 15 Water, deionized ad 100 g * Polyethylene oxide sorbitan stearate ** Methyl 4~hydroxybenzoate ExamE~ 5 Preparations corresponding to Examples 1-4 are 20 manufactured in a manner known per se using 0.01 g or 0.03 g of 17a-butyryloxy-21-chloro-9-fluoro-11~-hydroxy-D~homo-pregna-1,4-diene-3,20-dione as the active substance *Trademark component of formula I, 3.0 g of D,L-4-(3 isopropoxy-4--methoxybenzyl)-2-imidazolidinone (microni2ed) as the active substance component of formula II and the same carriers and excipients as in Examples 1-4.
Claims (16)
1. A process for the preparation of topically applicable pharmaceutical compositions, which process comprises mixing a D-homosteroid of the formula I
in which R6 signifies hydrogen, methyl, chlorine or fluorine, R9 signifies hydrogen, fluorine or chlorine, R11 signifies oxo or (.alpha.-H,.beta.-OH), R17a sig-nifies hydroxy or acyloxy, R20 sig-nifies a group -O-R201 or -CH2-R21 R201 signifies lower-alkyll chloro--lower-alkyl or fluoro-lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy or acyloxy and the dotted 1,2--bond signifies an optional C-C bond, and, where R20 is a group -O-R201, a double bond can be present in the 16,17--position, and a compound of the formula II
in which R1 signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signify hydrogen, lower-alkoxy, hydroxy-lower-alkoxy or two adjacent symbols R1, R2, R3 and R4 together signify methylene-dloxy, and at least one symbol R1, R2, R3 or R4 contains oxygen, the concentration of the D-homosteroid of formula I amounting to between about 0.001 and 0.5% and that of the compound of formula II to between about 0.5 and 10%, by weight, and bringing the mixture into a suitable topically applicable galenical form.
in which R6 signifies hydrogen, methyl, chlorine or fluorine, R9 signifies hydrogen, fluorine or chlorine, R11 signifies oxo or (.alpha.-H,.beta.-OH), R17a sig-nifies hydroxy or acyloxy, R20 sig-nifies a group -O-R201 or -CH2-R21 R201 signifies lower-alkyll chloro--lower-alkyl or fluoro-lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy or acyloxy and the dotted 1,2--bond signifies an optional C-C bond, and, where R20 is a group -O-R201, a double bond can be present in the 16,17--position, and a compound of the formula II
in which R1 signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signify hydrogen, lower-alkoxy, hydroxy-lower-alkoxy or two adjacent symbols R1, R2, R3 and R4 together signify methylene-dloxy, and at least one symbol R1, R2, R3 or R4 contains oxygen, the concentration of the D-homosteroid of formula I amounting to between about 0.001 and 0.5% and that of the compound of formula II to between about 0.5 and 10%, by weight, and bringing the mixture into a suitable topically applicable galenical form.
2. A process according to claim 1, wherein the D-homosteroid of formula I is unsaturated in the 1,2-position and R6 is hydrogen, R9 is hydrogen or fluorine, R11 is hydroxy, R17a is acyloxy, especially C1-7-alkanoyloxy, R20 is a group -CH2-R21 and R21 is acyloxy, especially C1-7-alkanoyloxy, or hydrogen or hydroxy.
3. A process according to claim 2, wherein in the D-homo-steroid of formula I a double bond is present in the 1,2-position and R6 and R9 are hydrogen, R11 is hydroxy, R17a is propionyloxy or especially butyryloxy, R20 is a group -CH2-R21 and R21 is acetoxy, hydroxy or especially hydrogen.
4. A process according to claim 1, wherein the D-homosteroid is 17a-butyryloxy-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione.
5. A process according to claim 1, wherein in the compound of formula II R1 and R4 are hydrogen, R2 is ethoxy, isopropoxy or especially butoxy and R3 is methoxy.
6. A process according to claim 6, wherein the compound of formula II is D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone.
7. A process according to claim 1, wherein the D-homosteroid is 17a-butyryloxy-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione, 17a-butyryloxy-9-fluoro-11.beta.-hydroxy-D-homopregna-1,4-diene-3, 20-dione, 21-acetoxy-9-fluoro-11.beta.-hydroxy-17a-propionyloxy-D-homopregna-1,4-diene-3,20-dione, 17a-butyryloxy-11.beta., 21-dihydro-D-homopregna-1,4-diene-3,20-dione or 17a-butyryloxy-21-chloro-9-fluoro-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione and the compound of formula II is D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone or D,L-4-(3-isopropoxy-4-methoxybenzyl)-2 imidazolidinone.
8. A process in accordance with claim 1 wherein the D-homo-steroid is 17a-butyryloxy-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione and the compound of formula II is D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone.
9. A composition for topical application, comprising a D-homosteroid of the formula I
in which R6 signifies hydrogen, methyl, chlorine or fluorine, R9 signifies hydrogen, fluorine or chlorine, R11 signifies oxo or (.alpha.-H,.beta.-OH), R17a sig-nifies hydroxy or acyloxy, R20 sig-nifies a group -O-R201 or -CH2-R21, R201 signifies lower-alkyl, chloro-lower-alkyl or fluoro-lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy or acyloxy and the dotted 1,2-bond signifies an optional C-C bond, and, where R20 is a group -O-R201, a double bond can be present in the 16, 17-position;
and a compound of the formula II
in which R1 signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signify hydrogen, lower-alkoxy, hydroxy-lower-alkoxy or two adjacent symbols R1, R2, R3 and R4 together signify methylene-dioxy, and at least one symbol R1, R2, R3 or R4 contains oxygen;
the concentration of the D-homosteroid of formula I amounting to between about 0.001 and 0.5%, and that of the compound of formula II to between about 0.5 and 10%, by weight, the mixture being in a suitable topically applicable galenical form.
in which R6 signifies hydrogen, methyl, chlorine or fluorine, R9 signifies hydrogen, fluorine or chlorine, R11 signifies oxo or (.alpha.-H,.beta.-OH), R17a sig-nifies hydroxy or acyloxy, R20 sig-nifies a group -O-R201 or -CH2-R21, R201 signifies lower-alkyl, chloro-lower-alkyl or fluoro-lower-alkyl, R21 signifies hydrogen, chlorine, fluorine, hydroxy or acyloxy and the dotted 1,2-bond signifies an optional C-C bond, and, where R20 is a group -O-R201, a double bond can be present in the 16, 17-position;
and a compound of the formula II
in which R1 signifies hydrogen, halogen, lower-alkyl or lower-alkoxy and R2, R3 and R4 signify hydrogen, lower-alkoxy, hydroxy-lower-alkoxy or two adjacent symbols R1, R2, R3 and R4 together signify methylene-dioxy, and at least one symbol R1, R2, R3 or R4 contains oxygen;
the concentration of the D-homosteroid of formula I amounting to between about 0.001 and 0.5%, and that of the compound of formula II to between about 0.5 and 10%, by weight, the mixture being in a suitable topically applicable galenical form.
10. A composition according to claim 9, wherein the D-homo-steroid of formula I is unsaturated in the 1,2-position and R6 is hydrogen, R9 is hydrogen or fluorine, R11 is hydroxy, R17a is acyloxy, especially C1-7 -alkanoyloxy, R20 is a group -CH2-R21 and R21 is acyloxy, especially C1-7-alkanoyl oxy, or hydrogen or hydroxy.
11. A composition according to claim 10, wherein in the D-homosteroid of formula I a double bond is present in the 1,2-position and R6 and R9 are hydrogen, R11 is hydroxy, R17a is propionyloxy or especially butyryloxy, R20 is a group -CH2-R21 and R21 is acetoxy, hydroxy or especially hydrogen.
12. A composition according to claim 9, wherein the D-homo-steroid is 17a-butyryloxy-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione.
13. A composition according to claim 9, wherein in the com-pound of formula II R1 and R4 are hydrogen, R2 is ethoxy, isopropoxy or especially butoxy and R3 is methoxy.
14. A composition according to claim 9, wherein the compound of formula II is D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazo-lidinone.
15. A composition according to claim 9, wherein the D-homo-steroid is 17a-butyryloxy-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione, 17a-butyryloxy-9-fluoro-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione, 21-acetoxy 9-fluoro-11.beta.-hydroxy-17a-propionyloxy-D-homopregna-1,4-diene-3,20-dione, 17a-butyry-loxy-11.beta., 21-dihydro-D-homo-pregna-1,4-diene-3,20-dione or 17a-butyryloxy-21-chloro-9-fluoro-11.beta.-hydroxy-D-homopregna-1, 4-diene-3,20-dione and the compound of formula II is D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone or D,L-4-(3-isopropoxy-4-methoxybenzyl)-2-imidazolidinone.
16. A composition according to claim 9 wherein the D-homosteroid is 17a-butyryloxy-11.beta.-hydroxy-D-homopregna-1,4-diene-3,20-dione and the compound of formula II is D,L-4-(3-hutoxy-4-methoxybenzyl)-2-imidazolidinone.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH383581 | 1981-06-11 | ||
| CH3835/81 | 1981-06-11 | ||
| CH1080/82 | 1982-02-22 | ||
| CH108082 | 1982-02-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1188616A true CA1188616A (en) | 1985-06-11 |
Family
ID=25686591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000399814A Expired CA1188616A (en) | 1981-06-11 | 1982-03-30 | Pharmaceutical preparations |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0067347A1 (en) |
| AU (1) | AU8463582A (en) |
| CA (1) | CA1188616A (en) |
| DK (1) | DK175782A (en) |
| IL (1) | IL65976A0 (en) |
| NZ (1) | NZ200475A (en) |
| PH (1) | PH18457A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5972922A (en) * | 1990-06-11 | 1999-10-26 | Alcon Laboratories, Inc. | Steroids which inhibit angiogenesis |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5252319A (en) * | 1990-06-12 | 1993-10-12 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
| US5124154A (en) * | 1990-06-12 | 1992-06-23 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
| US5209926A (en) * | 1990-06-12 | 1993-05-11 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
| US5256408A (en) * | 1990-06-12 | 1993-10-26 | Insite Vision Incorporated | Aminosteroids for ophthalmic use |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3636039A (en) * | 1970-02-24 | 1972-01-18 | Hoffmann La Roche | Substituted benzylimidazolidinones |
| US4034087A (en) * | 1973-12-17 | 1977-07-05 | The Regents Of The University Of Michigan | Pharmaceutical composition and process of treatment |
| SE427276B (en) * | 1975-04-03 | 1983-03-21 | Hoffmann La Roche | PROCEDURE FOR PREPARING D-HOMOSTEROIDS |
| US4144332A (en) * | 1976-01-05 | 1979-03-13 | The Regents Of The University Of Michigan | Process for alleviating proliferative skin diseases |
| AT356301B (en) * | 1976-09-03 | 1980-04-25 | Hoffmann La Roche | METHOD FOR THE PRODUCTION OF NEW D-HOMOSTEROIDS |
| CA1138857A (en) * | 1979-01-24 | 1983-01-04 | Leo Alig | D-homosteroids |
-
1982
- 1982-03-30 CA CA000399814A patent/CA1188616A/en not_active Expired
- 1982-04-20 DK DK175782A patent/DK175782A/en not_active Application Discontinuation
- 1982-04-30 NZ NZ200475A patent/NZ200475A/en unknown
- 1982-04-30 PH PH27226A patent/PH18457A/en unknown
- 1982-05-28 EP EP82104732A patent/EP0067347A1/en not_active Withdrawn
- 1982-06-04 IL IL65976A patent/IL65976A0/en unknown
- 1982-06-07 AU AU84635/82A patent/AU8463582A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5972922A (en) * | 1990-06-11 | 1999-10-26 | Alcon Laboratories, Inc. | Steroids which inhibit angiogenesis |
Also Published As
| Publication number | Publication date |
|---|---|
| DK175782A (en) | 1982-12-12 |
| IL65976A0 (en) | 1982-09-30 |
| AU8463582A (en) | 1982-12-16 |
| PH18457A (en) | 1985-07-18 |
| NZ200475A (en) | 1985-08-30 |
| EP0067347A1 (en) | 1982-12-22 |
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