EA018133B1 - Конденсированные пиримидиновые производные как модуляторы trpv3 - Google Patents
Конденсированные пиримидиновые производные как модуляторы trpv3 Download PDFInfo
- Publication number
- EA018133B1 EA018133B1 EA201000674A EA201000674A EA018133B1 EA 018133 B1 EA018133 B1 EA 018133B1 EA 201000674 A EA201000674 A EA 201000674A EA 201000674 A EA201000674 A EA 201000674A EA 018133 B1 EA018133 B1 EA 018133B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- pyrido
- pyrimidin
- vinyl
- phenyl
- Prior art date
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- 150000003230 pyrimidines Chemical class 0.000 title abstract description 6
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 219
- 229920002554 vinyl polymer Polymers 0.000 claims description 76
- -1 2- (cyclopentyloxy) -3-methylphenyl Chemical group 0.000 claims description 71
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 71
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 24
- 208000002193 Pain Diseases 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000001188 haloalkyl group Chemical group 0.000 claims description 14
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 6
- 125000004001 thioalkyl group Chemical group 0.000 claims description 6
- 230000006870 function Effects 0.000 claims description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- YYSAQADMDKBWCD-ISLYRVAYSA-N 2-[(e)-2-(2-cyclopentyloxy-3-methoxyphenyl)ethenyl]-3-phenylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1CCCC1OC=1C(OC)=CC=CC=1\C=C\C=1N=C2C=CC=CN2C(=O)C=1C1=CC=CC=C1 YYSAQADMDKBWCD-ISLYRVAYSA-N 0.000 claims description 3
- YQIFMLKKZUNMIL-FOCLMDBBSA-N 2-[(e)-2-[2-(cyclopropylmethoxy)-3-methoxyphenyl]ethenyl]-3-phenylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1CC1COC=1C(OC)=CC=CC=1\C=C\C=1N=C2C=CC=CN2C(=O)C=1C1=CC=CC=C1 YQIFMLKKZUNMIL-FOCLMDBBSA-N 0.000 claims description 3
- ULSLDSMNKAWCJA-WUKNDPDISA-N 4-[2-[(e)-2-(2-cyclopentyloxy-3-methoxyphenyl)ethenyl]-4-oxopyrido[1,2-a]pyrimidin-3-yl]benzonitrile Chemical compound C1CCCC1OC=1C(OC)=CC=CC=1\C=C\C=1N=C2C=CC=CN2C(=O)C=1C1=CC=C(C#N)C=C1 ULSLDSMNKAWCJA-WUKNDPDISA-N 0.000 claims description 3
- RMBXOXFAKCBYLC-WUKNDPDISA-N 4-[2-[(e)-2-(2-cyclopentyloxy-3-methoxyphenyl)ethenyl]-9-methoxy-4-oxopyrido[1,2-a]pyrimidin-3-yl]benzonitrile Chemical compound C1CCCC1OC=1C(OC)=CC=CC=1\C=C\C=1N=C2C(OC)=CC=CN2C(=O)C=1C1=CC=C(C#N)C=C1 RMBXOXFAKCBYLC-WUKNDPDISA-N 0.000 claims description 3
- 208000006820 Arthralgia Diseases 0.000 claims description 3
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- 102000011040 TRPV Cation Channels Human genes 0.000 claims description 3
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims description 2
- VIKIMOKNEKYFBO-OUKQBFOZSA-N 2-[(e)-2-(2-cyclopentyloxy-3-methoxyphenyl)ethenyl]-3-pyridin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1CCCC1OC=1C(OC)=CC=CC=1\C=C\C=1N=C2C=CC=CN2C(=O)C=1C1=CC=NC=C1 VIKIMOKNEKYFBO-OUKQBFOZSA-N 0.000 claims description 2
- VAKQBHALQXEEAG-UHFFFAOYSA-N 2-phenylpyrido[1,2-a]pyrimidin-4-one Chemical compound N1=C2C=CC=CN2C(=O)C=C1C1=CC=CC=C1 VAKQBHALQXEEAG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
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- 201000004624 Dermatitis Diseases 0.000 claims description 2
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- 230000000172 allergic effect Effects 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- 231100000360 alopecia Toxicity 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
- 230000003925 brain function Effects 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- NYJWYCAHJRGKMI-UHFFFAOYSA-N pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC=CN2C(=O)C=CN=C21 NYJWYCAHJRGKMI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
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- FDPXDKXERHFWRM-DTQAZKPQSA-N 2-[(e)-2-(2-butoxy-3-methoxyphenyl)ethenyl]-3-[4-(trifluoromethoxy)phenyl]pyrido[1,2-a]pyrimidin-4-one Chemical compound CCCCOC1=C(OC)C=CC=C1\C=C\C1=C(C=2C=CC(OC(F)(F)F)=CC=2)C(=O)N2C=CC=CC2=N1 FDPXDKXERHFWRM-DTQAZKPQSA-N 0.000 claims 1
- NMLRAVMTQIFDMO-WUKNDPDISA-N 4-[2-[(e)-2-(3-methoxy-2-pentoxyphenyl)ethenyl]-4-oxopyrido[1,2-a]pyrimidin-3-yl]benzonitrile Chemical compound CCCCCOC1=C(OC)C=CC=C1\C=C\C1=C(C=2C=CC(=CC=2)C#N)C(=O)N2C=CC=CC2=N1 NMLRAVMTQIFDMO-WUKNDPDISA-N 0.000 claims 1
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- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
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Applications Claiming Priority (6)
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| IN82MU2008 | 2008-01-11 | ||
| US2877008P | 2008-02-14 | 2008-02-14 | |
| IN548MU2008 | 2008-03-18 | ||
| IN798MU2008 | 2008-04-04 | ||
| US4827608P | 2008-04-28 | 2008-04-28 | |
| PCT/IN2009/000025 WO2009109987A2 (en) | 2008-01-11 | 2009-01-07 | Fused pyrimidine derivatives as trpv3 modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201000674A1 EA201000674A1 (ru) | 2011-02-28 |
| EA018133B1 true EA018133B1 (ru) | 2013-05-30 |
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| EA201000674A EA018133B1 (ru) | 2008-01-11 | 2009-01-07 | Конденсированные пиримидиновые производные как модуляторы trpv3 |
Country Status (10)
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| US (1) | US8349846B2 (enExample) |
| EP (1) | EP2229388A4 (enExample) |
| JP (1) | JP5419894B2 (enExample) |
| AU (1) | AU2009220825A1 (enExample) |
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| EA (1) | EA018133B1 (enExample) |
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| MX (1) | MX2010005769A (enExample) |
| NZ (1) | NZ595781A (enExample) |
| WO (1) | WO2009109987A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8119647B2 (en) * | 2008-04-23 | 2012-02-21 | Glenmark Pharmaceuticals S.A. | Fused pyrimidineone compounds as TRPV3 modulators |
| GEP20146096B (en) * | 2008-12-26 | 2014-05-27 | Glenmark Pharmaceuticals Sa | Fused imidazole derivatives as trpv3 antagonists |
| NZ702135A (en) * | 2012-04-23 | 2016-09-30 | Genentech Inc | Intermediates and processes for preparing 5-bromo-4-chloro-3-nitro-1h-pyrrolo[2,3-b]pyridine |
| WO2021108404A1 (en) | 2019-11-25 | 2021-06-03 | Amgen Inc. | Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3907798A (en) * | 1966-06-15 | 1975-09-23 | Sterling Drug Inc | Preparation of 4H-pyrido{8 1,2-a{9 pyrimidin-4-ones from cyclic alkylidene 2-pyridylaminomethylenemalonates |
| US3960863A (en) * | 1974-06-25 | 1976-06-01 | Sankyo Company Limited | Pyrido[1,2-a]pyrimidinone derivatives |
| GB1454312A (en) * | 1973-03-30 | 1976-11-03 | Chinoin Gyogyszer Es Vegyeszet | 4-oxo-6,7,8,9-tetrahydropyrido-1,2-a-pyrimidine derivatives methods for their preparation and compositions containing them |
| US5252572A (en) * | 1988-02-03 | 1993-10-12 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. | Pyridopyrimidine derivatives, pharmaceutical compositions containing them and process for preparing same |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4223031A (en) | 1978-05-05 | 1980-09-16 | Mead Johnson & Company | Azolopyrimidinones |
| US4310526A (en) * | 1979-05-08 | 1982-01-12 | Farmitalia Carlo Erba S.P.A. | Substituted 6,7-methylene pyrido[1,2-a]pyrimidines useful as anti-allergic and anti-ulcer agents |
| NL8202706A (nl) | 1981-07-15 | 1983-02-01 | Erba Farmitalia | Gesubstitueerde thiazolo3,2-apyrimidinen en werkwijzen ter bereiding ervan. |
| US4537962A (en) | 1982-02-04 | 1985-08-27 | Farmitalia Carlo Erba, S.P.A. | Substituted 1,3,4-thiadiazolo[3,2-A]pyrimidines and compositions containing them |
| GB8300728D0 (en) | 1983-01-12 | 1983-02-16 | Erba Farmitalia | Substituted carboxy-thiazolo / 3 2 - a / pyrimidine derivatives |
| US5204352A (en) | 1987-09-29 | 1993-04-20 | The United States Of America As Represented By The Secretary Of The Army | Compounds exhibiting anti-parasitic activity and a method for their use |
| IT1263804B (it) | 1993-01-22 | 1996-09-03 | Luso Farmaco Inst | Derivati pirimidinonici fusi con eterocicli azotati ad attivita' a ii antagonista |
| DE69526822T2 (de) | 1994-02-23 | 2003-01-23 | Kyowa Hakko Kogyo K.K., Tokio/Tokyo | Xanthin-derivate |
| JPH07242666A (ja) | 1994-03-08 | 1995-09-19 | Fujisawa Pharmaceut Co Ltd | 複素環化合物 |
| US6323208B1 (en) | 1997-09-05 | 2001-11-27 | Pfizer Inc | Atropisomers of 2,3-disubstituted-(5.6)-heteroaryl fused-pyrimidin-4-ones |
| JP2001522853A (ja) | 1997-11-11 | 2001-11-20 | ファイザー・プロダクツ・インク | 抗癌剤として有用なチエノピリミジンおよびチエノピリジン誘導体 |
| US6559145B2 (en) | 2000-07-12 | 2003-05-06 | Pharmacia & Upjohn Company | Heterocycle carboxamides as antiviral agents |
| RU2003130221A (ru) * | 2001-03-26 | 2005-04-10 | Новартис АГ (CH) | Сконденсированные пиридиновые производные, предназначенные для применения в качестве антагонистов ваниллоидного рецептора при лечении боли |
| US20070135454A1 (en) * | 2003-11-14 | 2007-06-14 | Tracy Bayliss | Bicyclic pyrimidin-4(3h)-ones and analogues and derivatives thereof which modulate the function of the vanilloid-1-receptor(vr1) |
| BRPI0512360A (pt) | 2004-06-23 | 2008-03-11 | Idenix Cayman Ltd | derivados de 5-aza-7-deazapurina para o tratamento de flaviviridae |
| DE502004004687D1 (de) | 2004-08-18 | 2007-09-27 | Robert Boettcher | Einschraubbares enossales dentalimplantat |
| WO2006028963A2 (en) | 2004-09-03 | 2006-03-16 | Celgene Corporation | Substituted heterocyclic compounds and uses thereof |
| US20060128710A1 (en) * | 2004-12-09 | 2006-06-15 | Chih-Hung Lee | Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof |
| CA2589363A1 (en) | 2004-12-13 | 2006-06-22 | Eli Lilly And Company | Spiro derivatives as lipoxygenase inhibitors |
| US20080220968A1 (en) | 2005-07-05 | 2008-09-11 | Ge Healthcare Bio-Sciences Ab | [1, 2, 4] Triazolo [1, 5-A] Pyrimidine Derivatives as Chromatographic Adsorbent for the Selective Adsorption of Igg |
| KR20080064972A (ko) | 2005-10-07 | 2008-07-10 | 그렌마크 파머수티칼스 에스. 아. | 치환된 벤조융합 유도체 및 이의 바닐로이드 수용체리간드로서의 용도 |
| EP1954283A2 (en) | 2005-11-04 | 2008-08-13 | Hydra Biosciences, Inc. | Compounds for modulating trpv3 function |
| GB0525069D0 (en) * | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| TW201900217A (zh) | 2005-12-22 | 2019-01-01 | 美商海卓勒生物科學公司 | 用於調節ｔｒｐａ１功能之化合物 |
| US8980954B2 (en) | 2006-04-25 | 2015-03-17 | Stc.Unm | Substituted cis- and trans-stilbenes as therapeutic agents |
| WO2008001101A2 (en) | 2006-06-29 | 2008-01-03 | Astex Therapeutics Limited | Pharmaceutical combinations |
| WO2008012010A1 (en) | 2006-07-27 | 2008-01-31 | Ucb Pharma, S.A. | Fused oxazoles & thiazoles as histamine h3- receptor ligands |
| MX2009008338A (es) | 2007-02-05 | 2009-08-12 | Xenon Pharmaceuticals Inc | Compuestos de piridopirimidinona de utilidad en el tratamiento de enfermedades o condiciones patologicas mediadas por los canales de sodio. |
-
2009
- 2009-01-07 JP JP2010541889A patent/JP5419894B2/ja not_active Expired - Fee Related
- 2009-01-07 CA CA2724008A patent/CA2724008A1/en not_active Abandoned
- 2009-01-07 US US12/811,975 patent/US8349846B2/en not_active Expired - Fee Related
- 2009-01-07 WO PCT/IN2009/000025 patent/WO2009109987A2/en not_active Ceased
- 2009-01-07 AU AU2009220825A patent/AU2009220825A1/en not_active Abandoned
- 2009-01-07 EA EA201000674A patent/EA018133B1/ru not_active IP Right Cessation
- 2009-01-07 EP EP09717522A patent/EP2229388A4/en not_active Withdrawn
- 2009-01-07 NZ NZ595781A patent/NZ595781A/xx not_active IP Right Cessation
- 2009-01-07 GE GEAP200911911A patent/GEP20125574B/en unknown
- 2009-01-07 MX MX2010005769A patent/MX2010005769A/es active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3907798A (en) * | 1966-06-15 | 1975-09-23 | Sterling Drug Inc | Preparation of 4H-pyrido{8 1,2-a{9 pyrimidin-4-ones from cyclic alkylidene 2-pyridylaminomethylenemalonates |
| GB1454312A (en) * | 1973-03-30 | 1976-11-03 | Chinoin Gyogyszer Es Vegyeszet | 4-oxo-6,7,8,9-tetrahydropyrido-1,2-a-pyrimidine derivatives methods for their preparation and compositions containing them |
| US3960863A (en) * | 1974-06-25 | 1976-06-01 | Sankyo Company Limited | Pyrido[1,2-a]pyrimidinone derivatives |
| US5252572A (en) * | 1988-02-03 | 1993-10-12 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. | Pyridopyrimidine derivatives, pharmaceutical compositions containing them and process for preparing same |
Non-Patent Citations (1)
| Title |
|---|
| Djekou, Serge; Gellis, Armand; Maldonado, Jose; Crozet, Michel P.;Vanelle, Patrice. "A radical synthetic approach to the new potentially bioactive pyrimidinones." Heterocycles (2001), 55(3), 535-544 *table, schemes* * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5419894B2 (ja) | 2014-02-19 |
| JP2011509288A (ja) | 2011-03-24 |
| EA201000674A1 (ru) | 2011-02-28 |
| GEP20125574B (en) | 2012-07-10 |
| NZ595781A (en) | 2013-07-26 |
| AU2009220825A1 (en) | 2012-01-19 |
| MX2010005769A (es) | 2010-11-12 |
| CA2724008A1 (en) | 2009-09-11 |
| WO2009109987A2 (en) | 2009-09-11 |
| US8349846B2 (en) | 2013-01-08 |
| AU2009220825A2 (en) | 2012-04-19 |
| WO2009109987A3 (en) | 2009-12-17 |
| EP2229388A2 (en) | 2010-09-22 |
| US20100292254A1 (en) | 2010-11-18 |
| EP2229388A4 (en) | 2012-03-07 |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |