Carbazole formulations for the treatment of psoriasis and angiogenesis

Abstract

The methods and compositions disclosed herein relate to using carbazole, and derivatives thereof to modify a signaling activity such as epidermal growth factor receptor (EGFR) signalling, and angiogenesis activity, in a cell.

1 . A method for treating disorders characterized by aberrant receptor signaling, comprising administering an effective amount of a carbazole, or a derivative thereof, having the general formula:  
     
       
         
         
             
             
         
       
       wherein, R1-R9 can be a hydrogen atom, halogen atom, alkyl group, trihaloalkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, amino group, aryl group, substituted aryl, heteroaryl group, heterocycloalkyl group, heterocycloalkenyl group, heteroalicyclic group, hydroxyl group, alkoxy group, cycloalkoxy group, aryloxy group, heteroaryloxy group, heteroalicycloxy group, thiohydroxy group, thioalkyoxy group, thiocycloalkoxy group, thioheteroaryloxy group, thioheteroalicycloxy group, cyano group, carbamyl group, C—O-carbamyl group, N-carbamyl group, O-thiocarbamyl group, N-thiocarbamyl group, silyl group, phosphonyl group, C-carboxy group, O-carboxy group, N-amido group, C-amido group, sulfinyl group, sulfonyl group, S-sulfonamido group, n-sulfonamido group, trihalomethanesulfonyl group, guanyl group, guanidine group, and trihalomethanesulfonamido group.  
     
   
   
       2 . The method of  claim 1 , wherein the aberrant receptor signaling is aberrant epidermal growth factor receptor signaling.  
   
   
       3 . The method of  claim 1  further comprising treating a disorder associated with angiogenesis.  
   
   
       4 . The method of  claim 1 , wherein R1-R9 are all hydrogen.  
   
   
       5 . The method of  claim 1 , wherein the carbazole is hydroxylated, oxidized, or halogenated.  
   
   
       6 . The method of  claim 1 , wherein the carbazole is carbamazepine.  
   
   
       7 . The method of  claim 5 , wherein the carbazole is selected from the group consisting of 2-hydroxy-carbazole, 3-hydroxy-carbazole, 4-hydroxy-carbazole, 2,2-hydroxycarbazole, and 2,4-hydroxycarbazole.  
   
   
       8 . The method of  claim 1 , wherein the carbazole is formulated in a pharmaceutically acceptable carrier for topical administration.  
   
   
       9 . The method of  claim 1 , wherein the carbazole comprises a carrier selected from the group consisting of ointments, gels, lotions, sprays, shampoos, powders, foams, and solutions.  
   
   
       10 . The method of  claim 9 , wherein the carbazole is present in the carrier at a concentration of 1-20% by weight.  
   
   
       11 . The method of  claim 1 , wherein the disorder is a skin disorder selected from the group consisting of psoriasis, acne, rosacea, and eczema.  
   
   
       12 . The method of  claim 1 , wherein the disorder is psoriasis.  
   
   
       13 . A method for treating disorders associated with a rac signaling pathway, comprising administering an effective amount of carbazole or a derivative thereof having the general formula:  
     
       
         
         
             
             
         
       
       wherein, R1-R9 can be a hydrogen atom, halogen atom, alkyl group, trihaloalkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, amino group, aryl group, substituted aryl, heteroaryl group, heterocycloalkyl group, heterocycloalkenyl group, heteroalicyclic group, hydroxyl group, alkoxy group, cycloalkoxy group, aryloxy group, heteroaryloxy group, heteroalicycloxy group, thiohydroxy group, thioalkyoxy group, thiocycloalkoxy group, thioheteroaryloxy group, thioheteroalicycloxy group, cyano group, carbamyl group, C—O-carbamyl group, N-carbamyl group, O-thiocarbamyl group, N-thiocarbamyl group, silyl group, phosphonyl group, C-carboxy group, O-carboxy group, N-amido group, C-amido group, sulfinyl group, sulfonyl group, S-sulfonamido group, N-sulfonamido group, trihalomethanesulfonyl group, guanyl group, guanidine group, and trihalomethanesulfonamido group.  
     
   
   
       14 . The method of  claim 13 , wherein R1-R9 are all hydrogen.  
   
   
       15 . The method of  claim 13 , wherein the carbazole is hydroxylated, oxidized, or halogenated.  
   
   
       16 . The method of  claim 13 , wherein the carbazole is carbamazepine.  
   
   
       17 . The method of  claim 15 , wherein the carbazole is selected from the group consisting of 2-hydroxy-carbazole, 3-hydroxy-carbazole, 4-hydroxy-carbazole, 2,2-hydroxy-carbazole, and 2,4-hydroxycarbazole.  
   
   
       18 . The method of  claim 13 , wherein the carbazole is formulated in a pharmaceutically acceptable carrier for topical administration.  
   
   
       19 . The method of  claim 13 , wherein the carbazole comprises a carrier selected from the group consisting of ointments, gels, lotions, sprays, shampoos, powders, foams, and solutions.  
   
   
       20 . The method of  claim 19 , wherein the carbazole is present in the carrier at a concentration of 1-20% by weight.  
   
   
       21 . The method of  claim 13 , wherein the disorder is a skin disorder selected from the group consisting of psoriasis, acne, rosacea, and eczema.  
   
   
       22 . The method of  claim 13 , wherein the disorder is psoriasis.  
   
   
       23 . A pharmaceutically acceptable carbazole formulation, comprising an effective amount of purified carbazole, or a derivative thereof, having the general formula:  
     
       
         
         
             
             
         
       
       wherein, R1-R9 can be a hydrogen atom, halogen atom, alkyl group, trihaloalkyl group, alkenyl group, alkynyl group, cycloalkyl group, cycloalkenyl group, amino group, aryl group, heteroaryl group, heteroalicyclic group, hydroxyl group, alkoxy group, cycloalkoxy group, aryloxy group, heteroaryloxy group, heteroalicycloxy group, thiohydroxy group, thioalkyoxy group, thiocycloalkoxy group, thioheteraryloxy group, thioheteralicycloxy group, cyano group, carbamyl group, C—O-carbamyl group, N-carbamyl group, O-thiocarbamyl group, N-thiocarbamyl group, silyl group, phosphonyl group, C-carboxy group, O-carboxy group, N-amido group, C-amido group, sulfinyl group sulfonyl group S-sulfonamido group, N-sulfonamido group, trihalomethanesulfonyl group, guanyl group, guanidine group, trihalomethanesulfonamido group; and  
       a pharmaceutically acceptable carrier.  
     
   
   
       24 . The formulation of  claim 23 , wherein R1-R9 are all hydrogen.  
   
   
       25 . The formulation of  claim 23 , wherein the carbazole is hydroxylated, halogenated, or oxidized.  
   
   
       26 . The formulation of  claim 23 , wherein the carbazole is carbamazepine.  
   
   
       27 . The formulation of  claim 25 , wherein the carbazole is selected from the group consisting of 2-hydroxy-carbazole, 3-hydroxy-carbazole, 4-hydroxy-carbazole, 2,2-hydroxy-carbazole, and 2,4-hydroxycarbazole.  
   
   
       28 . The formulation of  claim 23 , wherein the carrier is selected from the group consisting of ointments, gels, lotions, powders, sprays, foams, shampoos, and pharmaceutically acceptable solutions for administration to the skin.  
   
   
       29 . The formulation of  claim 23 , wherein the carbazole is at a concentration of 1-20% drug by weight of pharmaceutically acceptable carrier.