AU2003234628B2 - Substituted heterocyclic compounds and methods of use - Google Patents
Substituted heterocyclic compounds and methods of use Download PDFInfo
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- AU2003234628B2 AU2003234628B2 AU2003234628A AU2003234628A AU2003234628B2 AU 2003234628 B2 AU2003234628 B2 AU 2003234628B2 AU 2003234628 A AU2003234628 A AU 2003234628A AU 2003234628 A AU2003234628 A AU 2003234628A AU 2003234628 B2 AU2003234628 B2 AU 2003234628B2
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- pyridin
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US38269902P | 2002-05-21 | 2002-05-21 | |
| US60/382,699 | 2002-05-21 | ||
| PCT/US2003/015473 WO2003099808A1 (en) | 2002-05-21 | 2003-05-13 | Substituted heterocyclic compounds and methods of use |
Publications (2)
| Publication Number | Publication Date |
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| AU2003234628A1 AU2003234628A1 (en) | 2003-12-12 |
| AU2003234628B2 true AU2003234628B2 (en) | 2007-08-23 |
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| AU2003234628A Ceased AU2003234628B2 (en) | 2002-05-21 | 2003-05-13 | Substituted heterocyclic compounds and methods of use |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7026326B2 (https=) |
| EP (1) | EP1506186A1 (https=) |
| JP (2) | JP4606161B2 (https=) |
| AR (1) | AR039842A1 (https=) |
| AU (1) | AU2003234628B2 (https=) |
| CA (1) | CA2485166A1 (https=) |
| MX (1) | MXPA04011470A (https=) |
| PL (1) | PL376575A1 (https=) |
| TW (1) | TW200406399A (https=) |
| WO (1) | WO2003099808A1 (https=) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2007500128A (ja) * | 2003-07-25 | 2007-01-11 | アムジエン・インコーポレーテツド | 置換複素環式化合物及び使用方法 |
| AU2004267096B2 (en) | 2003-08-20 | 2008-10-02 | Amgen Inc. | Substituted pyrimdinone derivatives and methods of use |
| EP1838311A1 (en) * | 2004-12-24 | 2007-10-03 | Prosidion Limited | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| TWI417095B (zh) | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | １，４-二取代之３-氰基-吡啶酮衍生物及其作為ｍＧｌｕＲ２-受體之正向異位性調節劑之用途 |
| US7528448B2 (en) * | 2006-07-17 | 2009-05-05 | E.I. Du Pont De Nemours And Company | Thin film transistor comprising novel conductor and dielectric compositions |
| US8062824B2 (en) | 2006-07-17 | 2011-11-22 | E. I. Du Pont De Nemours And Company | Thermally imageable dielectric layers, thermal transfer donors and receivers |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| PL2203439T3 (pl) | 2007-09-14 | 2011-06-30 | Addex Pharmaceuticals Sa | 1',3'-dipodstawione-4-fenylo-3,4,5,6-tetrahydro-2H, 1'H-[1, 4']bipirydynylo-2'-ketony |
| US7666567B2 (en) | 2007-10-23 | 2010-02-23 | E. I. Du Pont De Nemours And Company | Negative imaging method for providing a patterned metal layer having high conductivity |
| US7666568B2 (en) * | 2007-10-23 | 2010-02-23 | E. I. Du Pont De Nemours And Company | Composition and method for providing a patterned metal layer having high conductivity |
| JP5547194B2 (ja) | 2008-09-02 | 2014-07-09 | ジャンセン ファーマシューティカルズ， インコーポレイテッド． | 代謝型グルタミン酸受容体の調節因子としての３−アザビシクロ［３．１．０］ヘキシル誘導体 |
| WO2010060589A1 (en) | 2008-11-28 | 2010-06-03 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
| MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| MY153912A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 1, 2, 4,-triazolo[4,3-a[pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
| CN102439008B (zh) | 2009-05-12 | 2015-04-29 | 杨森制药有限公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其用于治疗或预防神经和精神病症的用途 |
| PL2649069T3 (pl) | 2010-11-08 | 2016-01-29 | Janssen Pharmaceuticals Inc | Pochodne 1,2,4-triazolo[4,3-a]pirydyny i ich zastosowanie jako dodatnich allosterycznych modulatorów receptorów mGluR2 |
| CN103261195B (zh) | 2010-11-08 | 2015-09-02 | 杨森制药公司 | 1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途 |
| EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
| CN103635472B (zh) | 2011-02-28 | 2018-01-12 | 阵列生物制药公司 | 丝氨酸/苏氨酸激酶抑制剂 |
| JP6097289B2 (ja) | 2011-08-04 | 2017-03-15 | アレイ バイオファーマ、インコーポレイテッド | セリン／スレオニンキナーゼインヒビターとしてのキナゾリン化合物 |
| WO2013066729A1 (en) * | 2011-10-31 | 2013-05-10 | Merck Sharp & Dohme Corp. | Aminopyrimidinones as interleukin receptor-associated kinase inhibitors |
| US10531655B2 (en) | 2011-12-02 | 2020-01-14 | The Regents Of The University Of California | Reperfusion protection solution and uses thereof |
| HUE053994T2 (hu) | 2012-03-01 | 2021-08-30 | Array Biopharma Inc | Szerin/treonin kináz inhibitorok |
| AR092253A1 (es) | 2012-08-27 | 2015-04-08 | Array Biopharma Inc | Inhibidores de serina/treonina cinasa |
| JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
| JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
| KR20220049612A (ko) | 2014-01-21 | 2022-04-21 | 얀센 파마슈티카 엔.브이. | 대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도 |
| HUE053734T2 (hu) | 2014-01-21 | 2021-07-28 | Janssen Pharmaceutica Nv | 2-es altípusú metabotróp glutamáterg receptor pozitív allosztérikus modulátorait tartalmazó kombinációk és alkalmazásuk |
| AU2018251415B2 (en) * | 2017-04-11 | 2021-08-05 | Mitsui Chemicals Crop & Life Solutions, Inc. | Pyridone compounds and agricultural and horticultural fungicides containing the same as active ingredients |
| CN111094271B (zh) * | 2017-08-23 | 2023-02-28 | 思普瑞特生物科学公司 | 吡啶胺-吡啶酮化合物和嘧啶胺-吡啶酮化合物 |
| WO2019038387A1 (en) * | 2017-08-23 | 2019-02-28 | Sprint Bioscience Ab | PYRIDYLPYRIDONE COMPOUNDS |
| US12479816B2 (en) | 2019-02-08 | 2025-11-25 | University of Pittsburgh—of the Commonwealth System of Higher Education | 20-HETE formation inhibitors |
| CA3199988A1 (en) | 2020-11-25 | 2022-06-02 | Daniel L. Flynn | Pyridylpyridone derivatives as vsp34 inhibitors for use in the treatment of a viral infection |
| KR20240149429A (ko) * | 2022-02-16 | 2024-10-14 | 듀크 스트리트 바이오 리미티드 | 약학적 화합물 |
| US11993580B1 (en) | 2022-12-02 | 2024-05-28 | Neumora Therapeutics, Inc. | Methods of treating neurological disorders |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998024780A2 (en) * | 1996-12-05 | 1998-06-11 | Amgen Inc. | Substituted pyrimidinone and pyridinone compounds and their use |
| WO1998024782A2 (en) * | 1996-12-05 | 1998-06-11 | Amgen Inc. | Substituted pyrimidine compounds and their use |
| US6096753A (en) * | 1996-12-05 | 2000-08-01 | Amgen Inc. | Substituted pyrimidinone and pyridone compounds and methods of use |
| US6410729B1 (en) * | 1996-12-05 | 2002-06-25 | Amgen Inc. | Substituted pyrimidine compounds and methods of use |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2602794A (en) * | 1952-07-08 | Process for preparation of x-amino-s | ||
| WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
| JPH11501506A (ja) | 1994-12-12 | 1999-02-09 | ベス イスラエル デアコネス メディカル センター | キメラ型サイトカインおよびその利用 |
| CA2244664C (en) | 1996-02-09 | 2008-06-03 | Amgen Inc. | Composition comprising interleukin-1 inhibitor and controlled release polymer |
| US6100071A (en) | 1996-05-07 | 2000-08-08 | Genentech, Inc. | Receptors as novel inhibitors of vascular endothelial growth factor activity and processes for their production |
| JP4771563B2 (ja) | 1996-12-06 | 2011-09-14 | アムジエン・インコーポレーテツド | Ｉｌ−１媒介疾患を処置するためにｉｌ−１インヒビターを使用する組合せ療法 |
| KR19980066046A (ko) | 1997-01-18 | 1998-10-15 | 정용훈 | 고역가의 CTLA4-Ig 융합단백질 |
| CN1202862C (zh) | 1997-04-17 | 2005-05-25 | 安姆根有限公司 | 包含具有抗体Fc链的稳定、有活性人OB蛋白的结合物的组合物及方法 |
| WO2002074753A2 (de) * | 2001-03-15 | 2002-09-26 | Basf Aktiengesellschaft | 5-phenylpyrimidine, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekaempfung von schadpilzen |
-
2003
- 2003-05-13 CA CA002485166A patent/CA2485166A1/en not_active Abandoned
- 2003-05-13 JP JP2004507465A patent/JP4606161B2/ja not_active Expired - Fee Related
- 2003-05-13 WO PCT/US2003/015473 patent/WO2003099808A1/en not_active Ceased
- 2003-05-13 MX MXPA04011470A patent/MXPA04011470A/es active IP Right Grant
- 2003-05-13 AU AU2003234628A patent/AU2003234628B2/en not_active Ceased
- 2003-05-13 US US10/438,553 patent/US7026326B2/en not_active Expired - Lifetime
- 2003-05-15 EP EP03728971A patent/EP1506186A1/en not_active Withdrawn
- 2003-05-15 PL PL376575A patent/PL376575A1/pl not_active Application Discontinuation
- 2003-05-21 TW TW092113725A patent/TW200406399A/zh unknown
- 2003-05-22 AR ARP030101777A patent/AR039842A1/es not_active Application Discontinuation
-
2010
- 2010-07-09 JP JP2010157000A patent/JP2010280669A/ja not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998024780A2 (en) * | 1996-12-05 | 1998-06-11 | Amgen Inc. | Substituted pyrimidinone and pyridinone compounds and their use |
| WO1998024782A2 (en) * | 1996-12-05 | 1998-06-11 | Amgen Inc. | Substituted pyrimidine compounds and their use |
| US6096753A (en) * | 1996-12-05 | 2000-08-01 | Amgen Inc. | Substituted pyrimidinone and pyridone compounds and methods of use |
| US6410729B1 (en) * | 1996-12-05 | 2002-06-25 | Amgen Inc. | Substituted pyrimidine compounds and methods of use |
Non-Patent Citations (2)
| Title |
|---|
| Tanaka, A. et al. Chem. Pharm. Bull. 1994, 42(9), 1828-1834. * |
| Tanaka, A. et al. Chem. Pharm. Bull. 1994, 42(9), 1835-1840 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003234628A1 (en) | 2003-12-12 |
| TW200406399A (en) | 2004-05-01 |
| US7026326B2 (en) | 2006-04-11 |
| PL376575A1 (pl) | 2006-01-09 |
| WO2003099808A8 (en) | 2009-02-05 |
| JP2010280669A (ja) | 2010-12-16 |
| US20050038010A1 (en) | 2005-02-17 |
| CA2485166A1 (en) | 2003-12-04 |
| EP1506186A1 (en) | 2005-02-16 |
| WO2003099808A1 (en) | 2003-12-04 |
| AR039842A1 (es) | 2005-03-02 |
| JP2005530810A (ja) | 2005-10-13 |
| JP4606161B2 (ja) | 2011-01-05 |
| MXPA04011470A (es) | 2005-02-14 |
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