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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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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| UY33178A (es) * | 2010-01-13 | 2011-08-31 | Sanofi Aventis | Derivados de ácido carboxílico heteroxíclicos que comprenden un anillo de oxazolopirimidina 2, 5, 7-sustituido |
| TWI485153B (zh) * | 2010-01-13 | 2015-05-21 | Sanofi Aventis | ２，５，７－經取代唑并嘧啶衍生物 |
| 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 |
| JP5841068B2 (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環を有する複素環式カルボン酸誘導体 |
| MX2012007837A (es) * | 2010-01-14 | 2012-07-30 | Sanofi Sa | Derivados de oxazolopirimidina 2, 5 - sustituidos. |
| TW201206429A (en) * | 2010-07-08 | 2012-02-16 | Merck Serono Sa | Substituted oxadiazole derivatives |
| TW201217387A (en) | 2010-09-15 | 2012-05-01 | Hoffmann La Roche | Azabenzothiazole compounds, compositions and methods of use |
| JP5999387B2 (ja) * | 2011-03-25 | 2016-09-28 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｒｔｈ２拮抗薬としてのピラゾール化合物 |
| US9321787B2 (en) * | 2011-07-07 | 2016-04-26 | Sanofi | Carboxylic acid derivatives having an oxazolo[5,4-d]pyrimidine ring |
| 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 |
| WO2013158422A1 (en) | 2012-04-17 | 2013-10-24 | E. I. Du Pont De Nemours And Company | Heterocyclic compounds for controlling invertebrate pests |
| JP6021915B2 (ja) * | 2012-07-20 | 2016-11-09 | 三菱電機株式会社 | 保持フレームおよび太陽電池モジュール |
| 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 |
| AU2014308991B2 (en) | 2013-08-21 | 2019-02-14 | Janssen Biopharma, Inc. | Antiviral compounds |
| WO2016182850A1 (en) | 2015-05-08 | 2016-11-17 | 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 |
| JP7252908B2 (ja) * | 2017-06-14 | 2023-04-05 | トレベナ・インコーポレイテッド | Ｓ１ｐ１活性を調節するための化合物およびその使用法 |
| MX2022005766A (es) * | 2019-11-19 | 2022-08-08 | Trevena Inc | Compuestos y métodos para la preparación de compuestos moduladores de esfingosina 1-fosfato tipo 1 (s1p1). |
| 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 |
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| JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
| ATE420869T1 (de) | 2000-10-05 | 2009-01-15 | Takeda Pharmaceutical | Promotoren zur proliferation und differenzierung von stammzellen und/oder vorstufen von neuronenzellen |
| WO2002072549A1 (en) | 2001-03-12 | 2002-09-19 | Millennium Pharmaceuticals, Inc. | Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor |
| EP1460067A4 (en) | 2001-11-26 | 2005-12-07 | Takeda Pharmaceutical | BICYCLIC DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE |
| JP4430941B2 (ja) | 2002-01-18 | 2010-03-10 | メルク エンド カムパニー インコーポレーテッド | Ｅｄｇ受容体作動薬 |
| EP1620413A2 (en) | 2003-04-30 | 2006-02-01 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| MXPA05011597A (es) * | 2003-04-30 | 2005-12-15 | Novartis Ag | Derivados de aminopropanol como moduladores del receptor 1-fosfato de esfingosina. |
| CL2004001120A1 (es) * | 2003-05-19 | 2005-04-15 | Irm Llc | Compuestos derivados de amina sustituidas con heterociclos, inmunosupresores; composicion farmaceutica; y uso para tratar enfermedades mediadas por interacciones de linfocito, tales como enfermedades autoinmunes, inflamatorias, infecciosas, cancer. |
| EP2402323A3 (en) | 2004-10-13 | 2012-05-30 | PTC Therapeutics, Inc. | Pyrazole or triazole compounds and their use for the manufacture of a medicament for treating somatic mutation-related diseases |
| EP1965807A4 (en) | 2005-11-23 | 2010-10-27 | Epix Delaware Inc | S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE |
| US7919519B2 (en) * | 2005-11-23 | 2011-04-05 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| US20090182003A1 (en) | 2006-01-13 | 2009-07-16 | President And Fellows Of Harvard College | Methods and Compositions for Treatment Cell Proliferative Disorders |
| JP2009526761A (ja) | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| EP1987396B1 (en) | 2006-02-08 | 2010-05-26 | Kodak Graphic Communications GmbH | Uv-sensitive lithographic printing plate precursor with benzoxazole derivative and analogues thereof as sensitizer |
| AU2007227274A1 (en) | 2006-03-21 | 2007-09-27 | 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 |
| JP2010510245A (ja) | 2006-11-21 | 2010-04-02 | スミスクライン ビーチャム コーポレーション | 抗ウイルス化合物 |
| WO2008073865A2 (en) | 2006-12-11 | 2008-06-19 | Novartis Ag | Method of preventing or treating myocardial ischemia |
| JP5191497B2 (ja) * | 2007-03-21 | 2013-05-08 | エピックス ファーマシューティカルズ，インコーポレイテッド | Ｓ１ｐ受容体調節化合物およびその使用 |
| 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 |
| AU2008302746B2 (en) | 2007-09-20 | 2014-07-03 | Amgen Inc. | 1-(4-(benzylbenzamid0) -benzyl) azetidine-3-carboxylic acid derivatives and related compounds as SlP receptor modulators for the treatment of immune disorders |
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2009
- 2009-06-11 TW TW098119601A patent/TW201000099A/zh unknown
- 2009-06-18 ES ES09767088T patent/ES2433579T3/es active Active
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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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| CA2728046A1 (en) | 2009-12-23 |
| EP2306994A4 (en) | 2011-08-03 |
| US7842685B2 (en) | 2010-11-30 |
| ES2433579T3 (es) | 2013-12-11 |
| AR072185A1 (es) | 2010-08-11 |
| JP5571073B2 (ja) | 2014-08-13 |
| EP2306994A1 (en) | 2011-04-13 |
| WO2009154780A1 (en) | 2009-12-23 |
| JP2011524906A (ja) | 2011-09-08 |
| MX2010013555A (es) | 2011-01-14 |
| EP2306994B1 (en) | 2013-08-14 |
| US20120129828A1 (en) | 2012-05-24 |
| US20100029611A1 (en) | 2010-02-04 |
| AU2009260726B2 (en) | 2014-03-27 |
| AU2009260726A1 (en) | 2009-12-23 |
| WO2009154775A1 (en) | 2009-12-23 |
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