NO324426B1 - 2-aminokarbonyl-9H-purinderivater, samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk sammensetning - Google Patents
2-aminokarbonyl-9H-purinderivater, samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk sammensetning Download PDFInfo
- Publication number
- NO324426B1 NO324426B1 NO20025821A NO20025821A NO324426B1 NO 324426 B1 NO324426 B1 NO 324426B1 NO 20025821 A NO20025821 A NO 20025821A NO 20025821 A NO20025821 A NO 20025821A NO 324426 B1 NO324426 B1 NO 324426B1
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- Norway
- Prior art keywords
- formula
- compound according
- alkyl
- compound
- optionally substituted
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- 238000002360 preparation method Methods 0.000 title claims abstract description 204
- 238000000034 method Methods 0.000 title claims abstract description 66
- 230000008569 process Effects 0.000 title claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- BMHHQPYFORGXQA-UHFFFAOYSA-N 7h-purine-2-carboxamide Chemical class NC(=O)C1=NC=C2N=CNC2=N1 BMHHQPYFORGXQA-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 359
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- 238000006243 chemical reaction Methods 0.000 claims description 61
- 125000006239 protecting group Chemical group 0.000 claims description 60
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 48
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 43
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 31
- 150000001412 amines Chemical class 0.000 claims description 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 30
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 28
- 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
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- 239000003054 catalyst Substances 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 21
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- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
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- 125000002947 alkylene group Chemical group 0.000 claims description 16
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- 150000002367 halogens Chemical group 0.000 claims description 13
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000004263 tetrahydroisoquinolin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])C2=C([H])C([H])=C([H])C([H])=C2C1([H])* 0.000 claims description 9
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- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 8
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- 230000000694 effects Effects 0.000 claims description 7
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
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- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
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- 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 5
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
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- WXTOFTCCIXLSKC-UHFFFAOYSA-N 1-(2-aminoethyl)-3-(1-pyridin-2-ylpiperidin-4-yl)urea;dihydrochloride Chemical compound Cl.Cl.C1CC(NC(=O)NCCN)CCN1C1=CC=CC=N1 WXTOFTCCIXLSKC-UHFFFAOYSA-N 0.000 claims description 3
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- UXVIJLXEICIWMK-CRDHKZEPSA-N ethyl 9-[(2r,3r,4r,5r)-3,4-diacetyloxy-5-(acetyloxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purine-2-carboxylate Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](OC(C)=O)[C@@H](COC(C)=O)O3)OC(C)=O)C2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 UXVIJLXEICIWMK-CRDHKZEPSA-N 0.000 claims description 2
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Classifications
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Landscapes
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
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- Pulmonology (AREA)
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Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0014048A GB0014048D0 (en) | 2000-06-06 | 2000-06-06 | Purine derivatives |
GB0018246A GB0018246D0 (en) | 2000-06-06 | 2000-07-25 | Purine derivatives |
GB0024920A GB0024920D0 (en) | 2000-06-06 | 2000-10-11 | Purine derivatives |
PCT/IB2001/000973 WO2001094368A1 (en) | 2000-06-06 | 2001-06-05 | 2-aminocarbonyl-9h-purine derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20025821D0 NO20025821D0 (no) | 2002-12-04 |
NO20025821L NO20025821L (no) | 2003-02-04 |
NO324426B1 true NO324426B1 (no) | 2007-10-08 |
Family
ID=27255754
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20025821A NO324426B1 (no) | 2000-06-06 | 2002-12-04 | 2-aminokarbonyl-9H-purinderivater, samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk sammensetning |
Country Status (34)
Country | Link |
---|---|
EP (1) | EP1292604B1 (ko) |
JP (2) | JP4129176B2 (ko) |
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Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7378400B2 (en) | 1999-02-01 | 2008-05-27 | University Of Virginia Patent Foundation | Method to reduce an inflammatory response from arthritis |
TWI227240B (en) * | 2000-06-06 | 2005-02-01 | Pfizer | 2-aminocarbonyl-9H-purine derivatives |
US6921753B2 (en) | 2000-06-27 | 2005-07-26 | Pfizer Inc | Purine derivatives |
US20030013675A1 (en) * | 2001-05-25 | 2003-01-16 | Boehringer Ingelheim Pharma Kg | Combination of an adenosine A2A-receptor agonist and tiotropium or a derivative thereof for treating obstructive airways and other inflammatory diseases |
WO2003029264A2 (en) | 2001-10-01 | 2003-04-10 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs having a2a agonist activity and compositions thereof |
GB0129270D0 (en) * | 2001-12-06 | 2002-01-23 | Pfizer Ltd | Pharmaceutical combination |
US6974803B2 (en) | 2001-12-06 | 2005-12-13 | Pfizer Inc | Pharmaceutical combination |
GB0129273D0 (en) * | 2001-12-06 | 2002-01-23 | Pfizer Ltd | Crystalline drug form |
ATE381336T1 (de) * | 2002-04-10 | 2008-01-15 | Univ Virginia | Verwendung von a2a adenosin rezeptor agonisten und anti-pathogene mittel enthaltenden kombinationen zur behandlung von entzündungskrankheiten |
US20060178403A1 (en) * | 2003-03-07 | 2006-08-10 | Neurocrine Biosciences, Inc. | Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto |
US7067509B2 (en) | 2003-03-07 | 2006-06-27 | Neurocrine Biosciences, Inc. | Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto |
AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
JP2007509180A (ja) | 2003-10-21 | 2007-04-12 | インスパイアー ファーマシューティカルズ,インコーポレイティド | 疼痛を治療するための、非ヌクレオチド組成物および方法 |
US7749981B2 (en) | 2003-10-21 | 2010-07-06 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with non-nucleotide P2Y12 receptor antagonist compound |
US7335648B2 (en) | 2003-10-21 | 2008-02-26 | Inspire Pharmaceuticals, Inc. | Non-nucleotide composition and method for inhibiting platelet aggregation |
ATE469157T1 (de) | 2003-10-21 | 2010-06-15 | Inspire Pharmaceuticals Inc | Tetrahydrofuroä3,4-düdioxolverbindungen und zusammensetzungen und verfahren zur inhibierung der trombozytenaggregation |
GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
EP1778712B1 (en) | 2004-08-02 | 2013-01-30 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs with modified 5'-ribose groups having a2a agonist activity |
WO2006023272A1 (en) | 2004-08-02 | 2006-03-02 | University Of Virginia Patent Foundation | 2-polycyclic propynyl adenosine analogs having a2a agonist activity |
GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
US7932376B2 (en) | 2005-05-05 | 2011-04-26 | Inspire Pharmaceuticals, Inc. | Pyrimidine-based non-nucleotide composition and method for inhibiting platelet aggregation |
GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
US7910708B2 (en) | 2005-10-21 | 2011-03-22 | Novartis Ag | Anti-IL13 human antibodies |
GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
KR20080110925A (ko) | 2006-04-21 | 2008-12-19 | 노파르티스 아게 | 아데노신 a2a 수용체 효능제로서 사용하기 위한 퓨린 유도체 |
DE602007013441D1 (de) | 2006-09-29 | 2011-05-05 | Novartis Ag | Pyrazolopyrimidine als pi3k-lipidkinasehemmer |
CA2667962A1 (en) | 2006-10-30 | 2008-05-08 | Novartis Ag | Heterocyclic compounds as antiinflammatory agents |
PL2231642T3 (pl) | 2008-01-11 | 2014-04-30 | Novartis Ag | Pirymidyny jako inhibitory kinazy |
GEP20135957B (en) | 2008-06-19 | 2013-11-11 | Takeda Pharmaceuticals Co | Heterocyclic compound and usage thereof |
PT2391366E (pt) | 2009-01-29 | 2013-02-05 | Novartis Ag | Benzimidazoles substituídos para o tratamento de astrocitomas |
EP2435462A1 (en) | 2009-05-29 | 2012-04-04 | Pfizer Limited | Novel glucocorticoid receptor agonists |
US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
EP2464649A1 (en) | 2009-08-12 | 2012-06-20 | Novartis AG | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
NZ598220A (en) | 2009-08-17 | 2014-02-28 | Intellikine Llc | Heterocyclic compounds and uses thereof |
CA2771432A1 (en) | 2009-08-20 | 2011-02-24 | Novartis Ag | Heterocyclic oxime compounds |
UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
JP2014505088A (ja) | 2011-02-10 | 2014-02-27 | ノバルティス アーゲー | C−METチロシンキナーゼ阻害剤としての[1,2,4]トリアゾロ[4,3−b]ピリダジン化合物 |
JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン, エルエルシー | 複素環化合物およびその使用 |
US9102671B2 (en) | 2011-02-25 | 2015-08-11 | Novartis Ag | Compounds and compositions as TRK inhibitors |
UY34329A (es) | 2011-09-15 | 2013-04-30 | Novartis Ag | Compuestos de triazolopiridina |
US9174994B2 (en) | 2011-11-23 | 2015-11-03 | Intellikine, Llc | Enhanced treatment regimens using mTor inhibitors |
CN104245701A (zh) | 2012-04-03 | 2014-12-24 | 诺华有限公司 | 有酪氨酸激酶抑制剂的组合产品和其应用 |
EP2968340A4 (en) | 2013-03-15 | 2016-08-10 | Intellikine Llc | COMBINING KINASE INHIBITORS AND USES THEREOF |
TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Mdm2抑制劑與BRAF抑制劑之組合及其用途 |
WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
KR20170036037A (ko) | 2014-07-31 | 2017-03-31 | 노파르티스 아게 | 조합 요법 |
TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR9914526A (pt) * | 1998-10-16 | 2001-07-03 | Pfizer | Derivados de adenina |
GB9913932D0 (en) * | 1999-06-15 | 1999-08-18 | Pfizer Ltd | Purine derivatives |
TWI227240B (en) * | 2000-06-06 | 2005-02-01 | Pfizer | 2-aminocarbonyl-9H-purine derivatives |
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