TW201000099A - S1P1 receptor agonists and use thereof - Google Patents
S1P1 receptor agonists and use thereof Download PDFInfo
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- TW201000099A TW201000099A TW098119601A TW98119601A TW201000099A TW 201000099 A TW201000099 A TW 201000099A TW 098119601 A TW098119601 A TW 098119601A TW 98119601 A TW98119601 A TW 98119601A TW 201000099 A TW201000099 A TW 201000099A
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- Taiwan
- Prior art keywords
- phenyl
- fluoro
- phenylcyclopropyl
- thiazolo
- group
- Prior art date
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- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title claims abstract description 18
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title claims abstract description 18
- 229940044601 receptor agonist Drugs 0.000 title abstract description 7
- 239000000018 receptor agonist Substances 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 189
- -1 heterocyclic amine Chemical class 0.000 claims description 445
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 351
- 125000000217 alkyl group Chemical group 0.000 claims description 192
- 201000006417 multiple sclerosis Diseases 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 128
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 123
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 120
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 114
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 88
- 125000001188 haloalkyl group Chemical group 0.000 claims description 76
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 69
- 229920006395 saturated elastomer Polymers 0.000 claims description 68
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 61
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 60
- 229910052731 fluorine Inorganic materials 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 54
- 239000002253 acid Substances 0.000 claims description 51
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 44
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 40
- 125000003277 amino group Chemical group 0.000 claims description 33
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 31
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 29
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 150000001412 amines Chemical class 0.000 claims description 27
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 26
- 239000007789 gas Substances 0.000 claims description 26
- 239000000460 chlorine Substances 0.000 claims description 25
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 239000011734 sodium Substances 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- 235000019260 propionic acid Nutrition 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 18
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 claims description 18
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 18
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- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 16
- 229910052708 sodium Inorganic materials 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 150000002923 oximes Chemical class 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 13
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 12
- WFIHKLWVLPBMIQ-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridine Chemical compound C1=CN=C2SC=NC2=C1 WFIHKLWVLPBMIQ-UHFFFAOYSA-N 0.000 claims description 12
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 12
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 210000003802 sputum Anatomy 0.000 claims description 6
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- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 5
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Classifications
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Landscapes
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Cited By (3)
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| CN102791717A (zh) * | 2010-01-14 | 2012-11-21 | 赛诺菲 | 具有2,5-取代的噁唑并嘧啶环的羧酸衍生物 |
| CN103797015A (zh) * | 2011-07-07 | 2014-05-14 | 赛诺菲 | 具有噁唑并[4,5-c]吡啶环的羧酸衍生物 |
| CN110256466A (zh) * | 2019-07-31 | 2019-09-20 | 昆山迪安医学检验实验室有限公司 | 一种噻唑[5,4-b]-吡啶基生物活性化合物的制备方法及其抗肿瘤活性的检测 |
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| AR079980A1 (es) * | 2010-01-13 | 2012-03-07 | Sanofi Aventis | Derivados de oxazolopirimidina sustituida en 2,5,7 |
| TWI478929B (zh) | 2010-01-13 | 2015-04-01 | Sanofi Aventis | 含２，５，７－經取代唑并嘧啶環之羧酸衍生物 |
| AR079982A1 (es) * | 2010-01-13 | 2012-03-07 | Sanofi Aventis | Derivados de acido carboxilico heterociclicos que comprenden un anillo de oxazolopirimidina 2,5,7- sustituido., composiciones farmaceuticas y procesos para prepararlos. |
| TWI482623B (zh) * | 2010-01-14 | 2015-05-01 | Sanofi Aventis | 包含２，５－經取代的唑并嘧啶環之雜環性羧酸衍生物類 |
| JP5841069B2 (ja) | 2010-01-14 | 2016-01-06 | サノフイ | ２，５−置換されたオキサゾロピリミジン誘導体 |
| TW201206429A (en) * | 2010-07-08 | 2012-02-16 | Merck Serono Sa | Substituted oxadiazole derivatives |
| JP5822934B2 (ja) | 2010-09-15 | 2015-11-25 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | アザベンゾチアゾール化合物、組成物及び使用方法 |
| US9206164B2 (en) * | 2011-03-25 | 2015-12-08 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as CRTH2 antagonists |
| US8580816B2 (en) * | 2011-07-07 | 2013-11-12 | Sanofi | Carboxylic acid derivatives having an oxazolo[5,4-b]pyridine ring |
| US8907093B2 (en) | 2011-07-07 | 2014-12-09 | Sanofi | Carboxylic acid derivatives having an oxazolo[4,5-c]pyridine ring |
| US9321787B2 (en) | 2011-07-07 | 2016-04-26 | Sanofi | Carboxylic acid derivatives having an oxazolo[5,4-d]pyrimidine ring |
| WO2013158422A1 (en) | 2012-04-17 | 2013-10-24 | E. I. Du Pont De Nemours And Company | Heterocyclic compounds for controlling invertebrate pests |
| CN104380596B (zh) * | 2012-07-20 | 2018-01-02 | 三菱电机株式会社 | 保持框架和太阳能电池模块 |
| HK1212699A1 (zh) | 2013-02-20 | 2016-06-17 | 拜耳医药股份公司 | 作为mknk1抑制剂的取代的咪唑并[1，2-b]哒嗪类化合物 |
| BR112016003348B1 (pt) | 2013-08-21 | 2023-03-07 | Alios Biopharma, Inc | Compostos antivirais ou sais farmaceuticamente aceitáveis dos mesmos, composição farmacêutica e seus usos |
| US10597401B2 (en) | 2015-05-08 | 2020-03-24 | Albany Molecular Research, Inc. | Methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof |
| IL252151A0 (en) | 2017-05-07 | 2017-07-31 | Fainzilber Michael | Treatment of stress disorders |
| CN110831593A (zh) * | 2017-06-14 | 2020-02-21 | 特维娜有限公司 | 用于调节s1p1活性的化合物及其使用方法 |
| US11884655B2 (en) | 2019-11-19 | 2024-01-30 | Trevena, Inc. | Compounds and methods of preparing compounds S1P1 modulators |
| CN115611793A (zh) * | 2021-07-14 | 2023-01-17 | 山东新华制药股份有限公司 | 硫代酰胺类化合物的合成方法 |
| CN116410213A (zh) * | 2023-02-21 | 2023-07-11 | 武汉大学 | 一种合成3-碳基-1-硼基环类化合物的方法 |
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| JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
| CA2424870A1 (en) | 2000-10-05 | 2003-04-04 | Takeda Chemical Industries, Ltd. | Agents for promoting the proliferation or differentiation of stem cells or neural progenitor cells |
| US6951848B2 (en) | 2001-03-12 | 2005-10-04 | Millennium Pharmaceuticals, Inc., | Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor |
| US7622479B2 (en) | 2001-11-26 | 2009-11-24 | Takeda Pharmaceutical Company Limited | Bicyclic derivative, its production and use |
| CA2472715A1 (en) | 2002-01-18 | 2003-07-31 | Merck & Co., Inc. | Edg receptor agonists |
| ES2392167T3 (es) * | 2003-04-30 | 2012-12-05 | Novartis Ag | Derivados aminopropanol como moduladores del receptor esfingosina-1-fosfato |
| EP1620413A2 (en) | 2003-04-30 | 2006-02-01 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| US7417065B2 (en) * | 2003-05-19 | 2008-08-26 | Irm Llc | Immunosuppressant compounds and compositions |
| CA2583976A1 (en) | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Use of defined compounds for the manufacture of a medicament for preventing/treating diseases resulting from somatic mutations |
| US7919519B2 (en) * | 2005-11-23 | 2011-04-05 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| US7855193B2 (en) * | 2005-11-23 | 2010-12-21 | Epix Pharmaceuticals, Inc. | S1P receptor modulating compounds and use thereof |
| WO2007084857A2 (en) | 2006-01-13 | 2007-07-26 | President And Fellows Of Harvard College | Methods and compositions for treating cell proliferative disorders |
| US8003662B2 (en) | 2006-01-30 | 2011-08-23 | Array Biopharma, Inc. | Heterobicyclic thiophene compounds and methods of use |
| US8632937B2 (en) | 2006-02-08 | 2014-01-21 | Eastman Kodak Company | UV-sensitive lithographic printing plate precursor with benzoxazole derivative and analogues thereof as sensitizer |
| EP2010524A2 (en) * | 2006-03-21 | 2009-01-07 | Epix Delaware, Inc. | S1p receptor modulating compounds |
| US7989472B2 (en) * | 2006-03-23 | 2011-08-02 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| US20100055071A1 (en) | 2006-11-21 | 2010-03-04 | Martin Robert Leivers | Anti-Viral Compounds |
| WO2008073865A2 (en) | 2006-12-11 | 2008-06-19 | Novartis Ag | Method of preventing or treating myocardial ischemia |
| CA2679980A1 (en) * | 2007-03-21 | 2007-09-27 | Epix Pharmaceuticals, Inc. | S1p receptor modulating compounds and use thereof |
| JP2008308448A (ja) | 2007-06-15 | 2008-12-25 | Sankyo Agro Kk | （３−硫黄原子置換フェニル）へテロアリール誘導体 |
| CA2699417A1 (en) * | 2007-09-20 | 2009-03-26 | Amgen Inc. | S1p receptor modulating compounds and use thereof |
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2009
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- 2009-06-18 EP EP09767088.9A patent/EP2306994B1/en not_active Not-in-force
- 2009-06-18 WO PCT/US2009/003673 patent/WO2009154780A1/en not_active Ceased
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- 2009-06-18 US US12/995,387 patent/US20120129828A1/en not_active Abandoned
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102791717A (zh) * | 2010-01-14 | 2012-11-21 | 赛诺菲 | 具有2,5-取代的噁唑并嘧啶环的羧酸衍生物 |
| CN103797015A (zh) * | 2011-07-07 | 2014-05-14 | 赛诺菲 | 具有噁唑并[4,5-c]吡啶环的羧酸衍生物 |
| CN110256466A (zh) * | 2019-07-31 | 2019-09-20 | 昆山迪安医学检验实验室有限公司 | 一种噻唑[5,4-b]-吡啶基生物活性化合物的制备方法及其抗肿瘤活性的检测 |
Also Published As
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| ES2433579T3 (es) | 2013-12-11 |
| US20100029611A1 (en) | 2010-02-04 |
| MX2010013555A (es) | 2011-01-14 |
| EP2306994A1 (en) | 2011-04-13 |
| AU2009260726A1 (en) | 2009-12-23 |
| WO2009154780A1 (en) | 2009-12-23 |
| AU2009260726B2 (en) | 2014-03-27 |
| JP2011524906A (ja) | 2011-09-08 |
| CA2728046A1 (en) | 2009-12-23 |
| US7842685B2 (en) | 2010-11-30 |
| WO2009154775A1 (en) | 2009-12-23 |
| EP2306994B1 (en) | 2013-08-14 |
| JP5571073B2 (ja) | 2014-08-13 |
| US20120129828A1 (en) | 2012-05-24 |
| EP2306994A4 (en) | 2011-08-03 |
| AR072185A1 (es) | 2010-08-11 |
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