RU2296764C2 - Производные нафтиридина, способ их получения и применение - Google Patents
Производные нафтиридина, способ их получения и применение Download PDFInfo
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- RU2296764C2 RU2296764C2 RU2004117169/04A RU2004117169A RU2296764C2 RU 2296764 C2 RU2296764 C2 RU 2296764C2 RU 2004117169/04 A RU2004117169/04 A RU 2004117169/04A RU 2004117169 A RU2004117169 A RU 2004117169A RU 2296764 C2 RU2296764 C2 RU 2296764C2
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- formula
- naphthyridin
- compound
- compounds
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 150000005054 naphthyridines Chemical class 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 19
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 13
- 230000000414 obstructive effect Effects 0.000 claims abstract description 12
- 108010044467 Isoenzymes Proteins 0.000 claims abstract description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- -1 cyano, carboxyl Chemical group 0.000 claims description 42
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims description 15
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 210000002345 respiratory system Anatomy 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 5
- TWWNJXWEOLLKJT-UHFFFAOYSA-N 4-[8-(3-cyanophenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1C1=CC2=CC=CN=C2C(C=2C=C(C=CC=2)C#N)=N1 TWWNJXWEOLLKJT-UHFFFAOYSA-N 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 5
- 125000006413 ring segment Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
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- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- NMPRJSCSBOKQRT-UHFFFAOYSA-N 4-[8-(5-fluoro-2-methoxyphenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylic acid Chemical compound COC1=CC=C(F)C=C1C1=NC(C2CCC(CC2)C(O)=O)=CC2=CC=CN=C12 NMPRJSCSBOKQRT-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
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- 238000002955 isolation Methods 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 claims 2
- HVRZNNIVIAZQQK-UHFFFAOYSA-N CCC(CC1)(CCC1C1=NC(C2=CC(C#N)=CC=C2)=C2N=CC=CC2=C1)C(O)=O Chemical compound CCC(CC1)(CCC1C1=NC(C2=CC(C#N)=CC=C2)=C2N=CC=CC2=C1)C(O)=O HVRZNNIVIAZQQK-UHFFFAOYSA-N 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 14
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- 239000000203 mixture Substances 0.000 description 39
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
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- 230000005764 inhibitory process Effects 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
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- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
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- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
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| GB0126511.5 | 2001-11-05 | ||
| GB0126511A GB0126511D0 (en) | 2001-11-05 | 2001-11-05 | Organic compounds |
| GB0209882.0 | 2002-04-30 | ||
| GB0209882A GB0209882D0 (en) | 2002-04-30 | 2002-04-30 | Organic compounds |
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| RU2004117169A RU2004117169A (ru) | 2006-01-10 |
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| RU2004117169/04A RU2296764C2 (ru) | 2001-11-05 | 2002-11-04 | Производные нафтиридина, способ их получения и применение |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2470932C2 (ru) * | 2007-02-27 | 2012-12-27 | Байер Шеринг Фарма Акциенгезельшафт | Замещенные 4-арил-1,4-дигидро-1,6-нафтиридинамиды и их применение |
| RU2470932C9 (ru) * | 2007-02-27 | 2013-06-27 | Байер Шеринг Фарма Акциенгезельшафт | Замещенные 4-арил-1,4-дигидро-1,6-нафтиридинамиды и их применение |
| RU2692775C2 (ru) * | 2014-09-26 | 2019-06-27 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Производные нафтиридина в качестве антагонистов альфа v бета 6 интегрина для лечения, в частности, фиброзных заболеваний |
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| ES2251866B1 (es) * | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251867B1 (es) * | 2004-06-21 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
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| EP2968340A4 (en) | 2013-03-15 | 2016-08-10 | Intellikine Llc | COMBINING KINASE INHIBITORS AND USES THEREOF |
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| JP6713982B2 (ja) | 2014-07-24 | 2020-06-24 | ファイザー・インク | ピラゾロピリミジン化合物 |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
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| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
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| CN113423435A (zh) | 2018-12-28 | 2021-09-21 | 雷杰纳荣制药公司 | 使用花生四烯酸15-脂氧合酶(alox15)抑制剂治疗呼吸系统病症 |
| EP3980121A1 (en) | 2019-06-10 | 2022-04-13 | Novartis AG | Pyridine and pyrazine derivative for the treatment of cf, copd, and bronchiectasis |
| CN110339192A (zh) * | 2019-08-22 | 2019-10-18 | 吉林大学 | 一种掌叶防己碱用于治疗急性肺损伤的实验方法 |
| AU2020338971B2 (en) | 2019-08-28 | 2023-11-23 | Novartis Ag | Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease |
| EP3805206A1 (en) * | 2019-10-08 | 2021-04-14 | Novaled GmbH | Compound and an organic semiconducting layer, an organic electronic device, a display device and a lighting device comprising the same |
| 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 |
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| FR2625743A1 (fr) * | 1988-01-08 | 1989-07-13 | Sandoz Sa | Derives d'isoquinoleine, leur preparation et leur utilisation |
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| WO1998018796A1 (en) * | 1996-10-28 | 1998-05-07 | Novartis Ag | Naphthyridine derivatives |
| RU2174123C2 (ru) * | 1996-10-28 | 2001-09-27 | Новартис Аг | Производные 8-арил-1,7-нафтиридина и фармацевтическая композиция, обладающая противовоспалительной активностью |
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| IE903911A1 (en) * | 1989-11-20 | 1991-05-22 | Ici Plc | Diazine derivatives |
| WO1999018077A1 (en) | 1997-10-02 | 1999-04-15 | Eisai Co., Ltd. | Fused pyridine derivatives |
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2002
- 2002-11-01 AR ARP020104187A patent/AR037517A1/es unknown
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- 2002-11-04 JP JP2003541835A patent/JP4150672B2/ja not_active Expired - Lifetime
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- 2002-11-04 HU HU0402311A patent/HUP0402311A3/hu unknown
- 2002-11-04 BR BR0213877-8A patent/BR0213877A/pt not_active Application Discontinuation
- 2002-11-04 PE PE2002001073A patent/PE20030535A1/es not_active Application Discontinuation
- 2002-11-04 PT PT02787554T patent/PT1443925E/pt unknown
- 2002-11-04 RU RU2004117169/04A patent/RU2296764C2/ru not_active IP Right Cessation
- 2002-11-04 AT AT02787554T patent/ATE349209T1/de active
- 2002-11-04 CA CA2462211A patent/CA2462211C/en not_active Expired - Lifetime
- 2002-11-04 ES ES02787554T patent/ES2275935T3/es not_active Expired - Lifetime
- 2002-11-04 KR KR1020047006772A patent/KR100623548B1/ko not_active Expired - Fee Related
- 2002-11-04 PL PL02368286A patent/PL368286A1/xx not_active Application Discontinuation
- 2002-11-04 CN CNB028214897A patent/CN1298324C/zh not_active Expired - Lifetime
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2004
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- 2004-05-21 NO NO20042097A patent/NO329093B1/no not_active IP Right Cessation
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2007
- 2007-03-06 CY CY20071100316T patent/CY1107532T1/el unknown
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| FR2625743A1 (fr) * | 1988-01-08 | 1989-07-13 | Sandoz Sa | Derives d'isoquinoleine, leur preparation et leur utilisation |
| US5466697A (en) * | 1994-07-13 | 1995-11-14 | Syntex (U.S.A.) Inc. | 8-phenyl-1,6-naphthyridin-5-ones |
| WO1998018796A1 (en) * | 1996-10-28 | 1998-05-07 | Novartis Ag | Naphthyridine derivatives |
| RU2174123C2 (ru) * | 1996-10-28 | 2001-09-27 | Новартис Аг | Производные 8-арил-1,7-нафтиридина и фармацевтическая композиция, обладающая противовоспалительной активностью |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2470932C2 (ru) * | 2007-02-27 | 2012-12-27 | Байер Шеринг Фарма Акциенгезельшафт | Замещенные 4-арил-1,4-дигидро-1,6-нафтиридинамиды и их применение |
| RU2470932C9 (ru) * | 2007-02-27 | 2013-06-27 | Байер Шеринг Фарма Акциенгезельшафт | Замещенные 4-арил-1,4-дигидро-1,6-нафтиридинамиды и их применение |
| RU2692775C2 (ru) * | 2014-09-26 | 2019-06-27 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Производные нафтиридина в качестве антагонистов альфа v бета 6 интегрина для лечения, в частности, фиброзных заболеваний |
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