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1. 发明申请

WO2006094187A3 PHTHALAZINE, AZA- AND DIAZA-PHTHALAZINE COMPOUNDS AND METHODS OF USE 审中-公开
公开(公告)号：WO2006094187A3
公开(公告)日：2006-09-08
申请号：PCT/US2006/007583
申请日：2006-03-03
申请人： AMGEN INC
发明人： TASKER, Andrew , ZHANG, Dawei , CAO, Guo-Qiang , CHAKRABARTI, Partha, Pratim , FALSEY, James, Richard , HERBERICH, Bradley, J. , HUNGATE, Randall, W. , PETTUS, Liping, H. , REED, Anthony , RZASA, Robert, M. , SHAM, Kelvin, K.C. , THAMAN, Maya, C. , XU, Shimin
IPC分类号： C07D237/32 , C07D237/34 , C07D237/30 , C07D413/12 , C07D417/12 , C07D498/04 , C07D487/04 , C07D417/04 , C07D491/10 , C07D409/04 , C07D401/04 , C07D403/04 , A61K31/502 , A61P29/00
摘要： The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula (I), wherein A 1 , A 2 , B, R 1 , R 2 , R 3 and R 4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I. The compounds have effect on the levels of TNF-X and various Interleukins.

2. 发明申请

WO2008076427A3 NAPHTHALENONE COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, COMPOSITIONS, AND USES THEREOF 审中-公开
公开(公告)号：WO2008076427A3
公开(公告)日：2008-06-26
申请号：PCT/US2007/025819
申请日：2007-12-17
申请人： AMGEN INC. , ALLEN, Jennifer, R. , BISWAS, Kaustav , BRYAN, Marian, C. , BURLI, Roland , CAO, Guo-Qiang , FROHN, Michael, J. , GOLDEN, Jennifer, E. , MERCEDE, Stephanie , NEIRA, Susana , PETERKIN, Tanya , PICKRELL, Alexander, J. , REED, Anthony , TEGLEY, Christopher, M. , WANG, Xiang
发明人： ALLEN, Jennifer, R. , BISWAS, Kaustav , BRYAN, Marian, C. , BURLI, Roland , CAO, Guo-Qiang , FROHN, Michael, J. , GOLDEN, Jennifer, E. , MERCEDE, Stephanie , NEIRA, Susana , PETERKIN, Tanya , PICKRELL, Alexander, J. , REED, Anthony , TEGLEY, Christopher, M. , WANG, Xiang
IPC分类号： C07D311/96 , C07C235/82 , C07D213/56 , C07D213/61 , C07D307/94 , C07C237/24 , C07D221/20 , C07D215/48 , C07C59/88 , C07D217/02 , A61K31/352 , A61P9/10
摘要： Compounds of Formula (I) and Formula (II) are useful as inhibitors of HIF prolyl hydroxylases. Compounds of Formula(I) and Formula (II) have the following structures, where the definitions of the variables are provided herein.

3. 发明申请

WO2008130600A3 QUINOLONES AND AZAQUINOLONES THAT INHIBIT PROLYL HYDROXYLASE 审中-公开
公开(公告)号：WO2008130600A3
公开(公告)日：2008-10-30
申请号：PCT/US2008/004965
申请日：2008-04-16
申请人： AMGEN INC. , ALLEN, Jennifer, R. , BURLI, Roland , BRYAN, Marian, C. , CAO, Guo-Qiang , NEIRA, Susana, C. , REED, Anthony, B.
发明人： ALLEN, Jennifer, R. , BURLI, Roland , BRYAN, Marian, C. , CAO, Guo-Qiang , NEIRA, Susana, C. , REED, Anthony, B.
IPC分类号： C07D215/22 , C07D405/04 , C07D409/04 , C07D471/04 , A61K31/435 , A61K31/4375 , A61P7/06
摘要： Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

4. 发明申请

WO2003099808A8 SUBSTITUTED HETEROCYCLIC COMPOUNDS AND METHODS OF USE 审中-公开
公开(公告)号：WO2003099808A8
公开(公告)日：2003-12-04
申请号：PCT/US2003/015473
申请日：2003-05-13
申请人： AMGEN INC. , DOMINGUEZ, Celia , ZHANG, Dawei , CAO, Guo-Qiang , GOLDBERG, Martin, H. , HONG, Fang-Tsao , SHAM, Kelvin, K., C. , TADESSE, Seifu , TAMAYO, Nuria, A. , WEILER, Kurt, E. , LIAO, Hongyu
发明人： DOMINGUEZ, Celia , ZHANG, Dawei , CAO, Guo-Qiang , GOLDBERG, Martin, H. , HONG, Fang-Tsao , SHAM, Kelvin, K., C. , TADESSE, Seifu , TAMAYO, Nuria, A. , WEILER, Kurt, E. , LIAO, Hongyu
IPC分类号： C07D401/04
摘要： The present invention relates to compounds having the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R l is a saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, O and S, wherein the ring may be fused with a benzo group, and is substituted by 0, 1 or 2 oxo groups, and wherein R 1 is additionally substituted; and R 2 is a substituted C 1 -6 balkyl. Also included is a method of prophylaxis or treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

5. 发明申请

WO2003099808A1 SUBSTITUTED HETEROCYCLIC COMPOUNDS AND METHODS OF USE 审中-公开
标题翻译：取代的杂环化合物及其使用方法
公开(公告)号：WO2003099808A1
公开(公告)日：2003-12-04
申请号：PCT/US2003/015473
申请日：2003-05-15
申请人： AMGEN INC. , DOMINGUEZ, Celia , ZHANG, Dawei , CAO, Guo-Qiang , GOLDBERG, Martin, H. , HONG, Fang-Tsao , SHAM, Kelvin, K., C. , TADESSE, Seifu , TAMAYO, Nuria, A. , WEILER, Kurt, E. , LIAO, Hongyu
发明人： DOMINGUEZ, Celia , ZHANG, Dawei , CAO, Guo-Qiang , GOLDBERG, Martin, H. , HONG, Fang-Tsao , SHAM, Kelvin, K., C. , TADESSE, Seifu , TAMAYO, Nuria, A. , WEILER, Kurt, E. , LIAO, Hongyu
IPC分类号： C07D401/04
CPC分类号： C07D401/04
摘要： The present invention relates to compounds having the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R l is a saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, O and S, wherein the ring may be fused with a benzo group, and is substituted by 0, 1 or 2 oxo groups, and wherein R 1 is additionally substituted; and R 2 is a substituted C 1 -6 balkyl. Also included is a method of prophylaxis or treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.
摘要翻译：本发明涉及具有通式（I）的化合物或其药学上可接受的盐，其中R 1是含有0,1,2或3个原子的饱和或不饱和的5-，6-或7-元环选自N，O和S，其中所述环可以与苯并稠合，并且被0,1或2个氧代基取代，并且其中R 1另外被取代; R 2是取代的C 1-6烷基。还包括预防或治疗炎症，类风湿性关节炎，斑节病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸窘迫综合征（ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉退化，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应，阿尔茨海默病，中风，心肌梗死，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV1，HIV-2，HIV-3，巨细胞病毒），流感，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的化合物如上所述。

6. 发明公开

EP1727821A1 SUBSTITUTED DIAZABICYCLOHEPTANES AND THEIR USE AS PROTEIN KINASE INHIBITORS 审中-公开
标题翻译：取代DIAZABICYCLOHEPTANE及其作为激酶抑制剂的蛋白质
公开(公告)号：EP1727821A1
公开(公告)日：2006-12-06
申请号：EP05705583.2
申请日：2005-01-12
申请人： Amgen Inc.
发明人： CAO, Guo-Qiang , CHEN, Jian, J. , DOMINGUEZ, Celia , REED, Anthony , SHAM, Kelvin, K., C. , THAMAN, Maya, C. , ZHANG, Dawei , HERBERICH, Bradley, J.
IPC分类号： C07D487/08 , A61K31/4995 , A61P19/02
CPC分类号： C07D487/06 , C07D213/56 , C07D239/95 , C07D401/04 , C07D401/14 , C07D417/14
摘要： The present invention relates to therapeutic diazobicyclo pyridines and their use in the treatment of arthritis, rheumatoid arthritis, psoriatic arthritis or osteoarthritis, organ transplant, acute transplant or heterograft and homograft rejection, ischemic and reperfusion injury, transplantation tolerance induction, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lupus, graft vs. host diseases, T -cell mediated hypersensitivity diseases, contact hypersensitivity, delayed-type hypersensitivity, gluten-sensitive enteropathy, Type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism,Graves' Disease, Addison's disease, autoimmune polyglandular disease, autoimmune alopecia, pernicious anemia, vitiligo, autoimmune hypopituatarism, Guillain-Barre syndrome, autoimmune diseases, glomerulonephritis, serum sickness, uticaria, respiratory allergies, asthma, hayfever, allergic rhinitis, skin allergies, scleracielma, mycosis fungoides, acute inflammatory responses, acute respiratory distress syndrome, dermatomyositis, alopecia areata, chronic actinic dermatitis, eczema, Behcet's disease, Pustulosis palmoplanteris, Pyoderma gangrenum, Sezary's syndrome, atopic dermatitis, systemic schlerosis, morphea, Type II diabetes and cancers where PKC theta or other PKC-family kinases are activated, overexpressed or facilitate tumor growth or survival of tumor cells, T cell leukemia, thymoma, T and B cell lymphoma, colon carcinoma, breast carcinoma and lung carcinoma or provides resistance to chemotherapeutic drugs.

7. 发明申请

WO2008076425A1 AZAQUINOLONE BASED COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, COMPOSITIONS, AND USES THEREOF 审中-公开
标题翻译：基于AZAQUINOLONE的化合物展示丙烯酸羟化酶抑制活性，组合物及其用途
公开(公告)号：WO2008076425A1
公开(公告)日：2008-06-26
申请号：PCT/US2007/025799
申请日：2007-12-17
申请人： AMGEN INC. , ALLEN, Jennifer, R. , BISWAS, Kaustav , CAO, Guo-Qiang , GOLDEN, Jennifer, E. , MERCEDE, Stephanie , PETERKIN, Tanya , REED, Anthony , TEGLEY, Christopher, M.
发明人： ALLEN, Jennifer, R. , BISWAS, Kaustav , CAO, Guo-Qiang , GOLDEN, Jennifer, E. , MERCEDE, Stephanie , PETERKIN, Tanya , REED, Anthony , TEGLEY, Christopher, M.
IPC分类号： C07D487/04
CPC分类号： C07D471/04
摘要： Compounds of Formula (I) are useful as inhibitors of HIF prolyl hydroxylases where the definitions of the variables are provided herein.
摘要翻译：式（I）的化合物可用作HIF脯氨酰羟化酶的抑制剂，其中本文提供变量的定义。

8. 发明申请

WO2005070934A1 SUBSTITUTED DIAZABICYCLOHEPTANES AND THEIR USE AS PROTEIN KINASE INHIBITORS 审中-公开
标题翻译：替代双联蛋白及其作为蛋白激酶抑制剂的用途
公开(公告)号：WO2005070934A1
公开(公告)日：2005-08-04
申请号：PCT/US2005/000993
申请日：2005-01-12
申请人： AMGEN INC. , CAO, Guo-Qiang , CHEN, Jian, J. , DOMINGUEZ, Celia , REED, Anthony , SHAM, Kelvin, K., C. , THAMAN, Maya, C. , ZHANG, Dawei , HERBERICH, Bradley, J.
发明人： CAO, Guo-Qiang , CHEN, Jian, J. , DOMINGUEZ, Celia , REED, Anthony , SHAM, Kelvin, K., C. , THAMAN, Maya, C. , ZHANG, Dawei , HERBERICH, Bradley, J.
IPC分类号： C07D487/08
CPC分类号： C07D487/06 , C07D213/56 , C07D239/95 , C07D401/04 , C07D401/14 , C07D417/14
摘要： The present invention relates to therapeutic diazobicyclo pyridines and their use in the treatment of arthritis, rheumatoid arthritis, psoriatic arthritis or osteoarthritis, organ transplant, acute transplant or heterograft and homograft rejection, ischemic and reperfusion injury, transplantation tolerance induction, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lupus, graft vs. host diseases, T -cell mediated hypersensitivity diseases, contact hypersensitivity, delayed-type hypersensitivity, gluten-sensitive enteropathy, Type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism,Graves' Disease, Addison's disease, autoimmune polyglandular disease, autoimmune alopecia, pernicious anemia, vitiligo, autoimmune hypopituatarism, Guillain-Barre syndrome, autoimmune diseases, glomerulonephritis, serum sickness, uticaria, respiratory allergies, asthma, hayfever, allergic rhinitis, skin allergies, scleracielma, mycosis fungoides, acute inflammatory responses, acute respiratory distress syndrome, dermatomyositis, alopecia areata, chronic actinic dermatitis, eczema, Behcet's disease, Pustulosis palmoplanteris, Pyoderma gangrenum, Sezary's syndrome, atopic dermatitis, systemic schlerosis, morphea, Type II diabetes and cancers where PKC theta or other PKC-family kinases are activated, overexpressed or facilitate tumor growth or survival of tumor cells, T cell leukemia, thymoma, T and B cell lymphoma, colon carcinoma, breast carcinoma and lung carcinoma or provides resistance to chemotherapeutic drugs.
摘要翻译：本发明涉及治疗性重氮二环吡啶及其在治疗关节炎，类风湿性关节炎，银屑病关节炎或骨关节炎，器官移植，急性移植或异种移植和同种异体移植排斥，缺血和再灌注损伤，移植耐受诱导，多发性硬化，炎性肠中的用途疾病，溃疡性结肠炎，克罗恩病，狼疮，移植物抗宿主病，T细胞介导的超敏反应性疾病，接触性超敏反应，延迟型超敏反应，麸质敏感性肠病，1型糖尿病，牛皮癣，接触性皮炎，桥本氏甲状腺炎，干燥综合征，自身免疫性甲状腺功能亢进症，格雷夫斯病，艾迪生病，自身免疫性多腺病，自身免疫性脱发，恶性贫血，白癜风，自身免疫性低位虚型，吉兰巴利综合征，自身免疫性疾病，肾小球肾炎，血清病，uticaria，呼吸系统过敏，哮喘，过敏性鼻炎，皮肤过敏 s，scleracielma，蕈样真菌病，急性炎症反应，急性呼吸窘迫综合征，皮肌炎，斑秃，慢性光化性皮炎，湿疹，贝切特病，脓疱疮，疱疹性坏疽，Sezary综合征，特应性皮炎，全身性硬化症，morphea，II型糖尿病和其中PKCθ或其他PKC家族激酶被激活，过度表达或促进肿瘤细胞，T细胞白血病，胸腺瘤，T细胞和B细胞淋巴瘤，结肠癌，乳腺癌和肺癌的肿瘤生长或存活的癌症，或提供对化学治疗的抗性药物。

9. 发明申请

WO2004022055A1 1, 4, 5-SUBSTITUTED 1, 2-DIHYDRO-PYRAZOL-3-ONE AND 3-ALKOXY-1H-PYRAZOLE DERIVATIVES S TNF-ALPHA AND INTERLEUKIN LOWERING AGENTS FOR THE TREATMENT OF INFLAMMATIONS 审中-公开
标题翻译： 1,4,5-取代的1,2-二氢吡喃-3-酮和3-烷氧基-1H-吡唑衍生物S TNF-ALPHA和白介素降低剂用于治疗炎症
公开(公告)号：WO2004022055A1
公开(公告)日：2004-03-18
申请号：PCT/US2003/028067
申请日：2003-09-08
申请人： AMGEN INC.
发明人： DOMINGUEZ, Celia , ZHANG, Dawei , SHAM, Kelvin, K. C. , CAO, Guo-Qiang
IPC分类号： A61K31/4152
CPC分类号： C07D401/04 , C07D401/14
摘要： The present invention relates to compounds having the general formula (I) or a pharmaceutically acceptable salt thereof. Also included is a method of prophylaxis or treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis,Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.
摘要翻译：本发明涉及具有通式的化合物或其药学上可接受的盐。还包括预防或治疗炎症，类风湿性关节炎，斑节病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸窘迫综合征（ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉退化，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应，阿尔茨海默病，中风，心肌梗死，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒引起的肌痛（CMV），流感，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的化合物作为de 如上所述。

10. 发明公开

EP2097416A1 AZAQUINOLONE BASED COMPOUNDS EXHIBITING PROLYL HYDROXYLASE INHIBITORY ACTIVITY, COMPOSITIONS, AND USES THEREOF 有权
标题翻译： CONNECTIONS与AZACHINOLONBASIS脯氨酰羟化酶抑制剂的效果组合物及其使用
公开(公告)号：EP2097416A1
公开(公告)日：2009-09-09
申请号：EP07863038.1
申请日：2007-12-17
申请人： Amgen, Inc
发明人： ALLEN, Jennifer R. , BISWAS, Kaustav , CAO, Guo-Qiang , GOLDEN, Jennifer E. , MERCEDE, Stephanie , PETERKIN, Tanya , REED, Anthony , TEGLEY, Christopher M.
IPC分类号： C07D487/04
CPC分类号： C07D471/04
摘要： Compounds of Formula (I) are useful as inhibitors of HIF prolyl hydroxylases where the definitions of the variables are provided herein.

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