Patent EP-0206219-B1 (EP)
IPC: C07D311/22
Filed: 1986-06-16
Granted: 1989-09-06
Abstract: 1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, NL Photostable mixture of a sydnone imine of the general formula I  see diagramm : EP0206219,P28,F7  wherein R**1 denotes hydrogen, alkyl having 1 to 5 C atoms or halogen, R**2 denotes hydrogen, -NO, -COR**4 or -SO2 R**5 and R**3 denotes one of the radicals  see diagramm : EP0206219,P28,F9  or  see diagramm : EP0206219,P28,F11  wherein A represents oxygen or one of the groups  see diagramm : EP0206219,P28,F2   see diagramm : EP0206219,P28,F3   see diagramm : EP0206219,P28,F4  or  see diagramm : EP0206219,P28,F5  and m represents 0, 1 or 2 and n represents 2, 3, 4 or 5, and R**4 denotes hydrogen, an aliphatic radical which has 1 to 6 C atoms and which can also be substituted by alkoxy having 1 to 6 C atoms of araloxy having 6 to 12 C atoms, a cycloaliphatic radical having 5 to 8 C atoms, a bicycloaliphatic radical having 7 to 14 C atoms, a tricycloaliphatic radical having 7 to 16 C atoms, aryl which has 6 to 12 C atoms and which can also be monosubstituted, disubstituted or trisubstituted by halogen and/or alkyl having 1 to 4 C atoms and/or alkoxy having 1 to 4 C atoms, aralkyl or aralkenyl having 7 to 13 C atoms, alkoxy having 1 to 6 C atoms, cycloalkoxy having 5 to 8 C atoms, bicycloalkoxy having 7 to 12 C atoms, tricycloalkoxy having 7 to 16 C atoms, aryloxy having 6 to 12 C atoms, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl or alkoxycarbonyl having a total of 2 to 7 C atoms, R**5 denotes alkyl having 1 to 6 C atoms or aryl which has 6 to 12 C atoms and which can also be substituted by methyl or chlorine, or R**5 denotes a dialkylamino group having 1 to 4 C atoms in each of the alkyl radicals, R**6 and R**7 independently of one another denote alkyl having 1 to 6 C atoms, alkenyl having 3 to 6 C atoms, cycloalkyl having 5 to 8 C atoms, bicycloalkyl having 7 to 14 C atoms, tricycloalkyl having 7 to 16 C atoms or aralkyl having 7 to 9 C atoms, it being possible for the aralkyl group to be substituted by methyl or halogen, or denote a heterocyclic ring attached via an alkylene chain to the nitrogen atom of the 3-amino group, and R**6 additionally can be hydrogen and R**7 additionally can be a radical of the formula  see diagramm : EP0206219,P28,F8  R**8 denotes alkyl having 1 to 4 C atoms, R**9 denotes alkyl having 1 to 6 C atoms or aryl which has 6 to 12 C atoms and can also be substituted by methyl or chlorine, or R**9 denotes a dialkylamino group having 1 to 4 C atoms in each of the alkyl radicals, R**10 denotes alkyl having 1 to 4 C atoms and R**11 denotes alkyl having 1 to 6 C atoms, or a salt of the sydnone imine, a photostabilizer of the general formula II  see diagramm : EP0206219,P28,F10  wherein T**1 denotes hydrogen, alkyl having 1 or 2 C atoms, beta-hydroxyethyl or a radical G, T**2 denotes hydrogen, alkyl having 1 or 2 C atoms or alkanoyloxy having 1 to 4 C atoms, T**3 denotes hydrogen or alkyl having 1 or 2 C atoms, Y denotes a hydroxyl group, alkoxy having 1 or 2 C atoms or beta-hydroxyethoxy and Z denotes a group of the formula  see diagramm : EP0206219,P29,F2 or Y and Z together denote a structural element of the formulae III, IV or V  see diagramm : EP0206219,P29,F4   see diagramm : EP0206219,P29,F7   see diagramm : EP0206219,P29,F8  in which the free oxygen valency is attached in the Y-position and the free carbon valency is attached in the Z-position, and W**1 is hydrogen or one of the groups -OH, alkoxy having 1 or 2 C atoms or -OG, W**2 is hydrogen or one of the groups -OH and -OG, W**3 is hydrogen or one of the groups -OH, alkoxy having 1 or 2 C atoms and beta-hydroxyethoxy, W**4 is hydrogen or one of the groups -OH, alkoxy having 1 or 2 C atoms and beta-hydroxyethoxy, W**5 is hydrogen or -OH, W**6 is hydrogen or -OH and G is the radical of a monosaccharide or disaccharide, and/or an ester of these compounds with acids and also, if appropriate, a salt thereof with bases, and, if appropriate, further auxiliaries and additives, with the exception of a mixture of molsidomine and one or more photostabilizers of the general formula VI  see diagramm : EP0206219,P29,F1  wherein Y**1 is a hydroxyl group, alkoxy having 1 or 2 C atoms or beta-hydroxyethoxy and Z**1 is a group of the formula see diagramm : EP0206219,P29,F3  or Y**1 and Z**1 together denote a structural element of the formula VII or VIII  see diagramm : EP0206219,P29,F5   see diagramm : EP0206219,P29,F6  the free oxygen valency of which is attached in the Y**1 -position and the free carbon valency is attached in the Z**1 -position and R**21 is hydrogen or a radical G**1 , R**22 is hydrogen, alkyl having 1 or 2 C atoms or beta-hydroxyethyl, R**23 is hydrogen, alkyl having 1 or 2 C atoms or beta-hydroxyethyl, R**24 is hydrogen, alkyl having 1 or 2 C atoms or beta-hydroxyethyl or a radical G**1 and G**1 is the radical of a monosaccharide or disaccharide, or an ester of the compound of the formula VI with a pharmacologically acceptable acid as well as, if appropriate, its salt with a pharmacologically acceptable base. 1. Claims for the Contracting State AT : Process for stabilizing a sydnone imine of the general formula I  see diagramm : EP0206219,P31,F2  wherein R**1 denotes hydrogen, alkyl having 1 to 5 C atoms or halogen, R**2 denotes hydrogen, -NO, -COR**4 or -SO2 R**5 and R**3 denotes one of the radicals  see diagramm : EP0206219,P31,F4 or  see diagramm : EP0206219,P31,F6  wherein A represents oxygen or one of the groups  see diagramm : EP0206219,P31,F7   see diagramm : EP0206219,P31,F8   see diagramm : EP0206219,P31,F9  or  see diagramm : EP0206219,P31,F10  and m represents 0, 1 or 2 and n represents 2, 3, 4 or 5, and R**4 denotes hydrogen, an aliphatic radical which has 1 to 6 C atoms and which can also be substituted by alkoxy having 1 to 6 C atoms or aryloxy having 6 to 12 C atoms, a cycloaliphatic radical having 5 to 8 C atoms, a bicycloaliphatic radical having 7 to 14 C atoms, a tricycloaliphatic radical having 7 to 16 C atoms, aryl which has 6 to 12 C atoms and which can also be monosubstituted, disubstituted or trisubstituted by halogen and/or alkyl having 1 to 4 C atoms and/or alkoxy having 1 to 4 C atoms, aralkyl or aralkenyl having 7 to 13 C atoms, alkoxy having 1 to 6 C atoms, cycloalkoxy having 5 to 8 C atoms, bicycloalkoxy having 7 to 12 C atoms, tricycloalkoxy having 7 to 16 C atoms, aryloxy having 6 to 12 C atoms, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl or alkoxycarbonyl having a total of 2 to 7 C atoms, R**5 denotes alkyl having 1 to 6 C atoms or aryl which has 6 to 12 C atoms and which can also be substituted by methyl or chlorine, or R**5 denotes a dialkylamino group having 1 to 4 C atoms in each of the alkyl radicals, R**6 and R**7 independently of one another denote alkyl having 1 to 6 C atoms, alkenyl having 3 to 6 C atoms, cycloalkyl having 5 to 8 C atoms, bicycloalkyl having 7 to 14 C atoms, tricycloalkyl having 7 to 16 C atoms or aralkyl having 7 to 9 C atoms, it being possible for the aralkyl group to be substituted by methyl or halogen, or denote a heterocyclic ring attached via an alkylene chain to the nitrogen atom of the 3-amino group, and R**6 additionally can be hydrogen and R**7 additionally can be a radical of the formula  see diagramm : EP0206219,P31,F3  R**8 denotes alkyl having 1 to 4 C atoms, R**9 denotes alkyl having 1 to 6 C atoms or aryl which has 6 to 12 C atoms and can also be substituted by methyl or chlorine, or R**9 denotes a dialkylamino group having 1 to 4 C atoms in each of the alkyl radicals, R**10 denotes alkyl having 1 to 4 C atoms and R**11 denotes alkyl having 1 to 6 C atoms, or a salt of the sydnone imine, a photostabilizer of the general formula II  see diagramm : EP0206219,P31,F5  wherein T**1 denotes hydrogen, alkyl having 1 or 2 C atoms, beta-hydroxyethyl or a radical G, T**2 denotes hydrogen, alkyl having 1 or 2 C atoms or alkanoyloxy having 1 to 4 C atoms, T**3 denotes hydrogen or alkyl having 1 or 2 C atoms, Y denotes a hydroxyl group, alkoxy having 1 or 2 C atoms or beta-hydroxyethoxy and Z denotes a group of the formula  see diagramm : EP0206219,P31,F11  or Y and Z together denote a structural element of the formulae III, IV or V  see diagramm : EP0206219,P32,F2   see diagramm : EP0206219,P32,F4   see diagramm : EP0206219,P32,F6  in which the free oxygen valency is attached in the Y-position and the free carbon valency is attached in the Z-position, and W**1 is hydrogen or one of the groups -OH, alkoxy having 1 or 2 C atoms or -OG, W**2 is hydrogen or one of the groups -OH and -OG, W**3 is hydrogen or one of the groups -OH, alkoxy having 1 or 2 C atoms and beta-hydroxyethoxy, W**4 is hydrogen or one of the groups -OH, alkoxy having 1 or 2 C atoms and beta-hydroxyethoxy, W**5 is hydrogen or -OH, W**6 is hydrogen or -OH and G is the radical of a monosaccharide or disaccharide, and/or an ester of these compounds with acids and also, if appropriate, a salt thereof with bases, and, if appropriate, further auxiliaries and additives, with the exception of a process for photostabilizing molsidomine and of mixtures of molsidomine with mixing components wherein one or more compounds of the general formula VI  see diagramm : EP0206219,P32,F10  are added to the molsidoine or its mixtures ad photostabilizer, in which formula Y**1 is a hydroxyl group, alkoxy having 1 or 2 C atoms or beta-hydroxyethoxy and Z**1 is a group of the formula  see diagramm : EP0206219,P32,F1  or Y**1 and Z**1 together denote a structural element of the formula VII or VIII  see diagramm : EP0206219,P32,F3 see diagramm : EP0206219,P32,F5  the free oxygen valency of which is attached in the Y**1 -position and the free carbon valency is attached in the Z**1 -position and R**21 is hydrogen or a radical G**1 , R**22 is hydrogen, alkyl having 1 or 2 C atoms or beta-hydroxyethyl, R**23