High penetration compositions and their applications
High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.
1. A compound of Structure P4-3:
wherein:
T is selected from the group consisting of
L 41 is selected from the group consisting of N and N-L 3 ;
wherein L 3 is selected from the group consisting of C 1 -C 12 alkylene, C 3 -C 12 cycloalkylene, C 3 -C 12 heterocycloalkylene, arylene, heteroarylene, C 1 -C 12 alkoxylene, C 1 -C 12 alkylenethio, C 1 -C 12 perfluoroalkylene, and C 1 -C 12 alkylene halide;
each Y1-Y 11 is independently selected from the group consisting of H, CI, F, Br, I, CN, CH 3 C═C, CF 3 , CH 3 , CF 3 CF 2 , CH 3 CH 2 , CH 3 CH 2 CH 2 , (CH 3 ) 2 CH, (CH 3 ) 2 CHCH 2 , CH 3 CH 2 CH(CH 3 ), (CH 3 ) 3 C, C 5 H11, CH 3 CO, CH 3 CH 2 CO, CH 3 OC(═O), CH 3 CH 2 OC(═O), CH 3 COO, CH 3 COS, CH 3 O, HO, CF 3 CH 2 SCH 2 , CHCI 2 , CH 3 S, HS, CH 3 OCH 2 CH 2 , C 2 H 5 OCONH, CH 3 OCONH, CH 3 SO 2 , CH 3 SO, NH 2 SO 2 , C 6 H 5 CH 2 , NH 2 , cyclobutyl, cyclopropyl, 4-chlorophenyl, 4-fluorophenyl, CH 2 ═CH, CH 2 ═CHCH 2 , CH 3 CH═CH, and NO 2 ;
R is selected from the group consisting of C 1 -C 12 alkylene, C 3 -C 12 cycloalkylene, C 3 -C 12 heterocycloalkylene, arylene, heteroarylene, C 1 -C 12 alkoxylene, C 1 -C 12 alkylenethio, C 1 -C 12 perfluoroalkylene, and C 1 -C 12 alkylene halide;
each R 1 and R 2 is independently selected from the group consisting of H, C 1 -C 12 alkyl, C 3 -C 12 cycloalkyl, C 3 -C 12 heterocycloalkyl, aryl, heteroaryl, C 1 -C 12 alkoxyl, C 1 -C 12 alkylthio, C 1 -C 12 alkylamino, C 1 -C 12 perfluoroalkyl, and C 1 -C 12 alkyl halide;
each R 11 -R 13 is independently selected from the group consisting of nothing, C 1 -C 12 alkylene, C 3 -C 12 cycloalkylene, C 3 -C 12 heterocycloalkylene, arylene, heteroarylene, C 1 -C 12 alkoxylene, C 1 -C 12 alkylenethio, C 1 -C 12 alkyleneamino, C 1 -C 12 perfluoroalkylene, and C 1 -C 12 alkylene halide; and
HA is a pharmaceutically acceptable acid.
2. The compound according to claim 1 , wherein T is T-1.
3. The compound according to claim 1 , wherein T is T-2.
4. The compound according to claim 1 , wherein T is T-4.
5. A composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.