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    Substituted heterocyclic compounds and methods of use
    2.
    发明授权
    Substituted heterocyclic compounds and methods of use 有权
    取代的杂环化合物及其使用方法

    公开(公告)号：US07026326B2

    公开(公告)日：2006-04-11

    申请号：US10438553

    申请日：2003-05-13

    申请人： Guo-Qiang Cao ,  Celia Dominguez ,  Martin H. Goldberg ,  Fang-Tsao Hong ,  Kelvin K. C. Sham ,  Seifu Tadesse ,  Nuria A. Tamayo ,  Kurt E. Weiler ,  Dawei Zhang ,  Hongyu Liao

    发明人： Guo-Qiang Cao ,  Celia Dominguez ,  Martin H. Goldberg ,  Fang-Tsao Hong ,  Kelvin K. C. Sham ,  Seifu Tadesse ,  Nuria A. Tamayo ,  Kurt E. Weiler ,  Dawei Zhang ,  Hongyu Liao

    IPC分类号： A61K31/505

    CPC分类号： C07D401/04

    摘要： The present invention relates to compounds having the general formula or a pharmaceutically acceptable salt thereof, wherein R1 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 R1 is additionally substituted; and R2 is a substituted C1-6alkyl. 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，其中R 1是饱和或不饱和的5-，6-或7-元环，其含有0,1,2或 3个选自N，O和S的原子，其中环可以与苯并稠合，并被0,1或2个氧代基取代，并且其中R 1是另外被取代的; 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，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d 以上所述。

    Phthalazine compounds as p38 map kinase modulators and methods of use thereof
    4.
    发明授权
    Phthalazine compounds as p38 map kinase modulators and methods of use thereof 有权
    酞嗪化合物作为p38映射激酶调节剂及其使用方法

    公开(公告)号：US08497269B2

    公开(公告)日：2013-07-30

    申请号：US13123889

    申请日：2009-10-07

    申请人： Andrew Tasker ,  James R. Falsey ,  Robert M. Rzasa ,  Bradley J. Herberich ,  Dawei Zhang

    发明人： Andrew Tasker ,  James R. Falsey ,  Robert M. Rzasa ,  Bradley J. Herberich ,  Dawei Zhang

    IPC分类号： C07D487/04 ,  A61K31/50 ,  A01N43/58

    CPC分类号： C07D401/12 ,  C07D237/30 ,  C07D237/32 ,  C07D237/34 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

    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 A4, L, R1, R2, R3, R5 and m are as 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 p38 map kinase mediated diseases including rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disease, ankylosing spondylitis, pain and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

    摘要翻译： 本发明包括一类新的可用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关病症的化合物。 该化合物具有通式I，其中A4，L，R1，R2，R3，R5和m如本文所定义。 本发明还包括药物组合物，其包含一种或多种式I化合物，用于治疗p38地图激酶介导的疾病包括类风湿性关节炎，牛皮癣，慢性阻塞性肺病，强直性脊柱炎，疼痛和其它炎症性疾病的化合物和组合物的用途，如 以及可用于制备式I化合物的中间体和方法。

    Substituted heterocyclic compounds and methods of use
    6.
    发明授权
    Substituted heterocyclic compounds and methods of use 失效
    取代的杂环化合物及其使用方法

    公开(公告)号：US06967254B2

    公开(公告)日：2005-11-22

    申请号：US10658298

    申请日：2003-09-08

    申请人： Celia Dominguez ,  Dawei Zhang ,  Kelvin K. C. Sham ,  Guo-Qiang Cao

    发明人： Celia Dominguez ,  Dawei Zhang ,  Kelvin K. C. Sham ,  Guo-Qiang Cao

    IPC分类号： C07D401/04 ,  C07D401/14

    CPC分类号： C07D401/04 ,  C07D401/14

    摘要： The present invention relates to compounds having the general formula 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d 以上所述。

    Substituted heterocyclic compounds and methods of use
    7.
    发明申请
    Substituted heterocyclic compounds and methods of use 审中-公开
    取代的杂环化合物及其使用方法

    公开(公告)号：US20090149468A1

    公开(公告)日：2009-06-11

    申请号：US12322671

    申请日：2009-02-04

    申请人： Guo-Qiang Cao ,  Jian J. Chen ,  Celia Dominguez ,  Anthony Reed ,  Kelvin K.C. Sham ,  Maya C. Thaman ,  Dawei Zhang ,  Bradley J. Herberich

    发明人： Guo-Qiang Cao ,  Jian J. Chen ,  Celia Dominguez ,  Anthony Reed ,  Kelvin K.C. Sham ,  Maya C. Thaman ,  Dawei Zhang ,  Bradley J. Herberich

    IPC分类号： A61K31/497 ,  C07D401/14 ,  A61K31/496

    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，自身免疫性低分化症，吉兰巴利综合征，自身免疫性疾病，肾小球肾炎，血清病，荨麻疹，呼吸道过敏，哮喘，过敏性鼻炎，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，白塞病，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

    Substituted heterocyclic compounds and methods of use
    8.
    发明申请
    Substituted heterocyclic compounds and methods of use 有权
    取代的杂环化合物及其使用方法

    公开(公告)号：US20050182072A1

    公开(公告)日：2005-08-18

    申请号：US11034042

    申请日：2005-01-11

    申请人： Guo-Qiang Cao ,  Jian Chen ,  Celia Dominguez ,  Anthony Reed ,  Kelvin Sham ,  Maya Thaman ,  Dawei Zhang ,  Bradley Herberich

    发明人： Guo-Qiang Cao ,  Jian Chen ,  Celia Dominguez ,  Anthony Reed ,  Kelvin Sham ,  Maya Thaman ,  Dawei Zhang ,  Bradley Herberich

    IPC分类号： C07D213/56 ,  C07D239/95 ,  C07D401/04 ,  C07D401/14 ,  C07D417/14 ,  C07D487/06 ,  C07D487/08 ,  C07D519/00 ,  A61K31/519 ,  A61K31/416 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/513 ,  A61K31/517 ,  C07D487/02

    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 flugoides, 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，自身免疫性低分化症，吉兰巴利综合征，自身免疫性疾病，肾小球肾炎，血清病，荨麻疹，呼吸道过敏，哮喘，过敏性鼻炎，过敏性鼻炎 ，皮肤过敏 es，scleracielma，真菌性感冒，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，Behcet氏病，脓疱疮，新生皮炎，Sezary综合征，特应性皮炎，全身性硬化症，morphea，II型糖尿病 和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

    Quinolines for the treatment of PI3K-δ mediated diseases
    10.
    发明授权
    Quinolines for the treatment of PI3K-δ mediated diseases 有权
    喹诺酮用于治疗PI3K-δ介导的疾病

    公开(公告)号：US08329910B2

    公开(公告)日：2012-12-11

    申请号：US13187188

    申请日：2011-07-20

    申请人： Yi Chen ,  Timothy D. Cushing ,  Xiaolin Hao ,  Xiao He ,  Andreas Reichelt ,  Robert M. Rzasa ,  Jennifer Seganish ,  Youngsook Shin ,  Dawei Zhang

    发明人： Yi Chen ,  Timothy D. Cushing ,  Xiaolin Hao ,  Xiao He ,  Andreas Reichelt ,  Robert M. Rzasa ,  Jennifer Seganish ,  Youngsook Shin ,  Dawei Zhang

    IPC分类号： C07D215/12

    CPC分类号： C07D401/12 ,  C07D401/14

    摘要： Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity. The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including nut not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

    摘要翻译： 取代的双环杂芳基和含有它们的组合物，用于治疗一般炎症，关节炎，风湿性疾病，骨关节炎，炎性肠病，炎症性眼病，炎症性或不稳定性膀胱病，牛皮癣，皮肤炎症成分的投诉，慢性炎性病症 不限于自身免疫性疾病如系统性红斑狼疮（SLE），重症肌无力，类风湿关节炎，急性播散性脑脊髓炎，特发性血小板减少性紫癜，多发性硬化症，Sjoegren综合征和自身免疫性溶血性贫血，包括所有形式的超敏反应的过敏症状。 本发明还使得能够治疗依赖于p110δ活性或与p110δ活性相关的癌症的方法，包括不限于白血病的坚果，例如急性骨髓性白血病（AML）Myelo-dysplastic综合征（MDS）骨髓增殖性疾病（MPD） 慢性骨髓性白血病（CML）T细胞急性淋巴细胞白血病（T-ALL）B细胞急性淋巴细胞白血病（B-ALL）非霍奇金淋巴瘤（NHL）B细胞淋巴瘤和实体瘤如乳腺癌。