RU2006135541A - Производные аминокислот - Google Patents
Производные аминокислот Download PDFInfo
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- RU2006135541A RU2006135541A RU2006135541/04A RU2006135541A RU2006135541A RU 2006135541 A RU2006135541 A RU 2006135541A RU 2006135541/04 A RU2006135541/04 A RU 2006135541/04A RU 2006135541 A RU2006135541 A RU 2006135541A RU 2006135541 A RU2006135541 A RU 2006135541A
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- alkyl
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- 150000003862 amino acid derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 9
- 150000003839 salts Chemical group 0.000 claims 8
- 125000001153 fluoro group Chemical group F* 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 208000024827 Alzheimer disease Diseases 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 125000006239 protecting group Chemical group 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 2
- 208000032456 Hemorrhagic Shock Diseases 0.000 claims 2
- 208000009525 Myocarditis Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010049771 Shock haemorrhagic Diseases 0.000 claims 2
- 206010044541 Traumatic shock Diseases 0.000 claims 2
- 230000033115 angiogenesis Effects 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 230000006378 damage Effects 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 208000024908 graft versus host disease Diseases 0.000 claims 2
- 208000006454 hepatitis Diseases 0.000 claims 2
- 231100000283 hepatitis Toxicity 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 208000028867 ischemia Diseases 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 230000010410 reperfusion Effects 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- HBEUHDJEXSWDPB-GOSISDBHSA-N (2r)-2-amino-4-(4-heptoxyphenyl)-2-methylbutanoic acid Chemical compound CCCCCCCOC1=CC=C(CC[C@@](C)(N)C(O)=O)C=C1 HBEUHDJEXSWDPB-GOSISDBHSA-N 0.000 claims 1
- VBYQVUKISPYLQE-LJQANCHMSA-N (3r)-3-amino-5-(4-heptoxyphenyl)-3-methylpentanoic acid Chemical compound CCCCCCCOC1=CC=C(CC[C@@](C)(N)CC(O)=O)C=C1 VBYQVUKISPYLQE-LJQANCHMSA-N 0.000 claims 1
- DGAGMTJLEUOLJC-HXUWFJFHSA-N (4r)-4-amino-6-(4-heptoxyphenyl)-4-methylhexanoic acid Chemical compound CCCCCCCOC1=CC=C(CC[C@@](C)(N)CCC(O)=O)C=C1 DGAGMTJLEUOLJC-HXUWFJFHSA-N 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 206010039966 Senile dementia Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- -1 cyano, phenyl Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 229960003444 immunosuppressant agent Drugs 0.000 claims 1
- 239000003018 immunosuppressive agent Substances 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
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- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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Claims (9)
1. Соединение формулы I
где R1 означает С1-С6алкил, необязательно замещенный группами ОН, С1-С2алкокси или 1-6 атомами фтора; С2-С6алкенил или С2-С6алкинил;
R2 означает радикал формулы a, b или с
где R6 означает С1-С12алкил, необязательно замещенный группами: галоген, необязательно замещенный циклоалкил, необязательно замещенный фенил, необязательно замещенный гетероарил или необязательно замещенный гетероциклил, причем С1-С12алкил необязательно прерывается одним или более О или С=О, а фенил, гетероарил, циклоалкил и/или гетероциклический остаток необязательно замещены 1-5 заместителями, выбранными из группы, включающей гидрокси, галоген, С1-С4алкил, С1-С4алкил, замещенный 1-5 атомами фтора, С1-С4алкокси, С1-С4алкокси, замещенный 1-5 атомами фтора, циано, фенил и фенил, замещенный 1-5 заместителями, выбранными из группы, включающей гидрокси, галоген, С1-С4алкил, С1-С4алкокси и циано;
R7 означает Н, необязательно замещенный фенил, необязательно замещенный гетероарил, причем фенил и/или гетероарил независимо замещены 1-5 заместителями, выбранными из группы, включающей гидрокси, галоген, С1-С4алкил, С1-С4алкил, замещенный 1-5 атомами фтора, С1-С4алкокси, С1-С4алкокси, замещенный 1-5 атомами фтора, и циано;
Х означает О, С=O, S или химическую связь;
Z означает N или О;
R3 означает -А-В-СООН, где А и В каждый независимо означает химическую связь, С=O или CDE, где D и Е каждый независисимо означает И, галоген, C1-С3алкил, ОН, при условии, если А и В оба не означают С=O, а каждый R4 и R5 независимо означает Н, С1-С4алкил, необязательно замещенный 1, 2 или 3 атомами галогена, или ацил,
при условии, если R4 означает Н, R5 означает Н, R3 означает СООН, R2 означает радикал формулы a, a R7 означает Н,
i) R1 означает CH2OH, a XR6 означает незамещенный радикал С1-С12алкил, то XR6 не находится в пара-положении к (CH2)2-CR1R3(NR4R5);
ii) или R1 означает СН3, a XR6 означает незамещенный радикал ОС1-С12алкил, то XR6 не находится в мета-положении к (CH2)2-CR1R3(NR4R5), в свободной форме или в форме соли.
3. Соединение по п.1 или 2, которое выбирают из группы, включающей (R)-3-амино-5-(4-гептилоксифенил)-3-метилпентановую кислоту, (R)-4-амино-6-(4-гептилоксифенил)-4-метилгексановую кислоту и (R)-2-амино-4-(4-гептилоксифенил)-2-метилмасляную кислоту.
4. Фармацевтическая композиция, содержащая соединение по любому из пп.1-3 в свободной форме или в форме фармацевтически приемлемой соли в смеси с одним или более фармацевтически приемлемых разбавителей или носителей.
5. Соединение по любому из пп.1-3 в свободной форме или в форме фармацевтически приемлемой соли или композиция по п.4 для применения в качестве лекарственного средства.
6. Применение соединения по любому из пп.1-3 в свободной форме или в форме фармацевтически приемлемой соли или фармацевтической композиции по п.4 для получения лекарственного средства, предназначенного для лечения или профилактики отторжения аллотрансплантата, аутоиммунного заболевания, реакции трансплантат против хозяина, воспалительных заболеваний, миокардита, гепатита, повреждения при ишемии/реперфузии, геморрагического шока, травматического шока, ангиогенеза, болезни Альцгеймера, рака, инфекционных заболеваний или старческой деменции.
7. Фармацевтическая комбинация, включающая соединение по любому из пп.1-3 в свободной форме или в форме фармацевтически приемлемой соли и дополнительный агент, выбранный из группы, включающей иммунодепрессанты, иммуномодуляторы, противовоспалительные и химиотерапевтические агенты.
8. Способ получения соединения по п.1, включающий удаление защитной группы, присутствующей в соединении формулы II
где R1, R2 и R5 имеют значения, указанные в п.1, R3' означает -A-B-COOR8, где А и В имеют значения, указанные в п.1, R8 означает гидролизуемую или отщеплямую гидрированием группу, a R4' означает аминозащитную группу, и при необходимости превращение соединений формулы I, полученных в свободной форме, в требуемую солевую форму, или наоборот.
9. Способ лечения или профилактики отторжения аллотрансплантата, аутоиммунного заболевания, реакции трансплантат против хозяина, воспалительных заболеваний, миокардита, гепатита, повреждений при ишемии/реперфузии, геморрагического шока, травматического шока, ангиогенеза, болезни Альцгеймера, рака, инфекционных заболеваний или старческой деменции, причем указанный способ включает введение указанному субъекту терапевтически эффективного количества соединения по любому из пп.1-3 в свободной форме или в форме фармацевтически приемлемой соли или фармацевтической композиции по п.4.
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GBGB0405289.0A GB0405289D0 (en) | 2004-03-09 | 2004-03-09 | Organic compounds |
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US (1) | US7728020B2 (ru) |
EP (1) | EP1725519A1 (ru) |
JP (1) | JP4441677B2 (ru) |
CN (1) | CN1934069A (ru) |
AU (1) | AU2005219562B2 (ru) |
BR (1) | BRPI0508610A (ru) |
CA (1) | CA2558167A1 (ru) |
GB (1) | GB0405289D0 (ru) |
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WO2004096757A1 (en) * | 2003-04-30 | 2004-11-11 | Novartis Ag | Aminopropanol derivatives as sphingosine-1-phosphate receptor modulators |
SI1772145T1 (sl) | 2004-07-16 | 2011-06-30 | Kyorin Seiyaku Kk | Postopek za učinkovito uporabo zdravila in postopek za preprečevanje stranskih učinkov |
JP2008509931A (ja) | 2004-08-13 | 2008-04-03 | プレーシス ファーマスーティカルズ インコーポレイテッド | スフィンゴシン−1−ホスフェート(s1p)レセプター活性を調節するための方法および組成物 |
US7795472B2 (en) | 2004-10-12 | 2010-09-14 | Kyorin Pharmaceutical Co., Ltd. | Process for producing 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-1,3-propanediol hydrochloride and hydrates thereof, and intermediates in the production thereof |
EP1799217A4 (en) * | 2004-10-12 | 2008-01-23 | Forbes Medi Tech Res Inc | Compositions and methods for treating insulin resistance and cardiomyopathy |
CN101166524B (zh) | 2005-04-28 | 2010-12-22 | 辉瑞有限公司 | 氨基酸衍生物 |
BRPI0617077A2 (pt) * | 2005-10-07 | 2015-01-06 | Kyorin Seiyaku Kk | Agente terapêutico para tratamento de doenças do fígado contendo 2-amina-1, 3-propanediol derivativo como ingrediente ativo, e método para tratamento de doenças do fígado |
TWI389683B (zh) * | 2006-02-06 | 2013-03-21 | Kyorin Seiyaku Kk | A therapeutic agent for an inflammatory bowel disease or an inflammatory bowel disease treatment using a 2-amino-1,3-propanediol derivative as an active ingredient |
KR20090041424A (ko) * | 2006-08-08 | 2009-04-28 | 교린 세이야꾸 가부시키 가이샤 | 아미노알코올 유도체 및 그것들을 유효성분으로 하는 면역 억제제 |
WO2008018427A1 (fr) | 2006-08-08 | 2008-02-14 | Kyorin Pharmaceutical Co., Ltd. | Dérivé d'ester de l'acide aminophosphorique et modulateur du récepteur s1p contenant ledit dérivé en tant que principe actif |
JP2009269819A (ja) * | 2006-08-25 | 2009-11-19 | Asahi Kasei Pharma Kk | アミン化合物 |
US8476305B2 (en) | 2008-02-07 | 2013-07-02 | Kyorin Pharmaceutical Co., Ltd. | Therapeutic agent or prophylactic agent for inflammatory bowel disease comprising amino alcohol derivative as active ingredient |
KR20180023049A (ko) | 2008-07-23 | 2018-03-06 | 아레나 파마슈티칼스, 인크. | 자가면역성 및 염증성의 장애의 치료에 유용한 치환된 1,2,3,4-테트라히드로시클로펜타[b]인돌-3-일)아세트산 유도체 |
CA2733970A1 (en) * | 2008-08-12 | 2010-02-18 | Allergan, Inc. | Sphingosine-1-phosphate (s1p) receptor antagonists and methods for use thereof |
PT2342205T (pt) | 2008-08-27 | 2016-07-28 | Arena Pharm Inc | Derivados de ácido tricíclico substituído como agonistas de recetor s1p1 úteis no tratamento de distúrbios autoimunes e inflamatórios |
WO2011094008A1 (en) | 2010-01-27 | 2011-08-04 | Arena Pharmaceuticals, Inc. | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
ES2558087T3 (es) | 2010-03-03 | 2016-02-01 | Arena Pharmaceuticals, Inc. | Procesos para la preparación de moduladores del receptor S1P1 y formas cristalinas de los mismos |
EP4445956A2 (en) | 2015-01-06 | 2024-10-16 | Arena Pharmaceuticals, Inc. | Compound for use in treating conditions related to the s1p1 receptor |
WO2016209809A1 (en) | 2015-06-22 | 2016-12-29 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(compound1) for use in sipi receptor-associated disorders |
WO2018151873A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
MA47503A (fr) | 2017-02-16 | 2021-04-21 | Arena Pharm Inc | Composés et méthodes pour le traitement de maladies inflammatoires chroniques de l'intestin avec manifestations extra-intestinales |
KR20210074291A (ko) | 2018-09-06 | 2021-06-21 | 아레나 파마슈티칼스, 인크. | 자가면역 및 염증성 장애의 치료에 유용한 화합물 |
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US7326801B2 (en) * | 2001-03-26 | 2008-02-05 | Novartis Ag | 2-amino-propanol derivatives |
CN100351244C (zh) * | 2002-05-27 | 2007-11-28 | 诺瓦提斯公司 | 双芳族链烷醇 |
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EP1725519A1 (en) | 2006-11-29 |
WO2005085179A1 (en) | 2005-09-15 |
JP2007535499A (ja) | 2007-12-06 |
JP4441677B2 (ja) | 2010-03-31 |
CA2558167A1 (en) | 2005-09-15 |
BRPI0508610A (pt) | 2007-07-31 |
AU2005219562B2 (en) | 2008-10-16 |
US20070135501A1 (en) | 2007-06-14 |
CN1934069A (zh) | 2007-03-21 |
US7728020B2 (en) | 2010-06-01 |
GB0405289D0 (en) | 2004-04-21 |
RU2379281C2 (ru) | 2010-01-20 |
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