US2005148768A1PendingUtilityA1

Cobalt-porphyrin complexes and use thereof as an anti-obesity agent

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Assignee: MIGENIX CORPPriority: Dec 15, 2000Filed: Nov 8, 2004Published: Jul 7, 2005
Est. expiryDec 15, 2020(expired)· nominal 20-yr term from priority
C07D 487/22A61P 3/04
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Claims

Abstract

Cobalt-porphyrin (Co-P) complexes for use as anti-obesity agents, and compositions and methods related thereto. The Co-P complexes exhibit reduced redox activity compared to cobalt mesoporphyrin (Co-MP) and cobalt protoporphyrin (Co-PP), which alleviates the deleterious effects associated with administration of Co-P associated with oxidative stress, particularly in the context of injection site toxicity.

Claims

exact text as granted — not AI-modified
1 . A cobalt-porphyrin complex having the structure:  
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein: 
 R 1  and R 2  are the same or different and independently —(CH 2 ) n -A-R 5 , wherein A is —C(═O)O—, —OC(═O)—, —C(═O)N(R)—, —N(R)C(═O)—, —C(═O)—, —N(R)—, —O— or —S—, and R is hydrogen, alkyl, substituted alkyl, arylalkyl, or substituted arylalkyl, and n is 2 or 3;  
 R 3  and R 4  are the same or different and independently —CH═CH 2  or —CH 2 CH 3 ;  
 R 5  is, at each occurrence, the same or different and independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl or substituted arylalkyl; and  
 L 1  and L 2  are optional ligands;  
 and with the proviso that the cobalt-porphyrin complex of structure (I) has no more than 5% of the redox activity of cobalt mesoporphyrin.  
 
     
     
         2 . The complex of  claim 1  wherein A is —C(═O)O—.  
     
     
         3 . The complex of  claim 1  wherein A is —OC(═O)—.  
     
     
         4 . The complex of  claim 1  wherein A is —C(═O)N(R)—.  
     
     
         5 . The complex of  claim 1  wherein A is —N(R)C(═O)—.  
     
     
         6 . The complex of  claim 1  wherein A is —C(═O)—.  
     
     
         7 . The complex of  claim 1  wherein A is —N(R)—.  
     
     
         8 . The complex of  claim 1  wherein A is —O—.  
     
     
         9 . The complex of  claim 1  wherein A is —S—.  
     
     
         10 . The complex of  claim 1  wherein n is 2.  
     
     
         11 . The complex of  claim 1  wherein n is 3.  
     
     
         12 . The complex of  claim 1  wherein R is hydrogen.  
     
     
         13 . The complex of  claim 1  wherein R is lower alkyl.  
     
     
         14 . The complex of  claim 1  wherein R 5  is hydrogen.  
     
     
         15 . The complex of  claim 1  wherein R 5  is alkyl.  
     
     
         16 . The complex of  claim 15  wherein R 5  is lower alkyl.  
     
     
         17 . The complex of  claim 1  wherein R 5  is substituted alkyl.  
     
     
         18 . The complex of  claim 1  wherein R 5  is aryl or substituted aryl.  
     
     
         19 . The complex of  claim 1  wherein R 5  is arylalkyl or substituted arylalkyl.  
     
     
         20 . The complex of  claim 19  wherein arylalkyl is benzyl.  
     
     
         21 . The complex of  claim 1  wherein R 3  and R 4  are the same.  
     
     
         22 . The complex of  claim 20  wherein R 3  and R 4  are —CH═CH 2 .  
     
     
         23 . The complex of  claim 20  wherein R 3  and R 4  are —CH 2 CH 3 .  
     
     
         24 . The complex of  claim 1  wherein at least one of L 1  or L 2  is present.  
     
     
         25 . The complex of  claim 1  wherein both L 1  and L 2  are present.  
     
     
         26 . The complex of  claim 25  wherein L 1  and L 2  are glycinate.  
     
     
         27 . The complex of  claim 25  wherein L 1  and L 2  are imidazole.  
     
     
         28 . The complex of  claim 25  wherein L 1  and L 2  are halogen.  
     
     
         29 . The complex of  claim 25  wherein L 1  and L 2  are a mono- or di-substituted amino.  
     
     
         30 . The complex of  claim 25  where L 1  and L 2  are a substituted or unsubstituted heterocycle.  
     
     
         31 . A composition comprising a compound of  claim 1  in combination with a pharmaceutically acceptable carrier.  
     
     
         32 . A method for treating obesity, comprising administering an effective amount of a composition comprising a cobalt-porphyrin complex and a pharmaceutically acceptable carrier, wherein the cobalt-porphyrin complex has the structure:  
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein: 
 R 1  and R 2  are the same or different and independently —(CH 2 ) n -A-R 5 , wherein A is —C(═O)O—, —OC(═O)—, —C(═O)N(R)—, —N(R)C(═O)—, —C(═O)—, —O— or —S—, and R is hydrogen, alkyl, substituted alkyl, arylalkyl, or substituted arylalkyl, and n is 2 or 3;  
 R 3  and R 4  are the same or different and independently —CH═CH 2  or —CH 2 CH 3 ;  
 R 5  is, at each occurrence, the same or different and independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl or substituted arylalkyl; and  
 L 1  and L 2  are optional ligands;  
 and with the proviso that the cobalt-porphyrin complex of structure (I) has no more than 50% of the redox activity of cobalt mesoporphyrin.  
 
     
     
         33 . The method of  claim 32  wherein the composition is administered by injection.  
     
     
         34 . The complex of  claim 32  wherein A is —C(═O)O—.  
     
     
         35 . The complex of  claim 32  wherein A is —OC(═O)—.  
     
     
         36 . The complex of  claim 32  wherein A is —C(═O)N(R)—.  
     
     
         37 . The complex of  claim 32  wherein A is —N(R)C(═O)—.  
     
     
         38 . The complex of  claim 32  wherein A is —C(═O)—.  
     
     
         39 . The complex of  claim 32  wherein A is —N(R)—.  
     
     
         40 . The complex of  claim 32  wherein A is —O—.  
     
     
         41 . The complex of  claim 32  wherein A is —S—.  
     
     
         42 . The complex of  claim 32  wherein n is  2 .  
     
     
         43 . The complex of  claim 32  wherein n is  3 .  
     
     
         44 . The complex of  claim 32  wherein R is hydrogen.  
     
     
         45 . The complex of  claim 32  wherein R is lower alkyl.  
     
     
         46 . The complex of  claim 32  wherein R 5  is hydrogen.  
     
     
         47 . The complex of  claim 32  wherein R 5  is alkyl.  
     
     
         48 . The complex of  claim 47  wherein R 5  is lower alkyl.  
     
     
         49 . The complex of  claim 32  wherein R 5  is substituted alkyl.  
     
     
         50 . The complex of  claim 32  wherein R 5  is aryl or substituted aryl.  
     
     
         51 . The complex of  claim 50  wherein R 5  is arylalkyl or substituted arylalkyl.  
     
     
         52 . The complex of  claim 51  wherein arylalkyl is benzyl.  
     
     
         53 . The complex of  claim 32  wherein R 3  and R 4  are the same.  
     
     
         54 . The complex of  claim 53  wherein R 3  and R 4  are —CH═CH 2 .  
     
     
         55 . The complex of  claim 53  wherein R 3  and R 4  are —CH 2 CH 3 .  
     
     
         56 . The complex of  claim 32  wherein one of L 1  or L 2  is present.  
     
     
         57 . The complex of  claim 32  wherein both L 1  and L 2  are present.  
     
     
         58 . The complex of  claim 57  wherein L 1  and L 2  are glycinate.  
     
     
         59 . The complex of  claim 57  wherein L 1  and L 2  are imidazole.  
     
     
         60 . The complex of  claim 57  wherein L 1  and L 2  are halogen.  
     
     
         61 . The complex of  claim 57  wherein L 1  and L 2  are a mono- or di-substituted amino.  
     
     
         62 . The complex of  claim 57  wherein, and L 2  are a substituted or unsubstituted heterocycle.

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