Series of skin whitening (lightening) compounds
The present invention is directed to inhibitors of tyrosinase, pharmaceutical compositions comprising such tyrosinase inhibitors, and methods of making and using the same. Specifically, included in the present invention are compositions of matter comprised of at least one 2,4-dihydroxybenzene analog, which inhibit the activity of tyrosinase and which inhibit the overproduction of melanin.
1. A compound of Formula III:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or C 1 -C 10 alkyl; and
R 2 is 4-hydroxyphen-1-yl, 4-methoxyphen-1-yl, 2,4-dimethoxyphen-1-yl, 3,5-dimethoxyphen-1-yl, 2,4-dimethoxy-3-methylphen-1-yl, 2,4,6-trimethoxyphen-1-yl, furan-3-yl; tetrahydrofuran-3-yl, furan-2-yl, tetrahydrofuran-2-yl, 5-ethylfuran-2-yl or pyridin-3-yl.
2. The compound of claim 1 , wherein R 1 is H.
3. The compound of claim 1 , wherein R 1 is methyl.
4. The compound of claim 1 , wherein the compound is 4-(4-hydroxyphenethyl)benzene-1,3-diol (13), 4-(4-methoxyphenethyl)benzene-1,3-diol (14), 4-(2,4-dimethoxyphenethyl)benzene-1,3-diol (17), 4-(3,5-dimethoxyphenethyl)benzene-1,3-diol (18), 4-(2,4-dimethoxy-3-methylphenethyl)benzene-1,3-diol (19), 4-(2,4,6-trimethoxyphenethyl)benzene-1,3-diol (20), 4-(2-(furan-3-yl)ethyl)benzene-1,3-diol (22), 4-(2-(tetrahydrofuran-3-yl)ethyl)benzene-1,3-diol (23), 4-(2-(furan-2-yl)ethyl)benzene-1,3-diol (24), 4-(2-(tetrahydrofuran-2-yl)ethyl)benzene-1,3-diol (25), 4-(2-(5-ethylfuran-2-yl)ethyl)benzene-1,3-diol (26) or 4-(2-(pyridin-3-yl)ethyl)benzene-1,3-diol (27).
5. A composition comprising the compound of claim 1 and a pharmaceutically or cosmetically acceptable carrier.
6. The composition of claim 5 , wherein the compound is 4-(4-hydroxyphenethyl)benzene-1,3-diol (13), 4-(4-methoxyphenethyl)benzene-1,3-diol (14), 4-(2,4-dimethoxyphenethyl)benzene-1,3-diol (17), 4-(3,5-dimethoxyphenethyl)benzene-1,3-diol (18), 4-(2,4-dimethoxy-3-methylphenethyl)benzene-1,3-diol (19), 4-(2,4,6-trimethoxyphenethyl)benzene-1,3-diol (20), 4-(2-(furan-3-yl)ethyl)benzene-1,3-diol (22), 4-(2-(tetrahydrofuran-3-yl)ethyl)benzene-1,3-diol (23), 4-(2-(furan-2-yl)ethyl)benzene-1,3-diol (24), 4-(2-(tetrahydrofuran-2-yl)ethyl)benzene-1,3-diol (25), 4-(2-(5-ethylfuran-2-yl)ethyl)benzene-1,3-diol (26) or 4-(2-(pyridin-3-yl)ethyl)benzene-1,3-diol (27) or a pharmaceutically acceptable salt thereof.