RU2015141118A - S1P RECEPTOR MODULATORS FOR THE TREATMENT OF MULTIPLE SCLEROSIS - Google Patents

Claims (23)

1. The use of an S1P receptor modulator, for example, a compound of formulas I-IXb, as described above, for the manufacture of a medicament for the prophylaxis, suppression or treatment of neoangiogenesis associated with a demyelinating disease, for example, multiple sclerosis. 2. The use of an S1P receptor modulator, for example, a compound of formulas I-IXb, as described above, for the manufacture of a medicament for the prophylaxis, suppression or treatment of relapsing-remitting multiple sclerosis (PP-MS). 3. The use of claim 1 or 2, wherein the S1P receptor modulator comprises a group of formula X:

where Z is H, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, phenyl, phenyl substituted with OH, C ₁ -C ₆ alkyl containing from 1 to 3 substituents selected from a group consisting of halogen, C ₃ -C ₈ cycloalkyl, phenyl and phenyl substituted with an OH or CH ₂ -R _4z group, where R _4z is OH, acyloxy or a residue of formula (a)

where Z ₁ means a single bond or O, preferably O, R _5z and R _6z each independently mean H or C ₁ -C ₄ alkyl, optionally substituted with 1, 2 or 3 halogen atoms, R _1z is OH, acyloxy or a residue of formula (a), and R _2z and R _{3z are} each independently H, C ₁ -C ₄ alkyl or acyl. 4. The use according to claim 1 or 2, where the drug is administered together, for example, simultaneously or sequentially, with a VEGF receptor antagonist, for example, as defined above. 5. The use according to claim 1 or 2, wherein the S1P receptor modulator or agonist is 2-amino-2- [2- (4-octylphenyl) ethyl] propan-1,3-diol, 2-amino-2- [4- (3-besyloxyphenoxy) -2-chlorophenyl] ethyl-1,3-propanediol or 1- {4- [1- (4-cyclohexyl-3-trifluoromethylbenzyloxyimino) ethyl] -2-ethylbenzyl} azetidine-3-carboxylic acid form or in the form of a pharmaceutically acceptable salt. 6. The use of claim 5, wherein the S1P receptor modulator is 2-amino-2- [2- (4-octylphenyl) ethyl] propane-1,3-diol in free form or in the form of a pharmaceutically acceptable salt. 7. A pharmaceutical composition for use according to any one of the preceding claims, comprising an S1P receptor modulator, for example, a compound of formulas I-IXb, as defined above, in admixture with one or more pharmaceutically acceptable diluents or carriers. 8. The pharmaceutical composition according to claim 7, wherein the S1P receptor modulator or agonist is 2-amino-2- [2- (4-octylphenyl) ethyl] propan-1,3-diol, 2-amino-2- [4- ( 3-becyloxyphenoxy) -2-chlorophenyl] ethyl-1,3-propanediol or 1- {4- [1- (4-cyclohexyl-3-trifluoromethylbenzyloxyimino) ethyl] -2-ethylbenzyl} azetidine-3-carboxylic acid in free form or in the form of a pharmaceutically acceptable salt. 9. The pharmaceutical composition of claim 8, wherein the S1P receptor modulator is 2-amino-2- [2- (4-octylphenyl) ethyl] propan-1,3-diol in free form or in the form of a pharmaceutically acceptable salt. 10. A pharmaceutical combination, for example, a kit comprising a) a first agent, which is an S1P receptor modulator, for example, a compound of formulas I-IXb, as defined above, in free form or in the form of a pharmaceutically acceptable salt, and b) a VEGF receptor antagonist, for example as defined above. 11. The pharmaceutical combination of claim 10, wherein the S1P receptor modulator or agonist is 2-amino-2- [2- (4-octylphenyl) ethyl] propan-1,3-diol, 2-amino-2- [4- ( 3-becyloxyphenoxy) -2-chlorophenyl] ethyl-1,3-propanediol or 1- {4- [1- (4-cyclohexyl-3-trifluoromethylbenzyloxyimino) ethyl] -2-ethylbenzyl} azetidine-3-carboxylic acid in free form or in the form of a pharmaceutically acceptable salt. 12. The pharmaceutical combination of claim 11, wherein the S1P receptor modulator is 2-amino-2- [2- (4-octylphenyl) ethyl] propan-1,3-diol in free form or in the form of a pharmaceutically acceptable salt. 13. A method for preventing, suppressing, or treating neoangiogenesis associated with a demyelinating disease, for example, multiple sclerosis, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an S1P receptor modulator, for example, a compound of formulas I-IXb as defined above . 14. A method for the prevention, suppression, or treatment of PP-MS in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an S1P receptor modulator, for example, a compound of formulas I-IXb, as defined above. 15. The method of claim 13 or 14, wherein the S1P receptor modulator is administered periodically. 16. The method of claim 13 or 14, wherein the S1P receptor modulator or agonist is 2-amino-2- [2- (4-octylphenyl) ethyl] propan-1,3-diol, 2-amino-2- [4- (3-besyloxyphenoxy) -2-chlorophenyl] ethyl-1,3-propanediol or 1- {4- [1- (4-cyclohexyl-3-trifluoromethylbenzyloxyimino) ethyl] -2-ethylbenzyl} azetidine-3-carboxylic acid form or in the form of a pharmaceutically acceptable salt. 17. The method of claim 16, wherein the S1P receptor modulator is 2-amino-2- [2- (4-octylphenyl) ethyl] propane-1,3-diol in free form or in the form of a pharmaceutically acceptable salt.