MX2014005935A - Tieno- y furo-pirimidinas y piridinas, utiles como inhibidores del canal de potasio. - Google Patents
Tieno- y furo-pirimidinas y piridinas, utiles como inhibidores del canal de potasio.Info
- Publication number
- MX2014005935A MX2014005935A MX2014005935A MX2014005935A MX2014005935A MX 2014005935 A MX2014005935 A MX 2014005935A MX 2014005935 A MX2014005935 A MX 2014005935A MX 2014005935 A MX2014005935 A MX 2014005935A MX 2014005935 A MX2014005935 A MX 2014005935A
- Authority
- MX
- Mexico
- Prior art keywords
- optionally substituted
- 6alkyl
- thieno
- pyrimidin
- phenyl
- Prior art date
Links
- 102000004257 Potassium Channel Human genes 0.000 title abstract description 20
- 239000003112 inhibitor Substances 0.000 title abstract description 20
- 108020001213 potassium channel Proteins 0.000 title abstract description 20
- 150000003222 pyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 330
- 102100033063 G protein-activated inward rectifier potassium channel 1 Human genes 0.000 claims abstract description 61
- 101000944266 Homo sapiens G protein-activated inward rectifier potassium channel 1 Proteins 0.000 claims abstract description 61
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- 101000614712 Homo sapiens G protein-activated inward rectifier potassium channel 4 Proteins 0.000 claims abstract description 55
- 102100021237 G protein-activated inward rectifier potassium channel 4 Human genes 0.000 claims abstract description 54
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 154
- 238000000034 method Methods 0.000 claims description 139
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- 125000002757 morpholinyl group Chemical group 0.000 claims description 33
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 32
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- DENZKSMZADASCI-UHFFFAOYSA-N tert-butyl n-[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C1=NC=NC2=C1C(C=1C=CC=CC=1)=CS2 DENZKSMZADASCI-UHFFFAOYSA-N 0.000 claims description 2
- NESAZZCPNCLODA-UHFFFAOYSA-N tert-butyl n-[1-(6-methyl-5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-yl]carbamate Chemical compound C=12C(C=3C=CC=CC=3)=C(C)SC2=NC=NC=1N1CCC(NC(=O)OC(C)(C)C)CC1 NESAZZCPNCLODA-UHFFFAOYSA-N 0.000 claims description 2
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- WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical compound C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
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- HDPGSWMTDGGUEB-UHFFFAOYSA-N tert-butyl 5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1C(O)C2 HDPGSWMTDGGUEB-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
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- SMZMHUCIDGHERP-UHFFFAOYSA-N thieno[2,3-b]pyridine Chemical group C1=CN=C2SC=CC2=C1 SMZMHUCIDGHERP-UHFFFAOYSA-N 0.000 description 1
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- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Cardiology (AREA)
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- Endocrinology (AREA)
- Epidemiology (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1119703.5A GB201119703D0 (en) | 2011-11-15 | 2011-11-15 | Compounds |
| GBGB1214250.1A GB201214250D0 (en) | 2012-08-09 | 2012-08-09 | Compounds |
| PCT/GB2012/052842 WO2013072694A1 (en) | 2011-11-15 | 2012-11-15 | Thieno- and furo - pyrimidines and pyridines, useful as potassium channel inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2014005935A true MX2014005935A (es) | 2014-09-04 |
Family
ID=47222145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2014005935A MX2014005935A (es) | 2011-11-15 | 2012-11-15 | Tieno- y furo-pirimidinas y piridinas, utiles como inhibidores del canal de potasio. |
Country Status (15)
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SMT201800306T1 (it) | 2013-06-06 | 2018-07-17 | Astellas Pharma Inc | Composto di benzotiofene |
| FR3015483B1 (fr) * | 2013-12-23 | 2016-01-01 | Servier Lab | Nouveaux derives de thienopyrimidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| RU2545758C1 (ru) * | 2014-03-20 | 2015-04-10 | Общество с ограниченной ответственностью "Алион" | Бициклические пиримидины или их фармацевтически приемлемые соли-активаторы антиоксидантной программы и их применение в качестве цитопротекторов |
| USRE49687E1 (en) | 2014-09-09 | 2023-10-10 | The Regents Of The University Of Michigan | Thienopyrimidine and thienopyridine compounds and methods of use thereof |
| AR104020A1 (es) | 2015-06-04 | 2017-06-21 | Kura Oncology Inc | Métodos y composiciones para inhibir la interacción de menina con proteínas mill |
| US10588907B2 (en) | 2015-06-04 | 2020-03-17 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with MLL proteins |
| FR3037956B1 (fr) * | 2015-06-23 | 2017-08-04 | Servier Lab | Nouveaux derives d'acide amine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3037957B1 (fr) * | 2015-06-23 | 2019-01-25 | Les Laboratoires Servier | Nouveaux derives d'hydroxyester, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3037959B1 (fr) * | 2015-06-23 | 2017-08-04 | Servier Lab | Nouveaux derives bicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR3037958B1 (fr) * | 2015-06-23 | 2019-01-25 | Les Laboratoires Servier | Nouveaux derives d'hydroxy-acide, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP3394056B1 (en) | 2015-12-22 | 2021-04-14 | Shy Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| CN109640987B (zh) | 2016-03-16 | 2022-12-02 | 库拉肿瘤学公司 | Menin-mll的桥联双环抑制剂及使用方法 |
| LT3429591T (lt) * | 2016-03-16 | 2023-07-10 | Kura Oncology, Inc. | Pakeistojo tieno[2,3-d]pirimidino dariniai kaip menino-mll inhibitoriai ir jų panaudojimo būdai |
| CN106727587A (zh) * | 2016-11-28 | 2017-05-31 | 李娜 | 一种治疗心律失常的药物组合物 |
| WO2018125810A1 (en) | 2016-12-28 | 2018-07-05 | Dart Neuroscience, Llc | Substituted pyrazolopyrimidinone compounds as pde2 inhibitors |
| EA038388B1 (ru) * | 2017-01-16 | 2021-08-19 | Кура Онколоджи, Инк. | Замещенные ингибиторы менина-mll и способы применения |
| JP7628392B2 (ja) | 2017-03-24 | 2025-02-10 | クラ オンコロジー，インク． | 血液悪性腫瘍およびユーイング肉腫を処置するための方法 |
| WO2018226976A1 (en) | 2017-06-08 | 2018-12-13 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with mll proteins |
| CN111032662B (zh) | 2017-06-21 | 2024-10-15 | 尚医治疗有限责任公司 | 与ras超家族相互作用的用于治疗癌症、炎性疾病、ras蛋白病和纤维化疾病的化合物 |
| US11098018B2 (en) * | 2017-08-14 | 2021-08-24 | Acesion Pharma Aps | Potassium channel inhibitors |
| US11649251B2 (en) | 2017-09-20 | 2023-05-16 | Kura Oncology, Inc. | Substituted inhibitors of menin-MLL and methods of use |
| US11434247B1 (en) | 2017-11-27 | 2022-09-06 | Dart Neuroscience Llc | Substituted furanopyrimidine compounds as PDE1 inhibitors |
| CN108117556A (zh) * | 2018-01-15 | 2018-06-05 | 王山川 | 一种细胞周期检查点激酶1抑制剂的合成方法 |
| JP7451419B2 (ja) | 2018-10-26 | 2024-03-18 | 大鵬薬品工業株式会社 | 新規なインダゾール化合物又はその塩 |
| US12391705B2 (en) | 2018-12-19 | 2025-08-19 | Shy Therapeutics, Llc | Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| JP7458406B2 (ja) | 2018-12-21 | 2024-03-29 | セルジーン コーポレーション | Ｒｉｐｋ２のチエノピリジン阻害剤 |
| GEP20247710B (en) | 2019-10-28 | 2024-12-25 | Merck Sharp & Dohme Llc | Small molecule inhibitors of kras g12c mutant |
| WO2021106231A1 (en) * | 2019-11-29 | 2021-06-03 | Taiho Pharmaceutical Co., Ltd. | A compound having inhibitory activity against kras g12d mutation |
| WO2022194191A1 (en) * | 2021-03-16 | 2022-09-22 | Guangdong Newopp Biopharmaceuticals Co., Ltd. | Heterocyclic compounds as inhibitors of kras g12d |
| JP2024511101A (ja) * | 2021-03-22 | 2024-03-12 | アセシオン ファーマ エイピーエス | 新規カリウムチャネル阻害剤 |
| TW202304925A (zh) * | 2021-03-26 | 2023-02-01 | 美商住友製藥腫瘤公司 | （呋喃并嘧啶—４—基）哌𠯤化合物及其用途 |
| CN115006468B (zh) * | 2022-06-28 | 2023-06-06 | 西安外事学院 | 一种复方中草药生发液及制备方法 |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4008726A1 (de) | 1990-03-19 | 1991-09-26 | Basf Ag | Thieno(2,3-d)pyrimidinderivate |
| AU651337B2 (en) * | 1990-03-30 | 1994-07-21 | Dowelanco | Thienopyrimidine derivatives |
| JP2001500482A (ja) | 1996-08-27 | 2001-01-16 | ノバルティス アクチェンゲゼルシャフト | 除草性ｓ置換１，２，４，６―チアトリアジン類 |
| WO2004011057A1 (en) | 1998-02-07 | 2004-02-05 | Advanced Cardiovascular Systems, Inc. | Perfusion dilatation catherer with expanded support coil |
| JP2001097979A (ja) | 1999-07-28 | 2001-04-10 | Takeda Chem Ind Ltd | 縮合複素環化合物、その製造法および用途 |
| CN1167697C (zh) | 1999-09-17 | 2004-09-22 | 日产化学工业株式会社 | 苯并吡喃衍生物 |
| US6887870B1 (en) | 1999-10-12 | 2005-05-03 | Bristol-Myers Squibb Company | Heterocyclic sodium/proton exchange inhibitors and method |
| SE9904738D0 (sv) | 1999-12-22 | 1999-12-22 | Astra Pharma Prod | Novel compounds |
| DE10031585A1 (de) * | 2000-06-29 | 2002-01-10 | Merck Patent Gmbh | 2-Aminoalkyl-thieno[2,3-d]pyrimidine |
| TW589305B (en) | 2001-02-14 | 2004-06-01 | Nissan Chemical Ind Ltd | 4-aminobenzopyran derivatives |
| CZ20033469A3 (cs) | 2001-06-25 | 2004-04-14 | Nissan Chemical Industries, Ltd. | Substituované benzopyranové deriváty proti arytmiím |
| AU2002336462A1 (en) | 2001-09-06 | 2003-03-24 | Millennium Pharmaceuticals, Inc. | Piperazine and homopiperazine compounds |
| JP2005508904A (ja) * | 2001-09-11 | 2005-04-07 | スミスクライン ビーチャム コーポレーション | 血管新生阻害剤としてのフロ−及びチエノピリミジン誘導体 |
| US20040138238A1 (en) | 2002-08-08 | 2004-07-15 | Dhanoa Dale S. | Substituted aminopyrimidine compounds as neurokinin antagonists |
| ES2217956B1 (es) * | 2003-01-23 | 2006-04-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de 4-aminotieno(2,3-d)pirimidin-6-carbonitrilo. |
| US20050222175A1 (en) | 2004-03-31 | 2005-10-06 | Dhanoa Dale S | New piperidinylamino-thieno[2,3-D] pyrimidine compounds |
| GB0315950D0 (en) * | 2003-06-11 | 2003-08-13 | Xention Discovery Ltd | Compounds |
| CA2528848C (en) * | 2003-06-11 | 2012-09-04 | Xention Discovery Limited | Thienopyrimidine derivatives as potassium channel inhibitors |
| US7594219B2 (en) | 2003-07-24 | 2009-09-22 | International Business Machines Corporation | Method and apparatus for monitoring compatibility of software combinations |
| TWI346112B (en) | 2004-02-25 | 2011-08-01 | Nissan Chemical Ind Ltd | Benzopyran compound |
| AU2005233437A1 (en) * | 2004-04-12 | 2005-10-27 | Sankyo Company, Limited | Thienopyridine derivatives |
| KR20070055486A (ko) | 2004-06-10 | 2007-05-30 | 젠션 디스커버리 리미티드 | 포타슘 채널 억제제로서 유효한 퓨라노피리미딘 화합물 |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| US8008487B2 (en) | 2004-10-21 | 2011-08-30 | Dow Agrosciences Llc | Substituted thieno[2,3-D]pyrimidines as fungicides |
| WO2006061642A1 (en) | 2004-12-09 | 2006-06-15 | Xention Discovery Limited | Compounds |
| US7576212B2 (en) * | 2004-12-09 | 2009-08-18 | Xention Limited | Thieno[2,3-B] pyridines as potassium channel inhibitors |
| US7576080B2 (en) | 2004-12-23 | 2009-08-18 | Memory Pharmaceuticals Corporation | Certain thienopyrimidine derivatives as phosphodiesterase 10 inhibitors |
| WO2006079916A1 (en) | 2005-01-26 | 2006-08-03 | Pharmacia & Upjohn Company Llc | Thieno [2,3-d] pyrimidine compounds as inhibitors of adp-mediated platelets aggregation |
| US20080176857A1 (en) | 2005-03-25 | 2008-07-24 | Michael Dalton Ennis | 4-Piperazinnylthieno[2,3-d]Pyrimidine Compounds as Platelet Aggregation Inhibitors |
| WO2006103555A1 (en) | 2005-03-28 | 2006-10-05 | Pharmacia & Upjohn Company Llc | 4-piperazinothieno [2, 3-d] pyrimidine compounds as platelet aggregation inhibitors |
| WO2006103544A2 (en) | 2005-03-28 | 2006-10-05 | Pharmacia & Upjohn Company Llc | 4-piperazinylthieno [2, 3-d] pyrimidine compounds as platelet aggregation inhibitors |
| EP1869051A1 (en) | 2005-03-28 | 2007-12-26 | Pharmacia & Upjohn Company LLC | 4-piperazinylthieno ý2,3-d¨pyrimidine compounds as platelet aggregation inhibitors |
| US20060281768A1 (en) * | 2005-06-10 | 2006-12-14 | Gaul Michael D | Thienopyrimidine and thienopyridine kinase modulators |
| WO2006136402A1 (en) * | 2005-06-22 | 2006-12-28 | Develogen Aktiengesellschaft | Thienopyrimidines for pharmaceutical compositions |
| ATE455117T1 (de) * | 2005-09-23 | 2010-01-15 | Equispharm Co Ltd | 5,6-dimethylthienoä2,3-diüpyrimidinderivate, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzung für die bekämpfung von viren |
| US20070213305A1 (en) * | 2005-11-02 | 2007-09-13 | Cytovia, Inc. | N-alkyl-N-aryl-thienopyrimidin-4-amines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| GB0525164D0 (en) * | 2005-12-09 | 2006-01-18 | Xention Discovery Ltd | Compounds |
| US8633201B2 (en) * | 2006-04-07 | 2014-01-21 | Boehringer Ingelheim International Gmbh | Thienopyrimidines having Mnk1/Mnk2 inhibiting activity for pharmaceutical compositions |
| CA2654842A1 (en) | 2006-06-12 | 2007-12-21 | Vertex Pharmaceuticals Incorporated | Thienopyrimidines useful as modulators of ion channels |
| DE102006030236A1 (de) | 2006-06-30 | 2008-01-03 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Direktoxidationsbrennstoffzelle für den konvektionsfreien Transport des Brennstoffs und Verfahren zum Betreiben der Brennstoffzelle |
| EP1947103A1 (en) | 2007-01-22 | 2008-07-23 | 4Sc Ag | Aryloxypropanolamines, methods of preparation thereof and use of aryloxypropanolamines as medicaments |
| GB0713602D0 (en) | 2007-07-12 | 2007-08-22 | Syngenta Participations Ag | Chemical compounds |
| BRPI0816922A2 (pt) * | 2007-09-14 | 2015-03-17 | Janssen Pharmaceutica Nv | Moduladores tieno e furo-pirimidina do receptor de histamina h4 |
| JP2011507910A (ja) | 2007-12-21 | 2011-03-10 | ユニバーシティー オブ ロチェスター | 真核生物の寿命を変更するための方法 |
| AR070449A1 (es) | 2008-02-22 | 2010-04-07 | Otsuka Pharma Co Ltd | Compuesto de benzodiazepina y composicion farmaceutica |
| US20100227853A1 (en) | 2008-04-18 | 2010-09-09 | Trustees Of Boston College | Inhibitors of cyclic amp phosphodiesterases |
| US7863291B2 (en) | 2008-04-23 | 2011-01-04 | Bristol-Myers Squibb Company | Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| UY32072A (es) * | 2008-08-26 | 2010-03-26 | Boehringer Ingelheim Int | Tienopirimidinas para composiciones farmacéuticas |
| TWI334124B (en) * | 2008-08-28 | 2010-12-01 | Au Optronics Corp | Display drive circuit for flat panel display and driving method for gate lines |
| TWI389913B (zh) | 2008-09-08 | 2013-03-21 | Lg Life Sciences Ltd | 并合雜環化合物 |
| AU2009291783A1 (en) | 2008-09-10 | 2010-03-18 | Alcon Research, Ltd | Aminopyrimidine inhibitors of histamine receptors for the treatment of disease |
| WO2010033127A1 (en) | 2008-09-22 | 2010-03-25 | Sionyx, Inc. | Response-enhanced monolithic-hybrid pixel |
| EP2473054B1 (en) | 2009-09-04 | 2017-06-14 | The Regents of the University of Michigan | Compositions and methods for treatment of leukemia |
| JP5619907B2 (ja) | 2009-10-29 | 2014-11-05 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | α７ニコチン性アセチルコリン受容体リガンドとしてのキヌクリジン化合物 |
| WO2011082268A2 (en) | 2009-12-30 | 2011-07-07 | Arqule Inc. | Substituted naphthalenyl-pyrimidine compounds |
| TW201219401A (en) * | 2010-09-14 | 2012-05-16 | Lexicon Pharmaceuticals Inc | Bicyclic inhibitors of Notum Pectinacetylesterase and methods of their use |
| DK2835131T3 (en) | 2010-12-14 | 2017-12-04 | Electrophoretics Ltd | Casein kinase 1 delta inhibitors (CK1 delta) |
| WO2012097013A1 (en) | 2011-01-10 | 2012-07-19 | Nimbus Iris, Inc. | Irak inhibitors and uses thereof |
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2012
- 2012-11-14 AR ARP120104296A patent/AR090037A1/es unknown
- 2012-11-15 EP EP12790948.9A patent/EP2780343A1/en not_active Withdrawn
- 2012-11-15 CN CN201280061286.3A patent/CN104011054B/zh not_active Expired - Fee Related
- 2012-11-15 WO PCT/GB2012/052842 patent/WO2013072694A1/en active Application Filing
- 2012-11-15 RU RU2014124101/04A patent/RU2014124101A/ru not_active Application Discontinuation
- 2012-11-15 TW TW101142693A patent/TWI498331B/zh not_active IP Right Cessation
- 2012-11-15 CA CA2855346A patent/CA2855346A1/en not_active Abandoned
- 2012-11-15 IN IN1183MUN2014 patent/IN2014MN01183A/en unknown
- 2012-11-15 JP JP2014540560A patent/JP2014533259A/ja active Pending
- 2012-11-15 US US14/358,722 patent/US9290511B2/en not_active Expired - Fee Related
- 2012-11-15 BR BR112014011671A patent/BR112014011671A2/pt not_active IP Right Cessation
- 2012-11-15 KR KR1020147015757A patent/KR20140094603A/ko not_active Withdrawn
- 2012-11-15 MX MX2014005935A patent/MX2014005935A/es not_active Application Discontinuation
- 2012-11-15 AU AU2012338570A patent/AU2012338570A1/en not_active Abandoned
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2014
- 2014-05-14 ZA ZA2014/03503A patent/ZA201403503B/en unknown
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2016
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| CN104011054A (zh) | 2014-08-27 |
| KR20140094603A (ko) | 2014-07-30 |
| AR090037A1 (es) | 2014-10-15 |
| US9290511B2 (en) | 2016-03-22 |
| CA2855346A1 (en) | 2013-05-23 |
| ZA201403503B (en) | 2016-09-28 |
| EP2780343A1 (en) | 2014-09-24 |
| BR112014011671A2 (pt) | 2017-05-30 |
| US20160152634A1 (en) | 2016-06-02 |
| NZ626199A (en) | 2015-04-24 |
| TWI498331B (zh) | 2015-09-01 |
| IN2014MN01183A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-07-03 |
| WO2013072694A1 (en) | 2013-05-23 |
| RU2014124101A (ru) | 2015-12-27 |
| AU2012338570A1 (en) | 2014-07-03 |
| US20140371203A1 (en) | 2014-12-18 |
| CN104011054B (zh) | 2016-08-24 |
| JP2014533259A (ja) | 2014-12-11 |
| TW201326178A (zh) | 2013-07-01 |
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