Substituted pyrroles

Abstract

Compounds of the formula wherein R1, R2, R3, R4, R5, R6, R7, X and Y have the signficance given in the description, are useful in the control or prevention of inflammatory, immunological, bronchopulmonary or cardiovascular disorders.

We claim: 
     
       1. A compound of the formula ##STR14## wherein R 1  signifies hydrogen, alkyl, aryl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, trialkylaminoalkyl, aminoalkylaminoalkyl, azidoalkyl, acylaminoalkyl, acylthioalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, alkylsulphinylalkyl, alkylsulphonylalkyl, alkylsulphonyloxyalkyl, alkylcarbonyloxyalkyl, cyanoalkyl, amidinoalkyl, isothiocyanatoalkyl, glucopyranosyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, hydroxyalkylthioalkyl, mercaptoalkylthioalkyl, arylthioalkyl or carboxyalkylthioalkyl or a group of the formula ##STR15## in which Het signifies a heterocyclyl group, W signifies NH, S or a bond,   T signifies NH or S   V signifies O, S, NH. NNO 2 , NCN or CHNO 2 ,   Z signifies alkylthio, amino, monoalkylamino or dialkylamino,   Im signifies 1-imidazolyl,   Ar signifies aryl, and   n stands for 2-6;   R 2  signifies hydrogen, alkyl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, acylaminoalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylthio or alkylsulphinyl;   R 3  signifies a carbocyclic or heterocyclic aromatic group;   R 4 , R 5 , R 6  and R 7  each independently signify hydrogen, halogen, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulphonyl;   and one of X and Y signifies O and the other signifies O, S, (H,OH) or (H,H); with the proviso that R 1  has a significance different from hydrogen when R 2  signifies hydrogen, R 3  signifies 3-indolyl or 6-hydroxy-3-indolyl, R 4 , R 5  and R 7  each signify hydrogen, R 6  signifies hydrogen or hydroxy and X and Y both signify O and when R 2  signifies hydrogen, R 3  signifies 3-indolyl, R 4 , R 5 , R 6  and R 7  each signify hydrogen, X signifies (H,H) and Y signifies O; or a pharmaceutically acceptable salt of acidic compounds of formula I with bases and of basic compounds of formula I with acids.     
     
     
       2. A compound according to claim 1, wherein R 1  signifies hydrogen, alkyl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, azidoalkyl, acylaminoalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, glucopyranosyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, hydroxyalkylthioalkyl, mercaptoalkylthioalkyl, arylthioalkyl or carboxyalkylthioalkyl. 
     
     
       3. A compound according to claim 2, wherein R 1  signifies alkyl or aminoalkyl. 
     
     
       4. A compound according to claim 1, wherein R 1  signifies isothiocyanatoalkyl or a group of formula (b) in which T signifies S, V signifies NH and Z signifies amino or in which T signifies NH, V signifies NH or NNO 2  and Z signifies amino. 
     
     
       5. A compound according to claim 4, wherein R 2  signifies hydrogen. 
     
     
       6. A compound according to claim 5, wherein R 3  signifies phenyl which is monosubstituted by halogen, alkyl, alkoxy, haloalkyl, nitro, amino, alkylthio, alkylsulphinyl or alkylsulphonyl. 
     
     
       7. A compound according to claim 5, wherein R 3  signifies a group of the formula ##STR16## wherein R 1' , R 2' , R 4' , R 5' , R 6'   and R 7'  have any of the values accorded to R 1 , R 2 , R 4 , R 5 , R 6  and R 7  in claim 1. 
     
     
       8. A compound according to claim 7, wherein R 4 , R 5 , R 6  and R 7  each signify hydrogen. 
     
     
       9. A compound according to claim 8, wherein R 1  signifies methyl, 3-aminopropyl, 3-isothio-cyanatopropyl or a group of formula (b) in which T signifies S, V signifies NH, Z signifies amino and n stands for 3 or in which T signifies NH, V signifies NH or NNO 2 , Z signifies amino and n stands for 3, R 2  signifies hydrogen, R 3  signifies phenyl which is mono-substituted by chlorine, bromine, methyl, methoxy, trifluoromethyl, nitro, amino, methylsulphinyl or methylsulphonyl or a group of formula (i) given in claim 7 in which R 1'   signifies methyl and R 2' , R 4' , R 5' , R 6'   and R 7'   each signify hydrogen, and R 4 , R 5 , R 6  and R 7  each signify hydrogen. 
     
     
       10. A compound in accordance with claim 1 selected from the group consisting of: 3-(2-Chlorophenyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3-(2-Nitrophenyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3,4-Bis(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3-[1-(3-Aminopropyl)-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione   1-[1-[3-(Amidinothio)propyl]-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3-(1-Methyl-3-indolyl)-4-[1-[3-(2-nitroguanidino)propyl]-3-indolyl]-1H-pyrrole-2,5-dione and   3-[1-(3-Isothiocyanatopropyl)-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione.   
     
     
       11. A pharmaceutical composition comprising an effective amount of a compound of the formula ##STR17## wherein R 1  signifies hydrogen, alkyl, aryl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, trialkylaminoalkyl, aminoalkylaminoalkyl, azidoalkyl, acylaminoalkyl, acylthioalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, alkylsulphinylalkyl, alkylsulphonylalkyl, alkylsulphonyloxyalkyl, alkylcarbonyloxyalkyl, cyanoalkyl, amidinoalkyl, isothiocyanatoalkyl, glucopyranosyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, hydroxyalkylthioalkyl, mercaptoalkylthioalkyl, arylthioalkyl or carboxyalkylthioalkyl or a group of the formula ##STR18## in which Het signifies a heterocyclyl group, W signifies NH, S or a bond,   T signifies NH or S,   V signifies O, S, NH, NNO 2 , NCN or CHNO 2 ,   Z signifies alkylthio, amino, monoalkylamino or dialkylamino,   Im signifies 1-imidazolyl,   Ar signifies aryl, and   n stands for 2-6;   R 2  signifies hydrogen, alkyl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, acylaminoalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylthio or alkylsulphinyl;   R 3  signifies a carbocyclic or heterocyclic aromatic group;   R 4 , R 5 , R 6  and R 7  each independently signify hydrogen, halogen, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, acylamino, monoalkylamino, dialkylamino, alkylthio, alkylsulphinyl or alkylsulphonyl;   and one of X and Y signifies O and the other signifies O, S, (H,OH) or (H,H); with the proviso that R 1  has a significance different from hydrogen when R 2  signifies hydrogen, R 3  signifies 3-indolyl or 6-hydroxy-3-indolyl, R 4 , R 5  and R 7  each signify hydrogen, R 6  signifies hydrogen or hydroxy and X and Y both signify O and when R 2  signifies hydrogen, R 3  signifies 3-indolyl, R 4 , R 5 , R 6  and R 7  each signify hydrogen, X signifies (H,H) and Y signifies O; or a pharmaceutically acceptable salt of acidic compounds of formula I with bases and of basic compounds of formula I with acids, and an inert carrier material.     
     
     
       12. A pharmaceutical composition in accordance with claim 11, wherein the compound of formula I is selected from the group consisting of: 3-(2-Chlorophenyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3-(2-Nitrophenyl)-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3,4-Bis(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3-[1-(3-Aminopropyl)-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione   1-[1-[3-(Amidinothio)propyl]-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione,   3-(1-Methyl-3-indolyl)-4-[1-[3-(2-nitroguanidino)propyl]-3-indolyl]-1H-pyrrole-2,5-dione, and   3-[1-(3-Isothiocyanatopropyl)-3-indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione. .Iadd.   
     
     
       13.  A compound of the formula, 3-(1-methyl-3-indolyl)-4-(1-methyl-6-nitro-3-indolyl)-1H-pyrrole-2,5-dione. .Iaddend..Iadd. 
     
     
       14.  A pharmaceutical composition, comprising an effective amount of 3-(1-methyl-3-indolyl)-4-(1-methyl-6-nitro-3-indolyl)-1H-pyrrole-2,5-dione and an inert carrier material. .Iaddend.