TWI419692B - 細胞激素抑制劑 - Google Patents
細胞激素抑制劑 Download PDFInfo
- Publication number
- TWI419692B TWI419692B TW097125251A TW97125251A TWI419692B TW I419692 B TWI419692 B TW I419692B TW 097125251 A TW097125251 A TW 097125251A TW 97125251 A TW97125251 A TW 97125251A TW I419692 B TWI419692 B TW I419692B
- Authority
- TW
- Taiwan
- Prior art keywords
- phenyl
- imidazo
- oxadiazol
- pyridazine
- alkyl
- Prior art date
Links
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/934,154 US7868001B2 (en) | 2007-11-02 | 2007-11-02 | Cytokine inhibitors |
Publications (2)
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| TW201002327A TW201002327A (en) | 2010-01-16 |
| TWI419692B true TWI419692B (zh) | 2013-12-21 |
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| Country | Link |
|---|---|
| US (1) | US7868001B2 (enExample) |
| EP (1) | EP2214669B1 (enExample) |
| JP (1) | JP5733982B2 (enExample) |
| KR (1) | KR20100101581A (enExample) |
| AU (1) | AU2008318491B2 (enExample) |
| CA (1) | CA2704431A1 (enExample) |
| MX (1) | MX2010004774A (enExample) |
| MY (1) | MY153065A (enExample) |
| RU (1) | RU2485113C2 (enExample) |
| TW (1) | TWI419692B (enExample) |
| WO (1) | WO2009059162A1 (enExample) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH066861Y2 (ja) | 1991-02-19 | 1994-02-23 | 太陽電子株式会社 | パチンコ式組合せゲーム機 |
| PL2485731T4 (pl) * | 2009-10-06 | 2017-07-31 | Millennium Pharmaceuticals, Inc. | Związki heterocykliczne użyteczne jako inhibitory PDK1 |
| WO2011137587A1 (en) * | 2010-05-06 | 2011-11-10 | Hutchison Medipharma Limited | Cytokine inhibitors |
| FR2962649B1 (fr) | 2010-07-19 | 2025-10-24 | Conservatoire Nat Arts Et Metiers | Traitement d'une pathologie liee a un effet excessif du tnf par un compose de benzene sulfonamide |
| RS57508B1 (sr) | 2013-09-06 | 2018-10-31 | Aurigene Discovery Tech Ltd | 1,2,4-derivati oksadiazola kao imunomodulatori |
| EA201650031A1 (ru) | 2014-05-15 | 2017-06-30 | Итеос Терапьютик | Производные пирролидин-2,5-диона, фармацевтические композиции и способы применения в качестве ингибиторов ido1 |
| KR102302109B1 (ko) * | 2014-07-24 | 2021-09-14 | 삼성디스플레이 주식회사 | 유기 화합물 및 이를 포함하는 유기 발광 장치 |
| KR102894264B1 (ko) | 2015-03-10 | 2025-12-02 | 오리진 온콜로지 리미티드 | 면역조절제로서의 1,2,4-옥사다이아졸 및 티아다이아졸 화합물 |
| BR112017019699A2 (pt) | 2015-03-17 | 2018-09-04 | Pfizer Inc. | derivados substituídos por 3-indol, composições farmacêuticas e métodos para uso |
| US10544095B2 (en) | 2015-08-10 | 2020-01-28 | Pfizer Inc. | 3-indol substituted derivatives, pharmaceutical compositions and methods for use |
| US20170107216A1 (en) | 2015-10-19 | 2017-04-20 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| MD3377488T2 (ro) | 2015-11-19 | 2023-02-28 | Incyte Corp | Compuși heterociclici ca imunomodulatori |
| ES2916874T3 (es) | 2015-12-17 | 2022-07-06 | Incyte Corp | Derivados de N-fenil-piridina-2-carboxamida y su uso como moduladores de la interacción proteína/proteína PD-1/PD-L1 |
| CA3009474A1 (en) | 2015-12-22 | 2017-06-29 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| ES2906460T3 (es) | 2016-05-06 | 2022-04-18 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| EP3464279B1 (en) | 2016-05-26 | 2021-11-24 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| SG11201811414TA (en) | 2016-06-20 | 2019-01-30 | Incyte Corp | Heterocyclic compounds as immunomodulators |
| MA45669A (fr) | 2016-07-14 | 2019-05-22 | Incyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
| US20180057486A1 (en) | 2016-08-29 | 2018-03-01 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| WO2018118781A1 (en) * | 2016-12-20 | 2018-06-28 | Fmc Corporation | Fungicidal oxadiazoles |
| WO2018119286A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Bicyclic heteroaromatic compounds as immunomodulators |
| WO2018119221A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Pyridine derivatives as immunomodulators |
| EP4223369A1 (en) | 2016-12-22 | 2023-08-09 | Incyte Corporation | Immunomodulator compounds and methods of use |
| US10308644B2 (en) | 2016-12-22 | 2019-06-04 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| WO2018119236A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Triazolo[1,5-a]pyridine derivatives as immunomodulators |
| WO2019061324A1 (en) | 2017-09-29 | 2019-04-04 | Curis Inc. | CRYSTALLINE FORMS OF IMMUNOMODULATORS |
| AU2018348350B2 (en) | 2017-10-11 | 2024-05-02 | Aurigene Oncology Limited | Crystalline forms of 3-substituted 1,2,4-oxadiazole |
| MX2020004531A (es) | 2017-11-03 | 2020-08-03 | Aurigene Discovery Tech Ltd | Inhibidores dobles de tim-3 y las vias de pd-1. |
| EP3706798A1 (en) | 2017-11-06 | 2020-09-16 | Aurigene Discovery Technologies Limited | Conjoint therapies for immunomodulation |
| SMT202300065T1 (it) | 2018-03-30 | 2023-05-12 | Incyte Corp | Composti eterociclici come immunomodulatori |
| CN112752756B (zh) | 2018-05-11 | 2024-06-25 | 因赛特公司 | 作为PD-L1免疫调节剂的四氢-咪唑并[4,5-c]吡啶衍生物 |
| TW202115059A (zh) | 2019-08-09 | 2021-04-16 | 美商英塞特公司 | Ｐｄ—１／ｐｄ—ｌ１抑制劑之鹽 |
| US20220267270A1 (en) * | 2019-08-30 | 2022-08-25 | University Of South Florida | Sting modulators, compositions, and methods of use |
| JP7559059B2 (ja) | 2019-09-30 | 2024-10-01 | インサイト・コーポレイション | 免疫調節剤としてのピリド［３，２－ｄ］ピリミジン化合物 |
| EP4058461A1 (en) | 2019-11-11 | 2022-09-21 | Incyte Corporation | Salts and crystalline forms of a pd-1/pd-l1 inhibitor |
| IL297963A (en) | 2020-05-07 | 2023-01-01 | Adorx Therapeutics Ltd | Antagonists of the adenosine a2a receptor |
| IL302590A (en) | 2020-11-06 | 2023-07-01 | Incyte Corp | Process for preparing PD-1/PD-L1 inhibitor and salts and crystalline forms thereof |
| US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
| US11760756B2 (en) | 2020-11-06 | 2023-09-19 | Incyte Corporation | Crystalline form of a PD-1/PD-L1 inhibitor |
| GB202019622D0 (en) * | 2020-12-11 | 2021-01-27 | Adorx Therapeutics Ltd | Antagonist compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007034278A2 (en) * | 2005-09-19 | 2007-03-29 | Pfizer Products Inc. | Fused imidazole derivatives as c3a receptor antagonists |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5745237B2 (enExample) * | 1974-03-27 | 1982-09-27 | ||
| GB1442707A (en) * | 1973-07-07 | 1976-07-14 | Yoshitomi Pharmaceutical | Substituted phenylalkanoic acids and their derivatives and pharma ceutical compositions thereof |
| DE3446812A1 (de) | 1984-12-21 | 1986-06-26 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue imidazoderivate, ihre herstellung und diese verbindungen enthaltende arzneimittel |
| DE3446778A1 (de) | 1984-12-21 | 1986-07-03 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue imidazoderivate, ihre herstellung und diese verbindungen enthaltende arzneimittel |
| IL86462A (en) * | 1987-05-29 | 1992-12-01 | Fujisawa Pharmaceutical Co | Alkanesulfonanilide derivatives, processes for preparation thereof and pharmaceutical compositions comprising the same |
| WO1989001478A1 (en) * | 1987-08-07 | 1989-02-23 | The Australian National University | ARYLOXY- AND ARALKYLTHIO-IMIDAZO[1,2-b]PYRIDAZINES |
| DE4405378A1 (de) * | 1994-02-19 | 1995-08-24 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| JPH07291976A (ja) * | 1994-04-27 | 1995-11-07 | Otsuka Pharmaceut Factory Inc | イミダゾ〔２，１−ｂ〕チアゾール誘導体 |
| JP3477238B2 (ja) * | 1994-04-27 | 2003-12-10 | 株式会社大塚製薬工場 | イミダゾ〔１，２−ａ〕ピリジン誘導体 |
| UA73492C2 (en) * | 1999-01-19 | 2005-08-15 | Aromatic heterocyclic compounds as antiinflammatory agents | |
| DE60010448T2 (de) * | 1999-03-17 | 2005-04-07 | Astrazeneca Ab | Amid-derivate |
| US6403567B1 (en) | 1999-06-22 | 2002-06-11 | Cv Therapeutics, Inc. | N-pyrazole A2A adenosine receptor agonists |
| CA2397661C (en) * | 2000-03-01 | 2012-01-03 | Janssen Pharmaceutica N.V. | 2,4-disubstituted thiazolyl derivatives |
| WO2002049632A1 (en) * | 2000-12-18 | 2002-06-27 | Institute Of Medicinal Molecular Design. Inc. | Inhibitors against the production and release of inflammatory cytokines |
| US6596731B2 (en) * | 2001-03-27 | 2003-07-22 | Hoffmann-La Roche Inc. | Substituted imidazo[1,2-A] pyridine derivatives |
| CA2450555A1 (en) * | 2001-06-25 | 2003-01-03 | Merck & Co., Inc. | (pyrimidyl)(phenyl)substituted fused heteroaryl p38 inhibiting and pkg kinase inhibiting compounds |
| EP1426050A4 (en) * | 2001-08-23 | 2005-05-25 | Takeda Pharmaceutical | JNK INHIBITORS |
| ATE511858T1 (de) * | 2002-02-05 | 2011-06-15 | Astellas Pharma Inc | 2,4,6-triamino-1,3,5-triazin-derivat |
| US7105533B2 (en) * | 2002-09-13 | 2006-09-12 | Merck & Co., Inc. | Fused heterobicyclo substituted phenyl metabotropic glutamate-5 modulators |
| JP2006516250A (ja) | 2002-12-18 | 2006-06-29 | サイトビア インコーポレイティッド | カスパーゼ活性化剤およびアポトーシス誘導物質としての３，５−二置換−［１，２，４］−オキサジアゾールおよびそれらの誘導体ならびにそれらの使用 |
| RU2006100301A (ru) | 2003-06-11 | 2006-07-10 | Санкио Компани Лимитед (JP) | Соединение циклического третичного амина |
| CA2551867C (en) | 2003-12-31 | 2010-08-17 | Schering-Plough Ltd. | Control of parasites in animals by the use of imidazo[1,2-b]pyridazine derivatives |
| JP2008504294A (ja) * | 2004-06-25 | 2008-02-14 | アムジエン・インコーポレーテツド | サイトカイン介在疾患および他の疾患の治療において有用な縮合トリアゾールおよびインダゾール |
| US20060064650A1 (en) * | 2004-09-20 | 2006-03-23 | International Business Machines Corporation | Method, system, and computer program product for type-based table navigation |
| KR20070057965A (ko) * | 2004-09-21 | 2007-06-07 | 신타 파마슈티칼스 코프. | 염증 및 면역 관련 용도를 위한 화합물 |
| EP1812439B2 (en) | 2004-10-15 | 2017-12-06 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| JPWO2006070943A1 (ja) * | 2004-12-28 | 2008-06-12 | 武田薬品工業株式会社 | 縮合イミダゾール化合物およびその用途 |
| US20090163476A1 (en) * | 2005-03-03 | 2009-06-25 | Sirtris Pharmaceuticals, Inc. | N-Phenyl Benzamide Derivatives as Sirtuin Modulators |
| US7345178B2 (en) * | 2005-08-04 | 2008-03-18 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| DE102005042742A1 (de) * | 2005-09-02 | 2007-03-08 | Schering Ag | Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| AU2006311786A1 (en) * | 2005-11-04 | 2007-05-18 | Merck Sharp & Dohme Corp. | Diphenylmethane derivatives as inhibitors of leukotriene biosynthesis |
| DE102006011574A1 (de) * | 2006-03-10 | 2007-10-31 | Grünenthal GmbH | Substituierte Imidazo[2,1-b]thiazol-Verbindungen und ihre Verwendung zur Herstellung von Arzneimitteln |
| EP1845098A1 (en) * | 2006-03-29 | 2007-10-17 | Ferrer Internacional, S.A. | Imidazo[1,2-b]pyridazines, their processes of preparation and their use as GABA receptor ligands |
| WO2007123892A2 (en) * | 2006-04-17 | 2007-11-01 | Arqule Inc. | Raf inhibitors and their uses |
| US20080015193A1 (en) | 2006-06-20 | 2008-01-17 | Mendoza Jose S | Certain azoles exhibiting ATP-utilizing enzyme inhibitory activity, compositions, and uses thereof |
| EP1964841A1 (en) | 2007-02-28 | 2008-09-03 | sanofi-aventis | Imidazo[1,2-a]azine and their use as pharmaceuticals |
| CA2707360A1 (en) * | 2007-06-20 | 2008-12-24 | Merck Sharp & Dohme Corp. | Diphenyl substituted alkanes |
| FR2918061B1 (fr) * | 2007-06-28 | 2010-10-22 | Sanofi Aventis | Derives de 6-cycloamino-3-(pyridin-4-yl)imidazo°1,2-b!- pyridazine,leur preparation et leur application en therapeutique. |
| FR2918986B1 (fr) * | 2007-07-19 | 2009-09-04 | Sanofi Aventis Sa | Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique |
| CA2695251C (en) * | 2007-08-14 | 2016-06-21 | Bayer Schering Pharma Aktiengesellschaft | Fused imidazoles for cancer treatment |
| EP2083009A1 (de) * | 2008-01-22 | 2009-07-29 | Grünenthal GmbH | Substituierte Tethrahydroimidazopyridin-Verbindungen und deren Verwendung in Arzneimitteln |
| CA2722418C (en) | 2008-05-13 | 2013-09-17 | Irm Llc | Fused nitrogen containing heterocycles and compositions thereof as kinase inhibitors |
| PA8854101A1 (es) * | 2008-12-18 | 2010-07-27 | Ortho Mcneil Janssen Pharm | Derivados de imidazol bicíclicos sustituidos como moduladores de gamma secretasa |
-
2007
- 2007-11-02 US US11/934,154 patent/US7868001B2/en not_active Expired - Fee Related
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2008
- 2008-07-04 TW TW097125251A patent/TWI419692B/zh not_active IP Right Cessation
- 2008-10-31 AU AU2008318491A patent/AU2008318491B2/en not_active Ceased
- 2008-10-31 WO PCT/US2008/082027 patent/WO2009059162A1/en not_active Ceased
- 2008-10-31 MY MYPI20101943 patent/MY153065A/en unknown
- 2008-10-31 KR KR1020107011579A patent/KR20100101581A/ko not_active Abandoned
- 2008-10-31 RU RU2010122333/04A patent/RU2485113C2/ru not_active IP Right Cessation
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- 2008-10-31 EP EP08843535.9A patent/EP2214669B1/en not_active Not-in-force
- 2008-10-31 JP JP2010532289A patent/JP5733982B2/ja not_active Expired - Fee Related
- 2008-10-31 CA CA2704431A patent/CA2704431A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007034278A2 (en) * | 2005-09-19 | 2007-03-29 | Pfizer Products Inc. | Fused imidazole derivatives as c3a receptor antagonists |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100101581A (ko) | 2010-09-17 |
| EP2214669B1 (en) | 2015-04-01 |
| RU2485113C2 (ru) | 2013-06-20 |
| WO2009059162A1 (en) | 2009-05-07 |
| CA2704431A1 (en) | 2009-05-07 |
| MX2010004774A (es) | 2010-07-02 |
| EP2214669A1 (en) | 2010-08-11 |
| RU2010122333A (ru) | 2011-12-10 |
| JP2011502996A (ja) | 2011-01-27 |
| MY153065A (en) | 2014-12-31 |
| US20090118292A1 (en) | 2009-05-07 |
| AU2008318491A1 (en) | 2009-05-07 |
| JP5733982B2 (ja) | 2015-06-10 |
| US7868001B2 (en) | 2011-01-11 |
| EP2214669A4 (en) | 2011-11-09 |
| AU2008318491B2 (en) | 2013-09-19 |
| TW201002327A (en) | 2010-01-16 |
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