MX2010013555A - Agonistas del receptor de esfingosin 1-fosfato 1 y uso de los mismos. - Google Patents
Agonistas del receptor de esfingosin 1-fosfato 1 y uso de los mismos.Info
- Publication number
- MX2010013555A MX2010013555A MX2010013555A MX2010013555A MX2010013555A MX 2010013555 A MX2010013555 A MX 2010013555A MX 2010013555 A MX2010013555 A MX 2010013555A MX 2010013555 A MX2010013555 A MX 2010013555A MX 2010013555 A MX2010013555 A MX 2010013555A
- Authority
- MX
- Mexico
- Prior art keywords
- fluoro
- thiazolo
- phenyl
- pyridin
- cyclopropyl
- Prior art date
Links
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title abstract description 10
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title abstract description 10
- 239000000018 receptor agonist Substances 0.000 title abstract 2
- 229940044601 receptor agonist Drugs 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 120
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 8
- -1 and R 1 is or Chemical group 0.000 claims description 543
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 204
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 148
- 239000002253 acid Substances 0.000 claims description 103
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 101
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 claims description 66
- 229920006395 saturated elastomer Polymers 0.000 claims description 59
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 58
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 46
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 42
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 39
- 125000001188 haloalkyl group Chemical group 0.000 claims description 37
- WFIHKLWVLPBMIQ-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridine Chemical compound C1=CN=C2SC=NC2=C1 WFIHKLWVLPBMIQ-UHFFFAOYSA-N 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 29
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 19
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 18
- 235000019260 propionic acid Nutrition 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 15
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 229910019142 PO4 Inorganic materials 0.000 claims description 10
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
- 239000010452 phosphate Substances 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 claims description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 3
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 235000009582 asparagine Nutrition 0.000 claims description 2
- 229960001230 asparagine Drugs 0.000 claims description 2
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 1
- 229910052793 cadmium Inorganic materials 0.000 claims 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical group [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 claims 1
- 229940125898 compound 5 Drugs 0.000 claims 1
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims 1
- 125000004404 heteroalkyl group Chemical group 0.000 claims 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
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Classifications
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7447608P | 2008-06-20 | 2008-06-20 | |
| PCT/US2009/003666 WO2009154775A1 (en) | 2008-06-20 | 2009-06-18 | S1p1 receptor agonists and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2010013555A true MX2010013555A (es) | 2011-01-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2010013555A MX2010013555A (es) | 2008-06-20 | 2009-06-18 | Agonistas del receptor de esfingosin 1-fosfato 1 y uso de los mismos. |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US7842685B2 (enExample) |
| EP (1) | EP2306994B1 (enExample) |
| JP (1) | JP5571073B2 (enExample) |
| AR (1) | AR072185A1 (enExample) |
| AU (1) | AU2009260726B2 (enExample) |
| CA (1) | CA2728046A1 (enExample) |
| ES (1) | ES2433579T3 (enExample) |
| MX (1) | MX2010013555A (enExample) |
| TW (1) | TW201000099A (enExample) |
| WO (2) | WO2009154780A1 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR079980A1 (es) * | 2010-01-13 | 2012-03-07 | Sanofi Aventis | Derivados de oxazolopirimidina sustituida en 2,5,7 |
| 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. |
| 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 |
| MX2012007834A (es) * | 2010-01-14 | 2012-07-30 | Sanofi Sa | Derivados de acido carboxilico que comprenden un anillo de oxazolopirimidina 2,5-sustituido. |
| 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 |
| PT2523960E (pt) * | 2010-01-14 | 2013-12-09 | Sanofi Sa | Derivados heterocíclicos de ácidos carboxílicos com um anel oxazolopirimidina substituído em 2,5 |
| TW201206429A (en) * | 2010-07-08 | 2012-02-16 | Merck Serono Sa | Substituted oxadiazole derivatives |
| RU2013114352A (ru) | 2010-09-15 | 2014-10-20 | Ф. Хоффманн-Ля Рош Аг | Азабензотиазолы, композиции и способы применения |
| US9206164B2 (en) * | 2011-03-25 | 2015-12-08 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as CRTH2 antagonists |
| US8907093B2 (en) * | 2011-07-07 | 2014-12-09 | Sanofi | Carboxylic acid derivatives having an oxazolo[4,5-c]pyridine ring |
| US8735402B2 (en) | 2011-07-07 | 2014-05-27 | Sanofi | Cycloalkyloxycarboxylic acid derivatives |
| US8580816B2 (en) * | 2011-07-07 | 2013-11-12 | Sanofi | Carboxylic acid derivatives having an oxazolo[5,4-b]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 |
| WO2014013611A1 (ja) * | 2012-07-20 | 2014-01-23 | 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 |
| CA2901527A1 (en) | 2013-02-20 | 2014-08-28 | Bayer Pharma Aktiengesellschaft | Substituted-imidazo[1,2-b]pyridazines as mknk1 inhibitors |
| HK1225716A1 (zh) | 2013-08-21 | 2017-09-15 | Alios Biopharma, Inc. | 抗病毒化合物 |
| 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 |
| IL271149B2 (en) | 2017-06-14 | 2024-05-01 | Trevena Inc | Compounds for modulating s1p1 activity and methods of using the same |
| 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 |
| WO2021101854A1 (en) * | 2019-11-19 | 2021-05-27 | 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 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000038350A (ja) | 1998-05-18 | 2000-02-08 | Yoshitomi Pharmaceut Ind Ltd | 糖尿病治療薬 |
| ES2317935T3 (es) | 2000-10-05 | 2009-05-01 | Takeda Pharmaceutical Company Limited | Promotores de la proliferacion y diferenciacion de celulas pluripotenciales y/o celulas precursoras neuronales. |
| EP1377549A1 (en) | 2001-03-12 | 2004-01-07 | 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 |
| ATE441654T1 (de) | 2002-01-18 | 2009-09-15 | Merck & Co Inc | Edg-rezeptoragonisten |
| WO2004098494A2 (en) | 2003-04-30 | 2004-11-18 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| WO2004096757A1 (en) * | 2003-04-30 | 2004-11-11 | Novartis Ag | Aminopropanol derivatives as sphingosine-1-phosphate receptor modulators |
| WO2005000833A1 (en) * | 2003-05-19 | 2005-01-06 | Irm, Llc | Immunosuppressant compounds and compositions |
| WO2006044456A1 (en) | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Compounds for nonsense suppression, and methods for their use |
| 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 |
| WO2007084857A2 (en) | 2006-01-13 | 2007-07-26 | President And Fellows Of Harvard College | Methods and compositions for treating cell proliferative disorders |
| EP1989211A2 (en) | 2006-01-30 | 2008-11-12 | Array Biopharma, Inc. | Heterobicyclic thiophene compounds for the treatment of cancer |
| JP4897834B2 (ja) | 2006-02-08 | 2012-03-14 | コダック グラフィック コミュニケーションズ ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンゾキサゾール誘導体およびその類似体を増感剤として含む紫外線感受性平版印刷版前駆体 |
| TW200806633A (en) * | 2006-03-21 | 2008-02-01 | Epix Pharm Inc | S1P receptor modulating compounds and use thereof |
| EP2001472A2 (en) | 2006-03-23 | 2008-12-17 | Merck and Co., Inc. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| TW200831084A (en) | 2006-11-21 | 2008-08-01 | Genelabs Tech Inc | Anti-viral compounds |
| JP2010512410A (ja) | 2006-12-11 | 2010-04-22 | ノバルティス アーゲー | 心筋虚血を予防または処置するための方法 |
| 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 |
| MX2010002885A (es) * | 2007-09-20 | 2010-04-01 | Amgen Inc | Derivados de acido 1-(4-(bencilbenzamido)-bencil)-azetidin-3-carbo xilico y compuestos relacionados como moduladores de receptores de s1p para el tratamiento de trastornos inmunitarios. |
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| AU2009260726A1 (en) | 2009-12-23 |
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| EP2306994A1 (en) | 2011-04-13 |
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| US7842685B2 (en) | 2010-11-30 |
| AU2009260726B2 (en) | 2014-03-27 |
| TW201000099A (en) | 2010-01-01 |
| CA2728046A1 (en) | 2009-12-23 |
| WO2009154775A1 (en) | 2009-12-23 |
| US20100029611A1 (en) | 2010-02-04 |
| JP2011524906A (ja) | 2011-09-08 |
| JP5571073B2 (ja) | 2014-08-13 |
| EP2306994A4 (en) | 2011-08-03 |
| WO2009154780A1 (en) | 2009-12-23 |
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