AU2006226084B2 - 2,3-substituted fused pyrimidin-4(3H)-ones as VR1 antagonists - Google Patents
2,3-substituted fused pyrimidin-4(3H)-ones as VR1 antagonists Download PDFInfo
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- AU2006226084B2 AU2006226084B2 AU2006226084A AU2006226084A AU2006226084B2 AU 2006226084 B2 AU2006226084 B2 AU 2006226084B2 AU 2006226084 A AU2006226084 A AU 2006226084A AU 2006226084 A AU2006226084 A AU 2006226084A AU 2006226084 B2 AU2006226084 B2 AU 2006226084B2
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- Prior art keywords
- pain
- alkyl
- membered heteroaromatic
- alkoxy
- heteroaromatic ring
- 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.)
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- 239000005557 antagonist Substances 0.000 title abstract description 16
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- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 247
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- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 38
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 37
- 150000002367 halogens Chemical class 0.000 claims abstract description 37
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 32
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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Landscapes
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- Psychiatry (AREA)
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- Nutrition Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0506147.8A GB0506147D0 (en) | 2005-03-24 | 2005-03-24 | Therapeutic agents |
| GB0506147.8 | 2005-03-24 | ||
| PCT/GB2006/050060 WO2006100520A1 (en) | 2005-03-24 | 2006-03-21 | 2,3-substituted fused pyrimidin-4(3h)-ones as vr1 antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2006226084A1 AU2006226084A1 (en) | 2006-09-28 |
| AU2006226084B2 true AU2006226084B2 (en) | 2011-09-08 |
Family
ID=34566491
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2006226084A Ceased AU2006226084B2 (en) | 2005-03-24 | 2006-03-21 | 2,3-substituted fused pyrimidin-4(3H)-ones as VR1 antagonists |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20110152242A1 (https=) |
| EP (1) | EP1866310B1 (https=) |
| JP (1) | JP5097696B2 (https=) |
| AU (1) | AU2006226084B2 (https=) |
| CA (1) | CA2602395A1 (https=) |
| GB (1) | GB0506147D0 (https=) |
| WO (1) | WO2006100520A1 (https=) |
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| ME02420B (me) | 2006-09-26 | 2016-09-20 | Celgene Corp | 5-supstituirani derivati kinazolinona kao sredstva protiv raka |
| CA2668579A1 (en) * | 2006-11-06 | 2008-06-05 | Neurogen Corporation | Cis-cyclohexyl substituted pyrimidinone derivatives |
| KR20090087027A (ko) * | 2006-11-13 | 2009-08-14 | 일라이 릴리 앤드 캄파니 | 염증 질환 및 암의 치료를 위한 티에노피리미디논 |
| US7803940B2 (en) | 2006-11-24 | 2010-09-28 | Takeda Pharmaceutical Company Limited | Heteromonocyclic compound or a salt thereof having strong antihypertensive action, insulin sensitizing activity and the like production thereof and use thereof for prophylaxis or treatment of cardiovascular diseases, metabolic diseases and/or central nervous system diseases |
| WO2009096701A2 (en) | 2008-01-28 | 2009-08-06 | Amorepacific Corporation | Novel compounds, isomer thereof, or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist; and pharmaceutical compositions containing the same |
| JP5438103B2 (ja) | 2008-07-02 | 2014-03-12 | アモーレパシフィック コーポレイション | バニロイド受容体アンタゴニストとしての新規化合物、その異性体またはその薬学的に許容される塩、並びにそれを含む医薬組成物 |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| WO2010137738A1 (en) * | 2009-05-28 | 2010-12-02 | Otsuka Pharmaceutical Co., Ltd. | Heterocyclic compounds for the treatment of stress-related conditions |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| JP2013518085A (ja) | 2010-02-01 | 2013-05-20 | ノバルティス アーゲー | ＣＲＦ−１受容体アンタゴニストとしてのピラゾロ［５，１ｂ］オキサゾール誘導体 |
| JP5748777B2 (ja) | 2010-02-02 | 2015-07-15 | ノバルティス アーゲー | Ｃｒｆ受容体アンタゴニストとしてのシクロヘキシルアミド誘導体 |
| US11466017B2 (en) | 2011-03-10 | 2022-10-11 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| DK2683708T3 (da) | 2011-03-11 | 2018-01-29 | Celgene Corp | Faste former af 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidin-2,6-dion og farmaceutiske sammensætninger og anvendelser deraf |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP2892887B1 (en) | 2012-09-04 | 2020-07-15 | Celgene Corporation | Isotopologues of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl) piperidine-2-6-dione and methods of preparation thereof |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PT3052485T (pt) | 2013-10-04 | 2021-10-22 | Infinity Pharmaceuticals Inc | Compostos heterocíclicos e suas utilizações |
| MX382033B (es) | 2014-03-19 | 2025-03-13 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos para utilizarlos en el tratamiento de trastornos mediados por pi3k-gamma. |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US9957267B2 (en) | 2015-07-01 | 2018-05-01 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
| WO2017048702A1 (en) | 2015-09-14 | 2017-03-23 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| DE102015012049A1 (de) * | 2015-09-15 | 2017-03-16 | Merck Patent Gmbh | Verbindungen als ASIC-Inhibitoren und deren Verwendungen |
| WO2017156397A1 (en) * | 2016-03-11 | 2017-09-14 | Board Of Regents, The University Of Texas Sysytem | Heterocyclic inhibitors of ptpn11 |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| WO2017210134A1 (en) | 2016-05-31 | 2017-12-07 | Board Of Regents, University Of Texas System | Heterocyclic inhibitors of ptpn11 |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP3658560A4 (en) | 2017-07-25 | 2021-01-06 | Crinetics Pharmaceuticals, Inc. | SOMATOSTAT IN MODULATORS AND USES THEREOF |
| MX2020011528A (es) * | 2018-05-02 | 2021-02-09 | Navire Pharma Inc | Inhibidores heterociclicos sustituidos de ptpn11. |
| CN112601750B (zh) | 2018-08-10 | 2023-10-31 | 纳维尔制药有限公司 | Ptpn11（shp2）抑制剂 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3674786A (en) * | 1968-10-17 | 1972-07-04 | Ciba Geigy Corp | New-6-amino-4-oxo-4,5-dihydro-isothiazolo(5,4-d)pyrimidines |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL363907A1 (en) * | 2001-03-26 | 2004-11-29 | Novartis Ag | Fused pyridine derivatives for use as vanilloid receptor antagonists for treating pain. |
| WO2003014064A1 (en) * | 2001-07-31 | 2003-02-20 | Bayer Healthcare Ag | Naphthylurea and naphthylacetamide derivatives as vanilloid receptor 1 (vr1) antagonists |
| CA2545725A1 (en) * | 2003-11-14 | 2005-06-02 | Merck Sharp & Dohme Limited | Bicyclic pyrimidin-4-(3h)-ones and analogues and derivatives thereof which modulate the function of the vanilloid-1 receptor (vr1) |
| AR051596A1 (es) * | 2004-10-26 | 2007-01-24 | Irm Llc | Compuestos heterociclicos condensados nitrogenados como inhibidores de la actividad del receptor canabinoide 1; composiciones farmaceuticas que los contienen y su empleo en la preparacion de medicamentos para el tratamiento de trastornos alimentarios |
-
2005
- 2005-03-24 GB GBGB0506147.8A patent/GB0506147D0/en not_active Ceased
-
2006
- 2006-03-21 EP EP06710177A patent/EP1866310B1/en not_active Expired - Lifetime
- 2006-03-21 AU AU2006226084A patent/AU2006226084B2/en not_active Ceased
- 2006-03-21 US US11/886,812 patent/US20110152242A1/en not_active Abandoned
- 2006-03-21 JP JP2008502490A patent/JP5097696B2/ja not_active Expired - Fee Related
- 2006-03-21 WO PCT/GB2006/050060 patent/WO2006100520A1/en not_active Ceased
- 2006-03-21 CA CA002602395A patent/CA2602395A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3674786A (en) * | 1968-10-17 | 1972-07-04 | Ciba Geigy Corp | New-6-amino-4-oxo-4,5-dihydro-isothiazolo(5,4-d)pyrimidines |
Non-Patent Citations (3)
| Title |
|---|
| DAVE, C.G. et al., Journal of the Indian Chemical Society, 1989, vol. 66, pages 810-812 * |
| DING, M.-W. et al., Synthetic Communications, 2000, vol. 30, pages 1599-1604 * |
| PATHAK, U.S. et al, Indian Journal of Chemistry, 1991, vol. 30B, pages 618-619 * |
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| AU2006226084A1 (en) | 2006-09-28 |
| EP1866310B1 (en) | 2012-07-11 |
| US20110152242A1 (en) | 2011-06-23 |
| WO2006100520A1 (en) | 2006-09-28 |
| GB0506147D0 (en) | 2005-05-04 |
| EP1866310A1 (en) | 2007-12-19 |
| JP5097696B2 (ja) | 2012-12-12 |
| CA2602395A1 (en) | 2006-09-28 |
| JP2008534486A (ja) | 2008-08-28 |
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