High penetration prodrug compositions and pharmaceutical composition thereof for treatment of pulmonary conditions

A topical pharmaceutical formulation comprising a pharmaceutically acceptable carrier and a compound of Structure LRA-1:

• wherein
• X5 is selected from nothing, C(═O), OC(═O), CH2, O, and NR5;
• Y1, Y2, Y3, Y4, Y5, Y6, Y7, and Y8 are each independently selected from H, OH, OW, OC(═O)W, OC(═O)CH3, CH2OR6, CH2C(═O)OR5, OR6, CF3, OCF3, CH2(CH2)nOR6, F, Br, I, Cl, C(═O)R5, (CH3)2C(OR6)—, CH3CH(OH)—, (CH3)2CH—, CH3CH2—, substituted and unsubstituted C1-C30 alkyl, substituted and unsubstituted C1-C30 alkoxyl, and substituted and unsubstituted C1-C30 alkylamino, wherein n is an integer selected from 1 to 10;
• R5 is selected from H, OR6, CH2CH2OR6, CH2CH2N(CH3)2, CH2CH2N(CH2CH3)2, Cl, F, Br, I, substituted and unsubstituted C1-C30 alkyl, substituted and unsubstituted C3-C30 cycloalkyl, substituted and unsubstituted C3-C30 heterocycloalkyl, substituted and unsubstituted C1-C30 alkyloxyl, substituted and unsubstituted C3-C30 cycloalkyloxyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted C1-C30 alkylcarbonyl, substituted and unsubstituted C1-C30 alkylamino, L1-L4-L2-W, and C—(═O)-W;
• R6 is selected from H, F, Cl, Br, I, C(═O)R5, substituted and unsubstituted C1-C30 alkyl, substituted and unsubstituted C3-C30 cycloalkyl, substituted and unsubstituted C3-C30 heterocycloalkyl, substituted and unsubstituted C2-C30 alkenyl, substituted and unsubstituted C2-C30 alkynyl, substituted and unsubstituted C1-C30 alkyloxyl, substituted and unsubstituted C3-C30 cycloalkyloxyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, L1-L4-L2-W, and C—(═O)-W;
• R is selected from nothing, CH2C(═O)OR6, substituted and unsubstituted C1-C30 alkylene, substituted and unsubstituted C3-C30 cycloalkylene, substituted and unsubstituted C3-C30 heterocycloalkylene, substituted and unsubstituted C1-C30 alkoxylene, substituted and unsubstituted C2-C30 alkenylene, substituted and unsubstituted C2-C30 alkynylene, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl, wherein any CH2 in R may be further replaced with O, S, or NR6;
• R1 and R2 are each independently selected from H, substituted and unsubstituted C1-C30 alkyl, substituted and unsubstituted C3-C30 cycloalkyl, substituted and unsubstituted C3-C30 heterocycloalkyl, substituted and unsubstituted C1-C30 alkyloxyl, substituted and unsubstituted C2-C30 alkenyl, substituted and unsubstituted C2-C30 alkynyl, substituted and unsubstituted aryl and substituted and unsubstituted heteroaryl residues, wherein any CH2 group(s) may be replaced with O, S, or NH;
• R11 and R12 are each independently selected from nothing, H, CH2C(═O)OR11, substituted and unsubstituted C1-C30 alkylene, substituted and unsubstituted C3-C30 cycloalkylene, substituted and unsubstituted C3-C30 heterocycloalkylene, substituted and unsubstituted C1-C30 alkoxylene, substituted and unsubstituted C2-C30 alkenylene, substituted and unsubstituted C2-C30 alkynylene, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl, wherein any CH2 group(s) may be replaced with O, S, or NH;
• L1 and L2 are each independently selected from nothing, O, —O-L3-, —N(L3)-, —N(L3)-CH2—O, —N(L3)-CH2—N(L5)-, —O—CH2—O—, and —O—CH(L3)-O, wherein for each of L1 and L2, each of L3 and L5 is independently selected from nothing, H, substituted and unsubstituted C1-C30 alkyl, substituted and unsubstituted C3-C30 cycloalkyl, substituted and unsubstituted C3-C30 heterocycloalkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted C1-C30 alkoxyl, substituted and unsubstituted C1-C30 alkylamino, wherein any carbon or hydrogen may be further independently replaced with O, S, or NL3;
• L4 is selected from nothing and C═O;
• W is selected from Structure W-1 and Structure W-2:
• HA is selected from nothing, hydrochloride, hydrobromide, hydroiodide, nitric acid, sulfic acid, bisulfic acid, phosphoric acid, phosphorous acid, phosphonic acid, isonicotinic acid, acetic acid, lactic acid, salicylic acid, citric acid, tartaric acid, pantothenic acid, bitartaric acid, ascorbic acid, succinic acid, maleic acid, or any other pharmaceutically acceptable acid.