Methods of treating retinitis pigmentosa
The present invention relates to methods of treating retinitis pigmentosa using β-turn peptidomimetic cyclic compounds or derivatives thereof. The β-turn peptidomimetic cyclic compounds can be used alone, in combination and/or in conjunction with one or more other compounds, molecules or drugs useful in treating retinitis pigmentosa.
1. A method of treating retinitis pigmentosa in a subject in need thereof comprising administering to said subject an effective amount of a β-turn peptidomimetic cyclic compound, wherein said β-turn peptidomimetic cyclic compound is represented by structural Formula (I):
wherein R 1 and R 3 are independently selected from hydrogen, C 1 to C 6 alkyl, aryl, or amino acid side chain substituent found in the twenty protein-amino acids; R 2 and R 4 are independently hydrogen or alkyl; or R 1 and R 2 together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group; or R 3 and R 4 together with the carbon atom to which they are attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group; R 5 and R 6 are hydrogen or C 1 to C 6 alkyl; Y is hydrogen or one or two aromatic substituents; X is selected from O, N, S, P, Se, C, alkylene of 1 to 6 carbon atoms, SO, SO 2 or NH; n is 0, 1, 2, 3, 4 or 5; and LINKER selected from the group consisting of: NH 2 , OH, SH, COOH, CH 3 CO, CHO, and NH—CH 2 —COOH.
2. The method of claim 1 , wherein X is O, S or NH, R 1 , R 3 , R 5 and R 6 are each hydrogen atoms and the macrocyclic ring has 14, 15 or 16 ring atoms.
3. The method of claim 1 , wherein R 1 and R 3 are derived from a sequence of different amino acids side chains.
4. The method of claim 3 , wherein X is O, S or NH.
5. The method of claim 1 , wherein said β-turn peptidomimetic cyclic compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
6. A method of treating retinitis pigmentosa in a subject in need thereof comprising administering to said subject an effective amount of a β-turn peptidomimetic cyclic compound represented by Formula D3:
or a pharmaceutically acceptable salt thereof.
7. A method of treating retinitis pigmentosa in a subject in need thereof comprising administering to said subject an effective amount of a β-turn peptidomimetic cyclic compound represented by Formula 3Ae:
or a pharmaceutically acceptable salt thereof.
8. A method of treating retinitis pigmentosa in a subject in need thereof comprising administering to said subject an effective amount of a β-turn peptidomimetic cyclic compound represented by Formula 3Ak:
or a pharmaceutically acceptable salt thereof.