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)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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)
| Country | Link |
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| US (1) | US8349846B2 (enExample) |
| EP (1) | EP2229388A4 (enExample) |
| JP (1) | JP5419894B2 (enExample) |
| AU (1) | AU2009220825A1 (enExample) |
| CA (1) | CA2724008A1 (enExample) |
| EA (1) | EA018133B1 (enExample) |
| GE (1) | GEP20125574B (enExample) |
| MX (1) | MX2010005769A (enExample) |
| NZ (1) | NZ595781A (enExample) |
| WO (1) | WO2009109987A2 (enExample) |
Families Citing this family (4)
| 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 |
| NZ595775A (en) | 2008-12-26 | 2013-07-26 | Glenmark Pharmaceuticals Sa | Fused imidazole derivatives as trpv3 antagonist |
| RU2635359C2 (ru) * | 2012-04-23 | 2017-11-13 | Дженентек Инк. | Промежуточные химические соединения и способы получения соединений |
| MX2022006370A (es) | 2019-11-25 | 2022-09-07 | Amgen Inc | Compuestos heterocíclicos como inhibidores de delta-5 desaturasa y métodos de uso. |
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 |
| IL59802A (en) * | 1979-05-08 | 1983-07-31 | Erba Farmitalia | Substituted pyrido(1,2-a)pyrimidine carboxylic acid derivatives,their preparation and pharmaceutical compositions containing them |
| 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 |
| WO1995023148A1 (en) | 1994-02-23 | 1995-08-31 | Kyowa Hakko Kogyo Co., Ltd. | Xanthine derivative |
| 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 |
| SK6652000A3 (en) | 1997-11-11 | 2002-05-09 | Pfizer Prod Inc | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
| US6559145B2 (en) | 2000-07-12 | 2003-05-06 | Pharmacia & Upjohn Company | Heterocycle carboxamides as antiviral agents |
| CZ20032561A3 (cs) * | 2001-03-26 | 2003-12-17 | Novartis Ag | Deriváty pyridinu, způsob jejich přípravy a farmaceutický prostředek, který je obsahuje |
| EP1687306A1 (en) * | 2003-11-14 | 2006-08-09 | MERCK SHARP & DOHME LTD. | Bicyclic pyrimidin-4-(3h)-ones and analogues and derivatives thereof which modulate the function of the vanilloid-1 receptor (vr1) |
| US20060040944A1 (en) | 2004-06-23 | 2006-02-23 | Gilles Gosselin | 5-Aza-7-deazapurine derivatives for treating Flaviviridae |
| JP4448170B2 (ja) | 2004-08-18 | 2010-04-07 | ベッチャー・ローベルト | エノサル歯科インプラント |
| 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 |
| EP1931681B1 (en) | 2005-10-07 | 2012-11-14 | Glenmark Pharmaceuticals S.A. | Substituted benzofused derivatives and their use as vanilloid receptor ligands |
| US20100152209A1 (en) | 2005-11-04 | 2010-06-17 | Hydra Biosciences Inc. | Compounds for Modulating TRPV3 Function |
| GB0525069D0 (en) * | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| EP1962855B1 (en) | 2005-12-22 | 2013-08-21 | Hydra Biosciences, Inc. | Trpa1 inhibitors for treating pain |
| US8980954B2 (en) | 2006-04-25 | 2015-03-17 | Stc.Unm | Substituted cis- and trans-stilbenes as therapeutic agents |
| JP2009542608A (ja) | 2006-06-29 | 2009-12-03 | アステックス・セラピューティクス・リミテッド | 医薬組合せ剤 |
| WO2008012010A1 (en) | 2006-07-27 | 2008-01-31 | Ucb Pharma, S.A. | Fused oxazoles & thiazoles as histamine h3- receptor ligands |
| CA2677493A1 (en) | 2007-02-05 | 2008-08-14 | Xenon Pharmaceuticals Inc. | Pyridopyrimidinone compounds useful in treating sodium channel-mediated diseases or conditions |
-
2009
- 2009-01-07 GE GEAP200911911A patent/GEP20125574B/en unknown
- 2009-01-07 JP JP2010541889A patent/JP5419894B2/ja not_active Expired - Fee Related
- 2009-01-07 WO PCT/IN2009/000025 patent/WO2009109987A2/en not_active Ceased
- 2009-01-07 EP EP09717522A patent/EP2229388A4/en not_active Withdrawn
- 2009-01-07 US US12/811,975 patent/US8349846B2/en not_active Expired - Fee Related
- 2009-01-07 MX MX2010005769A patent/MX2010005769A/es active IP Right Grant
- 2009-01-07 NZ NZ595781A patent/NZ595781A/xx not_active IP Right Cessation
- 2009-01-07 CA CA2724008A patent/CA2724008A1/en not_active Abandoned
- 2009-01-07 AU AU2009220825A patent/AU2009220825A1/en not_active Abandoned
- 2009-01-07 EA EA201000674A patent/EA018133B1/ru not_active IP Right Cessation
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 |
|---|---|
| MX2010005769A (es) | 2010-11-12 |
| GEP20125574B (en) | 2012-07-10 |
| AU2009220825A2 (en) | 2012-04-19 |
| EA201000674A1 (ru) | 2011-02-28 |
| US8349846B2 (en) | 2013-01-08 |
| NZ595781A (en) | 2013-07-26 |
| EP2229388A2 (en) | 2010-09-22 |
| JP2011509288A (ja) | 2011-03-24 |
| CA2724008A1 (en) | 2009-09-11 |
| WO2009109987A3 (en) | 2009-12-17 |
| AU2009220825A1 (en) | 2012-01-19 |
| JP5419894B2 (ja) | 2014-02-19 |
| US20100292254A1 (en) | 2010-11-18 |
| EP2229388A4 (en) | 2012-03-07 |
| WO2009109987A2 (en) | 2009-09-11 |
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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 |