Retinoids and use thereof

Abstract

The present invention provides new retinoid compounds and uses of the compounds in humans and animals for non-neoplastic dermal or inflammatory conditions or disorders.

1 . A method for treating, preventing or lessening the severity of a non-neoplastic skin condition or disorder in a patient in need thereof, comprising the step of administering to said patient a compound, or a composition comprising the compound, said compound having the chemical formula selected from Formula I and Formula II, below: 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is H, CF 3  or a C1-C5 or greater branched or straight chain alkyl group; 
 R 2  is H, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted cycloalkyl group, or 
 R1 and R2 collectively form a substituted or unsubstituted fused aryl group; and 
 R 3  is one or more groups comprising, independently, H, F, diflouro, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, a substituted or unsubstituted cycloalkyl group; 
 R 6  and R 7  are, independently, H, CF 3 , a C1-C15 branched or straight chain alkyl group, or a substituted or unsubstituted cycloalkyl group; 
 R H  is H, or a C1-C15 branched or straight chain alkyl group. 
 n is from 0 to 3; 
 wherein one or more carbons in the ring structures of Formula I or II can optionally be replaced with a heteroatom; 
 or a pharmaceutically acceptable salt or isomer thereof. 
 
     
     
         2 . The method of  claim 1  wherein the compound has the chemical formula of Formula III, below: 
       
         
           
           
               
               
           
         
       
       wherein,
 R 3  is one or more groups comprising, independently, H, F, diflouro, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, a substituted or unsubstituted cycloalkyl group; 
 R 6  and R 7  are, independently, H, CF 3 , a C1-C15 branched or straight chain alkyl group, or a substituted or unsubstituted cycloalkyl group; 
 R 9  is one or more groups comprising, independently, H, F, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted cycloalkyl group; 
 R 11  is H, or a C1-C15 branched or straight chain alkyl group. n is from 0 to 3; 
 wherein one or more carbons in the fused ring structure can optionally be replaced with a heteroatom; 
 or a pharmaceutically acceptable salt or isomer thereof. 
 
     
     
         3 . The method of  claim 2  wherein the compound has the chemical formula shown as Formula IV: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 1  wherein the skin condition or disorder is selected from dermatological afflictions associated with excessive skin sebum production, and/or cell differentiation and/or proliferation disorders, and/or keratinization disorders and/or skin pigmentation disorders, and/or skin inflammatory disorders. 
     
     
         5 . The method of  claim 1  wherein the skin condition or disorder is selected from the dermatological afflictions associated photo-induced skin damage or chronological skin aging. 
     
     
         6 . The method of  claim 4  wherein the skin condition or disorder is selected from the group consisting of acne vulgaris, psoriasis, actinic keratosis, rosacea, seborrheic dermatitis, actinic lentigines, eczema, warts, keratosis, xerosis, icthyosis, lichen, keratoderma, folliculitis, vitiligo and melasma. 
     
     
         7 . The method of  claim 4  wherein the skin condition is acne vulgaris. 
     
     
         8 . The method of  claim 4  wherein the skin condition is psoriasis. 
     
     
         9 . The method of  claim 4  wherein the skin condition is actinic keratosis. 
     
     
         10 . A pharmaceutically acceptable dermal composition for treating, preventing or ameliorating a non-neoplastic dermal condition, said composition comprising a vehicle or carrier pharmaceutically acceptable for dermal application and a compound having the chemical formula selected from Formula I and Formula II: 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is H, CF 3  or a C1-C5 or greater branched or straight chain alkyl group; 
 R 2  is H, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted cycloalkyl group, or 
 R1 and R2 collectively form a substituted or unsubstituted fused aryl group; and 
 R 3  is one or more groups comprising, independently, H, F, difluoro, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, a substituted or unsubstituted cycloalkyl group; 
 R 6  and R 7  are, independently, H, CF 3 , a C1-C15 branched or straight chain alkyl group, or a substituted or unsubstituted cycloalkyl group; 
 R H  is H, or a C1-C15 branched or straight chain alkyl group. 
 n is from 0 to 3; 
 wherein one or more carbons in the ring structures of Formula I or II can optionally be replaced with a heteroatom; 
 
       or a pharmaceutically acceptable salt or isomer thereof. 
     
     
         11 . The composition of  claim 10  wherein the compound has the chemical formula shown as Formula III: 
       
         
           
           
               
               
           
         
       
       wherein,
 R 3  is one or more groups comprising, independently, H, F, diflouro, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, a substituted or unsubstituted cycloalkyl group; 
 R 6  and R 7  are, independently, H, CF 3 , a C1-C15 branched or straight chain alkyl group, or a substituted or unsubstituted cycloalkyl group; 
 R 9  is one or more groups comprising, independently, H, CF 3 , a C1-C15 branched or straight chain alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted cycloalkyl group; 
 R H  is H, or a C1-C15 branched or straight chain alkyl group. n is from 0 to 3; 
 wherein one or more carbons in the fused ring structure can optionally be replaced with a heteroatom; 
 or a pharmaceutically acceptable salt or isomer thereof. 
 
     
     
         12 . The composition of  claim 11  wherein the compound has the chemical formula shown as Formula IV, below: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The composition of  claim 10 , wherein the composition is formulated for topical administration. 
     
     
         14 . The composition of  claim 10  comprising at least two active ingredients. 
     
     
         15 . The composition of  claim 14 , wherein at least one of the active ingredients is a sunscreen. 
     
     
         16 . The composition of  claim 14  comprising at least two retinoid compounds. 
     
     
         17 . The composition of  claim 14  comprising at least one non-retinoid compound. 
     
     
         18 . The composition of  claim 16  further comprising a non-retinoid compound. 
     
     
         19 . The composition of  claim 10  wherein said compound is provided at a concentration of about 0.01% to about 10% (w/w). 
     
     
         20 . The composition of  claim 19  wherein the concentration of the compound is about 0.1% to about 3.0% (w/w). 
     
     
         21 . The composition of  claim 10 , wherein the composition is formulated for oral administration. 
     
     
         22 . The composition of  claim 21  wherein the composition is in the form of a tablet. 
     
     
         23 . The composition of  claim 21  wherein the composition is in the form of a capsule. 
     
     
         24 . The composition of  claim 21  comprising at least two active ingredients. 
     
     
         25 . The composition of  claim 24  comprising at least two retinoid compounds. 
     
     
         26 . The composition of  claim 24  comprising at least one non-retinoid compound. 
     
     
         27 . The composition of  claim 21  wherein the compound is administered at a dose of about 0.01 mg/Kg to about 300 mg/kg of body weight. 
     
     
         28 . The composition of  claim 27  wherein the compound is administered at a dose of about 0.1 mg/Kg to about 30 mg/kg of body weight.