Biologically active methylene blue derivatives

Abstract

The present invention relates to a method of photodynamic therapy and to a method of inducing a photocytoxic effect which comprises applying to an area to be treated an effective amount of a compound of formula in which R 1 , R 2 , R 3 and R 4 each independently is an optionally-substituted linear, branched or cyclic hydrocarbon group, or R 1 and R 2 together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring or R 3 and R 4 together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; and where X P− is a counteranion and P is 1, 2 or 3; except for the compounds in which —NR 1 R 2 and —NR 3 R 4 are the same and are selected from —N(CH 3 ) 2 or —N(CH 2 CH 3 ) 2 ; and exposing the area to light to activate the compound.

1 .- 42 . (canceled) 
     
     
         43 . A method of medical treatment in a patient in need of treatment which method comprises applying to an area of a patient in need of treatment an effective amount of a compound of formula 
       
         
           
           
               
               
           
         
         in which R 1 , R 2 , R 3  and R 4  each independently is an optionally-substituted linear, branched or cyclic hydrocarbon group, or R 1  and R 2  together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring or R 3  and R 4  together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; 
         and where X P−  is a counteranion and P is 1, 2 or 3; 
         except for the compounds in which —NR 1 R 2  and —NR 3 R 4  are the same and are selected from —N(CH 3 ) 2  or —N(CH 2 CH 3 ) 2 . 
       
     
     
         44 . A method according to  claim 43 , wherein said medical treatment is photodynamic therapy. 
     
     
         45 . A method according to  claim 43 , wherein in said compound R 1 , R 2 , R 3 , R 4  each independently is linear or branched —C n H 2n Y wherein n is 1-6, Y is H and where X −P  represents Cl − , Br − , I − , F − , NO 3   − , HSO 4   − , CH 3 CO 2   −  or a dianion namely SO 4   2−  or H 2 PO 4   2 . 
     
     
         46 . A method according to  claim 43 , wherein —NR 1 R 2  and —NR 3 R 4  each independently is linear or branched —C n H 2n Y wherein n is 1-10 and Y is H, F, Cl, Br, I, —OH, —OCH 3 , —OC 2 H 5 , —OC 3 H 7 , —CN, —OCOCH 3  or phenyl, or R 1 , R 2 , R 3  and R 4  are independently cyclohexyl. 
     
     
         47 . A method according to  claim 43 , wherein the sum of the number of carbon atoms in chains represented by R 1 , R 2 , R 3  and R 4  is from 14 to 40. 
     
     
         48 . A method according to  claim 43 , wherein:
 R 1 , R 2 , R 3  and R 4  each represent n-propyl;   R 1 , R 2 , R 3  and R 4  each represent n-butyl;   R 1 , R 2 , R 3  and R 4  each represent n-pentyl;   R 1 , R 2 , R 3  and R 4  each represent iso-pentyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1  represents n-hexyl, R 2  represents n-hexyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1 , R 2 , R 3  and R 4  each represent iso-butyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents iso-pentyl and R 4  represents iso-pentyl;   R 1  represents ethyl, R 2  represents ethyl, R 3  represents   n-propyl and R 4  represents n-propyl;   R 1  represents n-pentyl; R 2  represents n-pentyl, R 3  represents n-propyl, R 4  represents n-propyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents n-pentyl and R 4  represents n-pentyl;   R 1  represents ethyl, R 2  represents cyclohexyl, R 3  represents ethyl and R 4  represents cyclohexyl;   R 1  represents methyl, R 2  represents methyl, R 3  represents n-propyl, R 4  represents n-propyl, and   R 1  represents ethyl, R 2  represents ethyl, R 3  represents   n-heptyl and R 4  represents n-heptyl.   
     
     
         49 . A method as claimed in  claim 43 , wherein in said compound R 1 , R 2 , R 3  and R 4  are the same and are selected from n-propyl, n-butyl, n-pentyl and n-hexyl. 
     
     
         50 . A method as claimed in  claim 43 , wherein R 1 , R 2 , R 3  and R 4  each represent n-butyl. 
     
     
         51 . A method of inducing a photocytoxic effect, comprising applying to an area to be treated an effective amount of a compound of formula 
       
         
           
           
               
               
           
         
         in which R 1 , R 2 , R 3  and R 4  each independently is an optionally-substituted linear, branched or cyclic hydrocarbon group, or R 1  and R 2  together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring or R 3  and R 4  together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; 
         and where X P−  is a counteranion and P is 1, 2 or 3; 
         except for the compounds in which —NR 1 R 2  and —NR 3 R 4  are the same and are selected from —N(CH 3 ) 2  or —N(CH 2 CH 3 ) 2 ; and 
         exposing the area to light to activate the compound. 
       
     
     
         52 . A method according to  claim 51 , wherein in said compound R 1 , R 2 , R 3 , R 4  each independently is linear or branched —C n H 2n Y wherein n is 1-6, Y is H and where X −P  represents Cl − , Br − , I − , F − , NO 3   − , HSO 4   − , CH 3 CO 2   −  or a dianion namely SO 4   2−  or H 2 PO 4   2 . 
     
     
         53 . A method according to  claim 51 , wherein the sum of the carbon atoms in chains represented by R 1 , R 2 , R 3  and R 4  is from 14 to 40. 
     
     
         54 . A method according to  claim 51 , wherein R 1 , R 2 , R 3  and R 4  each represent n-propyl;
 R 1 , R 2 , R 3  and R 4  each represent n-butyl;   R 1 , R 2 , R 3  and R 4  each represent n-pentyl;   R 1 , R 2 , R 3  and R 4  each represent iso-pentyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1  represents n-hexyl, R 2  represents n-hexyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1 , R 2 , R 3  and R 4  each represent iso-butyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents iso-pentyl and R 4  represents iso-pentyl;   R 1  represents ethyl, R 2  represents ethyl, R 3  represents   n-propyl and R 4  represents n-propyl;   R 1  represents n-pentyl; R 2  represents n-pentyl, R 3  represents n-propyl, R 4  represents n-propyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents n-pentyl and R 4  represents n-pentyl;   R 1  represents ethyl, R 2  represents cyclohexyl, R 3  represents ethyl and R 4  represents cyclohexyl;   R 1  represents methyl, R 2  represents methyl, R 3  represents n-propyl, R 4  represents n-propyl, and   R 1  represents ethyl, R 2  represents ethyl, R 3  represents n-heptyl and R 4  represents n-heptyl.   
     
     
         55 . A method as claimed in  claim 51 , wherein in said compound R 1 , R 2 , R 3  and R 4  are the same and are selected from n-propyl, n-butyl, n-pentyl and n-hexyl. 
     
     
         56 . A method as claimed in  claim 51 , wherein R 1 , R 2 , R 3  and R 4  each represent n-butyl. 
     
     
         57 . A method of photodynamic therapy which comprises applying to an area to be treated an effective amount of a compound of formula 
       
         
           
           
               
               
           
         
         in which R 1 , R 2 , R 3  and R 4  each independently is an optionally-substituted linear, branched or cyclic hydrocarbon group, or R 1  and R 2  together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring or R 3  and R 4  together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; 
         and where X P−  is a counteranion and P is 1, 2 or 3; 
         except for the compounds in which —NR 1 R 2  and —NR 3 R 4  are the same and are selected from —N(CH 3 ) 2  or —N(CH 2 CH 3 ) 2 ; and 
         exposing the area to light to activate the compound. 
       
     
     
         58 . A method according to  claim 57 , wherein in said compound R 1 , R 2 , R 3 , R 4  each independently is linear or branched —C n H 2n Y wherein n is 1-6, Y is H and where X −P  represents Cl − , Br − , I − , F − , NO 3   − , HSO 4   − , CH 3 CO 2   −  or a dianion namely SO 4   2−  or H 2 PO 4   2 . 
     
     
         59 . A method according to  claim 57 , wherein the sum of the carbon atoms in chains represented by R 1 , R 2 , R 3  and R 4  is from 14 to 40. 
     
     
         60 . A method according to  claim 57 , wherein R 1 , R 2 , R 3  and R 4  each represent n-propyl;
 R 1 , R 2 , R 3  and R 4  each represent n-butyl;   R 1 , R 2 , R 3  and R 4  each represent n-pentyl;   R 1 , R 2 , R 3  and R 4  each represent iso-pentyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1  represents n-hexyl, R 2  represents n-hexyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1 , R 2 , R 3  and R 4  each represent iso-butyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents iso-pentyl and R 4  represents iso-pentyl;   R 1  represents ethyl, R 2  represents ethyl, R 3  represents n-propyl and R 4  represents n-propyl;   R 1  represents n-pentyl; R 2  represents n-pentyl, R 3  represents n-propyl, R 4  represents n-propyl;   R 1  represents n-butyl, R 2  represents n-butyl, R 3  represents n-pentyl and R 4  represents n-pentyl;   R 1  represents ethyl, R 2  represents cyclohexyl, R 3  represents ethyl and R 4  represents cyclohexyl;   R 1  represents methyl, R 2  represents methyl, R 3  represents n-propyl, R 4  represents n-propyl, and   R 1  represents ethyl, R 2  represents ethyl, R 3  represents   n-heptyl and R 4  represents n-heptyl.   
     
     
         61 . A method as claimed in  claim 57 , wherein in said compound R 1 , R 2 , R 3  and R 4  are the same and are selected from n-propyl, n-butyl, n-pentyl and n-hexyl. 
     
     
         62 . A method as claimed in  claim 57 , wherein R 1 , R 2 , R 3  and R 4  each represent n-butyl.