RU2006125744A - Применение агонистов рецептора сфингозин-1-фосфата (s1p) для лечения дегенеративных заболеваний головного мозга - Google Patents
Применение агонистов рецептора сфингозин-1-фосфата (s1p) для лечения дегенеративных заболеваний головного мозга Download PDFInfo
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- 229940044601 receptor agonist Drugs 0.000 title claims abstract 6
- 239000000018 receptor agonist Substances 0.000 title claims abstract 6
- 210000004556 brain Anatomy 0.000 title claims abstract 4
- 229910019142 PO4 Inorganic materials 0.000 title claims 2
- 239000010452 phosphate Substances 0.000 title claims 2
- 230000003412 degenerative effect Effects 0.000 title 1
- 201000010099 disease Diseases 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title 1
- 206010012289 Dementia Diseases 0.000 claims abstract 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract 6
- 230000000750 progressive effect Effects 0.000 claims abstract 6
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 claims abstract 5
- 229940124118 AMPA receptor agonist Drugs 0.000 claims abstract 2
- 239000000774 AMPA receptor agonist Substances 0.000 claims abstract 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract 2
- 239000003795 chemical substances by application Substances 0.000 claims abstract 2
- 239000002664 nootropic agent Substances 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims 8
- 229940121846 Sphingosine 1-phosphate receptor agonist Drugs 0.000 claims 7
- 125000000217 alkyl group Chemical group 0.000 claims 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 6
- 208000027866 inflammatory disease Diseases 0.000 claims 6
- -1 carboxyloxy hydroxy Chemical group 0.000 claims 5
- 125000002252 acyl group Chemical group 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims 3
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims 3
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 claims 3
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 claims 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 201000004559 cerebral degeneration Diseases 0.000 claims 3
- 230000001149 cognitive effect Effects 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical group 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims 3
- 125000004442 acylamino group Chemical group 0.000 claims 2
- 125000004423 acyloxy group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 125000004414 alkyl thio group Chemical group 0.000 claims 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 230000000202 analgesic effect Effects 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000011260 co-administration Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical group CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000001777 nootropic effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims 1
- 125000002071 phenylalkoxy group Chemical group 0.000 claims 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
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Claims (10)
1. Применение агониста рецептора сфингозин-1-фосфата (S1P) или его фармацевтически приемлемой соли для приготовления лекарственного средства, предназначенного для лечения прогрессирующей деменции или дегенерации головного мозга.
2. Применение агониста рецептора сфингозин-1-фосфата или его фармацевтически приемлемой соли для приготовления лекарственного средства, предназначенного для лечения связанных с β-амилоидом воспалительных заболеваний или нарушений.
3. Применение агониста рецептора сфингозин-1-фосфата (S1P) или его фармацевтически приемлемой соли для приготовления лекарственного средства, предназначенного для снижения или ингибирования утраты когнитивных способностей.
4. Фармацевтическая композиция, предназначенная для применения при лечении прогрессирующей деменции или дегенерации головного мозга, связанных с β-амилоидом воспалительных заболеваний или нарушений или снижения или ингибирования утраты когнитивных способностей, содержащая агонист рецептора сфингозин-1-фосфата или его фармацевтически приемлемую соль в сочетании с одним или несколькими фармацевтически приемлемыми разбавителями или носителями.
5. Фармацевтическая комбинация, содержащая а) первый агент, представляющий собой агонист S1P-рецептора или его фармацевтически приемлемую соль, и б) коагент, который можно применять для облегчения или лечения дегенеративных заболеваний головного мозга или прогрессирующей деменции.
6. Комбинация по п.5, в которой коагент б), выбран из агониста АМРА-рецептора, ноотропического или противовоспалительного агента или болеутоляющего средства.
7. Способ лечения прогрессирующей деменции или дегенерации головного мозга или связанных с β-амилоидом воспалительных заболеваний или нарушений, или снижения или ингибирования утраты когнитивных способностей у индивидуума, который нуждается в этом, заключающийся в том, что индивидууму вводят терапевтически эффективное количество агониста рецептора сфингозин-1-фосфата (S1P) или его фармацевтически приемлемой соли.
8. Способ по п.7, заключающийся в том, что осуществляют совместное введение, например одновременное или последовательное, с коагентом б), который можно применять для облегчения или лечения дегенеративных заболеваний головного мозга или прогрессирующей деменции.
9. Способ, композиция, комбинация или применение по одному из предыдущих пунктов, в которых агонист S1P-рецептора представляет собой соединение формулы I
в которой R1 обозначает прямую или разветвленную углеродную C12-С22цепь,
где в цепи может находиться связь или гетероатом, выбранные из группы, включающей двойную связь, тройную связь, О, S, NR6, где R6 обозначает Н, алкил, аралкил, ацил или алкоксикарбонил и карбонил, и/или
где может находиться в качестве заместителя алкоксигруппа, алкенилоксигруппа, алкинилоксигруппа, аралкилоксигруппа, ацил, алкиламиногруппа, алкилтиогруппа, ациламиногруппа, алкоксикарбонил, алкоксикарбониламиногруппа, ацилоксигруппа, алкилкарбамоил, нитрогруппа, галоген, аминогруппа, гидроксииминогруппа, гидроксигруппа или карбоксигруппа; или
R1 обозначает
фенилалкил, в котором алкил обозначает прямую или разветвленную углеродную C6-C20цепь; или
фенилалкил, в котором алкил обозначает прямую или разветвленную углеродную C1-C30цепь, где фенилалкил замещен
прямой или разветвленной углеродной C6-C20цепью, необязательно замещенной галогеном,
прямой или разветвленной углеродной C6-C20алкоксигруппой, необязательно замещенной галогеном,
прямой или разветвленной C6-C20алкенилоксигруппой,
фенилалкоксигруппой, галофенилалкоксигруппой, фенилалкоксиалкилом, феноксиалкоксигруппой или феноксиалкилом,
циклоалкилалкилом, замещенным C6-C20алкилом,
гетероарилалкилом, замещенным C6-C20алкилом,
гетероциклическим C6-C20алкилом или
гетероциклическим алкилом, замещенным C2-C20алкилом,
и где алкильный радикал может иметь
в углеродной цепи связь или гетероатом, выбранные из двойной связи, тройной связи, О, S, сульфинила, сульфонила или NR6, где R6 имеет указанные выше значения, и
в качестве заместителя алкоксигруппу, алкенилоксигруппу, алкинилоксигруппу, аралкилоксигруппу, ацил, алкиламиногруппу, алкилтиогруппу, ациламиногруппу, алкоксикарбонил, алкоксикарбониламиногруппу, ацилоксигруппу, алкилкарбамоил, нитрогруппу, галоген, аминогруппу, гидроксигруппу или карбоксигруппу, и R2, R3, R4 и R5, каждый независимо друг от друга, обозначает Н, C1-C4алкил или ацил,
или его фармацевтически приемлемую соль.
10. Способ, композиция, комбинация или применение по п.9, в которых агонист S1P-рецептора представляет собой 2-амино-2-[2-(4-октилфенил)этил]пропан-1,3-диол в свободной форме или в форме фармацевтически приемлемой соли.
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| GB0329498.0 | 2003-12-19 |
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