Aurone derivatives

Abstract

Substituted aurones of formula (I): ##STR1## wherein R 1 , R 2 R 3 , R 4 , R 5 and R 6 are the same or different and can each represent hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 3-8 cycloalkyl, optionally substituted phenyl, C 1-6 haloalkyl, amido, amino, cyano, hydroxy, nitro, C 2-4 alkenyl, carboxyl, tetrazol-5-yl and --CH═CHCOOH; or wherein R 1 and R 2 taken together can represent a group of formula --CH═CH--CH═CH-- provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is carboxyl, tetrazol-5-yl or --CH═CHCOOH; or a pharmaceutically-acceptable salt or ester thereof, are effective in the prophylactic chemotherapy of allergic conditions such as bronchial asthma.

What we claim is: .[.1. A compound of the formula ##STR9## in which in which R 1 ,R 2 ,R 3 ,R 4 ,R 5  and R 6  are the same or different and can each represent hydrogen, halogen, C 1-6  alkyl, C 1-6  alkoxy, C 3-8  cycloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, amino, cyano, hydroxy, nitro, C 2-4  alkenyl, carboxyl, tetrazol- 5-yl or --CH═CHCOOH; or in which R 1  and R 2  taken together represent a group of formula --CH═CH--CH═CH--; provided that at least one of R 1 ,R 2 ,R 3 ,R 4 ,R 5  and R 6  is carboxyl, tetrazol-5-yl or --CH═CHCOOH; or a pharmaceutically-acceptable salt or 
     
        ester thereof..]. .[.2.  A compound of the formula ##STR10## in which R 1 ,R 2 ,R 3 , R 4 ,R 5  and R 6  are the same or different and can each represent hydrogen, halogen, C 1-6  alkyl, C 1-6  alkoxy, C 3-8  cyloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, amino, cyano, hydroxy, nitro, C 2-4  alkenyl, carboxyl, tetrazol-5-yl or --CH═CHCOOH; or in which R 1  and R 2  taken together respresent a group of formula --CH═CH--CH═CH--; provided that at least one of R 1 ,R 2 ,R 3 ,R 4 ,R 5  and R 6  is carboxyl, tetrazol-5-yl or --CH═CHCOOH, and at least one of R 1 ,R 2  and R 3  is other than hydrogen; or a pharmaceutically-acceptable salt or 
     
     
        ester thereof..]. 3. A compound according to claim .[.2.]. .Iadd.20 .Iaddend.in which R 1  is C 1-4  alkyl, carboxyl or halogen, R 2  and R 3  are hydrogen, R 4  is carboxyl or --CH═CHCOOH, and 
     
     
        R 5  and R 6  are hydrogen. 4. A compound according to claim .[.2.]. .Iadd.3 .Iaddend.in which R 1  is C 1-4  alkyl or carboxyl, R 2  and R 3  are hydrogen, R 4  is carboxyl or --CH═CHCOOH, and R 5  and R 6  are hydrogen. .[.5. A compound of the formula ##STR11## in which R 1 ,R 2 ,R 3 ,R 4 ,R 5  and R 6  are the same or different and can each represent hydrogen, halogen, C 1-6  alkyl, C 1-6  alkoxy, C 3-8  cycloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, amino, cyano, hydroxy, nitro, C 2-4  alkenyl, carboxyl, tetrazol-5-yl or --CH═CHCOOH; or in which R 1  and R 2  taken together represent a group of formula --CH═CH--CH═CH--; provided that at least one of R 1 ,R 2 ,R 3 ,R 4 ,R 5  and R 6  is carboxyl, tetrazol-5-yl or --CH═CHCOOH and at least one of R 4 ,R 5  and R 6  is halogen, C 3-8  cycloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, cyano, nitro, carboxyl, tetrazol- 5-yl or --CH═CHCOOH, or a pharmaceutically acceptable salt or ester 
     
     
        thereof..]. 6. A compound according to claim 171 5.]. .Iadd.20 .Iaddend.in which at least one of R 1 ,R 2  and R 3  is other than hydrogen. .[.7. A compound according to claim 5 in which one of R 4 ,R 5  or 
     
     
        R 6  is carboxyl, tetrazol-5-yl or --CH═CH--COOH..]. 8. A process for preparing a compound according to claim .[.1 .]. .Iadd.16 .Iaddend.wherein .[.R 1 ,R 2 ,R 3 ,.]. R 4 , .[.R 5  or R 6  are .]. .Iadd.is .Iaddend.other than tetrazol-5-yl which comprises reacting a benzaldehyde of the formula ##STR12## with a reactant of the formula ##STR13## wherein R 7  when taken singly is CH 2  X; wherein X is a leaving group; and R 8  when taken singly is OH; and   
     
     
       R 7  and R 8  taken together form the group --CH 2  --O--. 9. A process for preparing a compound according to claim .[.1.]. .Iadd.16 .Iaddend.wherein .[.one of R 1 , R 2 , R 3 ,.]. R 4 , .[.R 5  or R 6  .]. is tetrazol-5-yl which comprises reacting a benzaldehyde of the formula ##STR14## with a reactant of the formula ##STR15## wherein R 7  when taken singly is CH 2  X; wherein X is a leaving group, R 8  when taken singly is OH and R 7  and R 8  when taken together are --CH 2  --O-- wherein .[.one of R 1 ,R 2 ,R 3 ,.]. R 4 ,.[.R 5  or R 6  .]. is cyano, and then reacting the aurone thus formed containing a cyano group with an azide to form the corresponding tetrazol-5-yl substituted   
     
     
        aurone. 10. A pharmaceutical formulation .Iadd.in unit dosage form .Iaddend.for use in treating immediate hypersensitivity conditions such as asthma which comprises as an active ingredient an effective amount of a compound according to claim .[.1.]. .Iadd.16 .Iaddend.associated with a 
     
     
        pharmaceutically-acceptable carrier therefor. 11. A pharmaceutical formulation .Iadd.in unit dosage form .Iaddend.for use in treating immediate hypersensitivity conditions such as asthma which comprises as an active ingredient an effective amount of a compound according to claim .[.2.]. .Iadd.17 .Iaddend.associated with a pharmaceutically-acceptable 
     
     
        carrier therefor. 12. A pharmaceutical formulation .Iadd.in unit dosage form .Iaddend.for use in treating immediate hypersensitivity conditions such as asthma which comprises as an active ingredient an effective amount of a compound according to claim .[.5.]. .Iadd.20 .Iaddend.associated with 
     
     
        a pharmaceutically-acceptable carrier therefor. 13. A method of prophylactic chemotherapy of immediate hypersensitivity conditions such as asthma which comprises administering to a human susceptible to such conditions a prophylactically effective amount of a compound according to 
     
     
        claim .[.1.]. .Iadd.16.Iaddend.. 14. A method of prophylactic chemotherapy of immediate hypersensitivity conditions such as asthma which comprises administering to a human susceptible to such conditions a prophylactically effective amount of a compound according to claim .[.2.]. 
     
     
        .Iadd.17.Iaddend.. 15. A method of prophylactic chemotherapy of immediate hypersensitivity conditions such as asthma which comprises administering to a human susceptible to such conditions a prophylactically effective amount of a compound according to claim .[.5.]. .Iadd.20 .Iaddend.. 
     
     
        .Iadd. 6.  A compound of the formula ##STR16## in which R 1 , R 2 , R 3 , R 5  and R 6  are the same or different can each represent hydrogen, halogen, C 1-6  alkyl, C 1-6  alkoxy, C 3-8  cycloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, amino, cyano, hydroxy, nitro or C 2-4  alkenyl, and R 4  is carboxyl, tetrazol-5-yl or --CH═CHCOOH; or in which R 1  and R 2  taken togehter represent a group of the formula --CH═CH--CH═CH; or a pharmaceutically-acceptable salt or ester 
     
     
        thereof. .Iaddend. .Iadd.17.  A compound of the formula ##STR17## in which R 1 , R 2 , R 3 , R 5  and R 6  are the same or different and can each represent hydrogen, halogen C 1-6  alkyl, C 1-6  alkoxy, C 3-8  cycloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, amino, cyano, hydroxy, nitro or C 2-4  alkenyl, and R 4  can be carboxyl, tetrazol-5-yl or --CH═CHCOOH; or in which R 1  and R 2  taken together represent a group of the formula --CH═CH--CH═CH--; provided that at least one of R 1 , R 2  and R 3  is other than hydrogen; or a 
     
     
        pharmaceutically-acceptable salt or ester thereof. .Iaddend. .Iadd.18.  A compound according to claim 17 in which R 1  is C 1-4  alkyl, C 1-4  alkoxy or halogen, R 4  is carboxyl or --CH═CHCOOH, and R 2 , R 3 , R 5  and R 6  are hydrogen. .Iaddend. .Iadd.19. A compound according to claim 18 in which R 1  is C 1-4  alkyl, R 4  is carboxyl or --CH═CHCOOH, and R 2 , R 3 , R 5  and 
     
     
        R 6  are hydrogen. .Iaddend. .Iadd.20.  A compound of the formula ##STR18## in which R 1 , R 2 , R 3 , R 5  and R 6  are the same or different and can each represent hydrogen, carboxyl, tetrazol-5-yl, --CH═CHCOOH, halogen, C 1-6  alkyl, C 1-6  alkoxy, C 3-8  cycloalkyl, optionally substituted phenyl, C 1-6  haloalkyl, amido, amino, cyano, hydroxy, nitro or C 2-4  alkenyl and R 4  is carboxyl, tetrazol-5-yl or --CH═CHCOOH; or in which R 1  and R 2  taken together represent a group of the formula --CH═CH--CH═CH--; or a pharmaceutically-acceptable salt or ester thereof. .Iaddend.