CA2655675A1 - Substituted n-phenylmethyl -5-oxo-proline-2-amides as p2x7-receptor antagonists and their methods of use - Google Patents
Substituted n-phenylmethyl -5-oxo-proline-2-amides as p2x7-receptor antagonists and their methods of use Download PDFInfo
- Publication number
- CA2655675A1 CA2655675A1 CA002655675A CA2655675A CA2655675A1 CA 2655675 A1 CA2655675 A1 CA 2655675A1 CA 002655675 A CA002655675 A CA 002655675A CA 2655675 A CA2655675 A CA 2655675A CA 2655675 A1 CA2655675 A1 CA 2655675A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- mmol
- mixture
- phenyl
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 116
- 101710189965 P2X purinoceptor 7 Proteins 0.000 title abstract description 29
- 102100037602 P2X purinoceptor 7 Human genes 0.000 title abstract description 29
- 239000002464 receptor antagonist Substances 0.000 title description 7
- 229940044551 receptor antagonist Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 117
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 208000002193 Pain Diseases 0.000 claims abstract description 26
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- 230000004770 neurodegeneration Effects 0.000 claims abstract description 11
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- 230000004054 inflammatory process Effects 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- -1 pyridinylmethyl- Chemical group 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 150000002431 hydrogen Chemical class 0.000 claims description 25
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000005002 aryl methyl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
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- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 342
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 60
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- 125000000217 alkyl group Chemical group 0.000 description 27
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- 238000003786 synthesis reaction Methods 0.000 description 21
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- SHLYZEAOVWVTSW-BYPYZUCNSA-N (2s)-1-methyl-5-oxopyrrolidine-2-carboxylic acid Chemical compound CN1[C@H](C(O)=O)CCC1=O SHLYZEAOVWVTSW-BYPYZUCNSA-N 0.000 description 19
- 239000000463 material Substances 0.000 description 19
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- 238000001704 evaporation Methods 0.000 description 17
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- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PL2049478T3 (pl) | 2006-07-06 | 2012-09-28 | Glaxo Group Ltd | Podstawione N-fenylometylo 5-okso-prolino-2-amidy jako antagoniści receptora P2X7 oraz sposoby ich zastosowania |
| DE102006047619B4 (de) * | 2006-10-09 | 2008-11-13 | Clariant International Limited | Verfahren zur Herstellung basischer Fettsäureamide |
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| DE102008017216B4 (de) * | 2008-04-04 | 2013-08-14 | Clariant International Ltd. | Kontinuierliches Verfahren zur Herstellung von Fettsäureamiden |
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| DE102008017215B4 (de) * | 2008-04-04 | 2012-08-09 | Clariant International Ltd. | Kontinuierliches Verfahren zur Herstellung von Amiden ethylenisch ungesättigter Carbonsäuren |
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| DE102008017213B4 (de) * | 2008-04-04 | 2012-08-09 | Clariant International Limited | Kontinuierliches Verfahren zur Herstellung von Amiden aliphatischer Hydroxycarbonsäuren |
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| DE102009042522A1 (de) | 2009-09-22 | 2011-04-07 | Clariant International Ltd. | Kontinuierliches Umesterungsverfahren |
| DE102009042523B4 (de) | 2009-09-22 | 2012-02-16 | Clariant International Ltd. | Vorrichtung und Verfahren zur kontinuierlichen Durchführung heterogen katalysierter chemischer Reaktionen bei hohen Temperaturen |
| ES2710522T3 (es) | 2009-12-08 | 2019-04-25 | Univ Vanderbilt | Procedimientos y composiciones para la extracción de venas y autotransplante |
| CA2792258A1 (en) | 2010-03-05 | 2011-09-09 | President And Fellows Of Harvard College | Induced dendritic cell compositions and uses thereof |
| CN102858741A (zh) | 2010-05-14 | 2013-01-02 | 阿费克蒂斯制药股份公司 | 制备p2x7r拮抗剂的新方法 |
| DE102010056565A1 (de) | 2010-12-30 | 2012-07-05 | Clariant International Ltd. | Verfahren zur Modifizierung Hydroxylgruppen tragender Polymere |
| DE102010056564A1 (de) | 2010-12-30 | 2012-07-05 | Clariant International Limited | Hydroxylgruppen und Estergruppen tragende Polymere und Verfahren zu ihrer Herstellung |
| WO2012093101A1 (en) * | 2011-01-04 | 2012-07-12 | Novartis Ag | Indole compounds or analogues thereof useful for the treatment of age-related macular degeneration (amd) |
| WO2012110190A1 (en) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| US20140187533A1 (en) * | 2011-03-03 | 2014-07-03 | Zalicus Pharmaceuticals Ltd. | Benzimidazole inhibitors of the sodium channel |
| CA2831932A1 (en) | 2011-04-01 | 2012-10-04 | Genentech, Inc. | Combinations of akt and mek inhibitor compounds, and methods of use |
| RS56759B2 (sr) | 2011-04-01 | 2024-10-31 | Genentech Inc | Kombinacija akt inhibitor jedinjenja i abiraterona za upotrebu pri terapeutskim tretiranjima |
| WO2012163792A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163456A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| ES2574840T3 (es) | 2011-07-22 | 2016-06-22 | Actelion Pharmaceuticals Ltd. | Derivados de amidas heterocíclicas como antagonistas de receptores p2x7 |
| KR102033190B1 (ko) | 2012-01-20 | 2019-10-16 | 이도르시아 파마슈티컬스 리미티드 | Ｐ２ｘ７ 수용체 길항제로서의 헤테로시클릭 아미드 유도체 |
| US9075975B2 (en) * | 2012-02-21 | 2015-07-07 | Andrew Bud | Online pseudonym verification and identity validation |
| EA029644B1 (ru) | 2012-12-12 | 2018-04-30 | Идорсиа Фармасьютиклз Лтд | Индолкарбоксамидные производные в качестве антагонистов p2xрецепторов |
| CA2891499C (en) | 2012-12-18 | 2021-07-06 | Actelion Pharmaceuticals Ltd | Indole carboxamide derivatives as p2x7 receptor antagonists |
| CA2896790C (en) | 2013-01-22 | 2022-05-10 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
| KR102220847B1 (ko) | 2013-01-22 | 2021-02-26 | 이도르시아 파마슈티컬스 리미티드 | Ｐ2ｘ7 수용체 길항제로서의 헤테로시클릭 아미드 유도체 |
| TWI636047B (zh) | 2013-08-14 | 2018-09-21 | 英商卡爾維斯塔製藥有限公司 | 雜環衍生物 |
| FR3026102A1 (fr) * | 2014-09-19 | 2016-03-25 | Univ Nice Sophia Antipolis | Conjugues d'acide amine-pyridine/pyridinium et leurs utilisations en tant qu'agents biocides |
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| JP6884801B2 (ja) | 2016-05-31 | 2021-06-09 | カルビスタ・ファーマシューティカルズ・リミテッド | 血漿カリクレインインヒビターとしてのピラゾール誘導体 |
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| DK3609868T3 (da) * | 2017-03-13 | 2023-11-27 | Raqualia Pharma Inc | Tetrahydroquinolinderivater som P2X7-receptorantagonister |
| WO2019006074A1 (en) * | 2017-06-28 | 2019-01-03 | Indiana University Research And Technology Corporation | PHARMACEUTICAL AGENT THAT RELATES TO THE P2X7 RECEIVER |
| GB201719881D0 (en) | 2017-11-29 | 2018-01-10 | Kalvista Pharmaceuticals Ltd | Solid forms of plasma kallikrein inhibitor and salts thereof |
| MX2020005168A (es) | 2017-11-29 | 2020-08-20 | Kalvista Pharmaceuticals Ltd | Formas de dosificacion que contienen un inhibidor calicreina de plasma. |
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| JP2023521623A (ja) | 2020-03-31 | 2023-05-25 | ノモレイティス・ベスローテン・フェンノートシャップ | 過炎症性症候群の処置 |
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| JPH0699307B2 (ja) * | 1987-08-20 | 1994-12-07 | キッセイ薬品工業株式会社 | 抗痴呆剤 |
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| JP2010522711A (ja) * | 2007-03-28 | 2010-07-08 | グラクソ グループ リミテッド | Ｐ２ｘ７調節因子としてのピペリジノンカルボキサミド誘導体 |
| JP2010522710A (ja) * | 2007-03-29 | 2010-07-08 | グラクソ グループ リミテッド | Ｐ２ｘ７調節因子としてのオキサゾリジンおよびモルホリンカルボキサミド誘導体 |
| WO2008119825A2 (en) * | 2007-04-03 | 2008-10-09 | Glaxo Group Limited | Imidazolidine carboxamide derivatives as p2x7 modulators |
| CN101772498A (zh) * | 2007-04-10 | 2010-07-07 | H.隆德贝克有限公司 | 作为p2x7拮抗剂的杂芳基酰胺类似物 |
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2010
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Effective date: 20150924 |