High penetration prodrug compositions of retinoids and retinoids-related compounds

A method for treating a retinoids-treatable condition in a biological subject, comprising administrating to the biological subject a therapeutically effective amount of a pharmaceutical composition comprising a high penetration prodrug of Structure L-1:

• or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:
• F comprises a moiety of a retinoid compound, having a structure selected from Structure F5, Structure F16, and Structure F23:
• wherein:
• X1-X5 are independently selected from H, OH, Cl, Br, F, I, substituted and unsubstituted alkyl, substituted and unsubstituted perfluoroalkyl, and substituted and unsubstituted alkyloxy;
• R4 is selected from H, OH, Cl, Br, F, I, substituted and unsubstituted alkyl, substituted and unsubstituted alkyloxy, and substituted and unsubstituted perfluoroalkyl;
• R5 is selected from H, OH, Cl, Br, F, I, substituted and unsubstituted alkyl, substituted and unsubstituted alkyloxy, and substituted and unsubstituted perfluoroalkyl;
• T is selected from Structure Na, Structure Nb, Structure Nc, Structure Ne, Structure Ng, Structure Nh, and Structure Nm:
• wherein:
• R11 and R12 in Structure Na are same or different and each independently selected from H, substituted and unsubstituted alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl;
• R11, R12 and R13 in Structure Nb, Structure Nc, Structure Ng or Structure Nh are each independently substituted or unsubstituted alkylene;
• R11 and R13 in Structure Ne and Structure Nm are each independently substituted or unsubstituted methine, and R12 is substituted or unsubstituted alkylene;
• each R14 is selected from H, substituted and unsubstituted alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl;
• L1 is selected from a bond, O, S, —N(L3)—, —N(L3)-CH2—O—, —N(L3)-CH2—N(L5)—, —O—CH2—O—, —O—CH(L3)-O, and —S—CH(L3)-O—;
• L2 is selected from a bond, O, S, —N(L3)—, —N(L3)-CH2—O—, —N(L3)-CH2—N(L5)—, —O—CH2—O—, —O—CH(L3)-O, —S—CH(L3)-O—, —O-L5-, —S-L5-, —N(L3)-L5-, and L5, when T is Structure Nb, Structure Nc, or Structure Ne;
• or L2 is selected from —O-L5-, —S-L5-, —N(L3)-L5-, and L5, when T is Structure Na or Structure Ng;
• or L2 is selected from a bond, —O-L5-, —S-L5-, —N(L3)-L5-, and L5, when T is Structure Nh or Structure Nm;
• provided that L1 is not a bond when L2 is a bond or L5;
• L4 is C(═O) or C(═S);
• each L3 is independently selected from H, substituted and unsubstituted alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl;
• and
• each L5 is independently selected from substituted and unsubstituted alkylene, substituted and unsubstituted cycloalkylene, substituted and unsubstituted heterocycloalkylene, substituted and unsubstituted arylene, and substituted and unsubstituted heteroarylene.