公开(公告)号：US08580795B2

公开(公告)日：2013-11-12

申请号：US13143480

申请日：2010-01-21

申请人： Gopalan Balasubramanian ,  Sukunath Narayanan ,  Ganapavarapu Veera Raghava Sharma ,  Lavanya Andiappan ,  Shridhar Narayanan ,  Sanjeev Saxena ,  Sridharan Rajagopal ,  Santosh Lolaknath Vishwakarma ,  Saravanan Thirunavukkarasu

发明人： Gopalan Balasubramanian ,  Sukunath Narayanan ,  Ganapavarapu Veera Raghava Sharma ,  Lavanya Andiappan ,  Shridhar Narayanan ,  Sanjeev Saxena ,  Sridharan Rajagopal ,  Santosh Lolaknath Vishwakarma ,  Saravanan Thirunavukkarasu

IPC分类号： A61K31/496 ,  C07D405/14

CPC分类号： C07D413/04 ,  C07D417/04 ,  C07D417/14

摘要： Compounds of the formula (I), their derivatives, analogs, tautomeric forms, regioisomers, stereoisomers, polymorphs, solvates, intermediates, pharmaceutically acceptable salts, pharmaceutical compositions, N-oxides, metabolites and prodrugs thereof. These compounds are phosphodiesterase type 4 (PDE4) inhibitors. They are useful in the treatment of a variety of allergic or inflammatory diseases including asthma, COPD, chronic bronchitis, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, vernal conjuctivitis, psoriasis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, uveitis, NASH and lupus.

摘要翻译： 式（I）化合物，其衍生物，类似物，互变异构体，区域异构体，立体异构体，多晶型物，溶剂合物，中间体，药学上可接受的盐，药物组合物，N-氧化物，代谢物和前药。 这些化合物是磷酸二酯酶4型（PDE4）抑制剂。 它们可用于治疗各种过敏或炎性疾病，包括哮喘，COPD，慢性支气管炎，特应性皮炎，过敏性鼻炎，过敏性结膜炎，春季结膜炎，牛皮癣，类风湿性关节炎，溃疡性结肠炎，克罗恩病，葡萄膜炎，NASH和狼疮 。

公开(公告)号：US20110269753A1

公开(公告)日：2011-11-03

申请号：US13143480

申请日：2010-01-21

申请人： Gopalan Balasubramanian ,  Sukunath Narayanan ,  Ganapavarapu Veera Raghava Sharma ,  Lavanya Andiappan ,  Shridhar Narayanan ,  Sanjeev Saxena ,  Sridharan Rajagopal ,  Santosh Lolaknath Vishwakarma ,  Saravanan Thirunavukkarasu

发明人： Gopalan Balasubramanian ,  Sukunath Narayanan ,  Ganapavarapu Veera Raghava Sharma ,  Lavanya Andiappan ,  Shridhar Narayanan ,  Sanjeev Saxena ,  Sridharan Rajagopal ,  Santosh Lolaknath Vishwakarma ,  Saravanan Thirunavukkarasu

IPC分类号： A61K31/4439 ,  C07D407/10 ,  C07D403/14 ,  C07D405/14 ,  C07D413/10 ,  C07D413/14 ,  C07D498/04 ,  C07D498/14 ,  A61K31/427 ,  A61K31/506 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/422 ,  A61K31/423 ,  A61K31/437 ,  A61P29/00 ,  A61P37/00 ,  A61P11/06 ,  A61P11/00 ,  A61P11/08 ,  A61P17/00 ,  A61P27/14 ,  A61P17/06 ,  A61P1/04 ,  A61P1/00 ,  A61P27/02 ,  A61P19/04 ,  C07D417/14

CPC分类号： C07D413/04 ,  C07D417/04 ,  C07D417/14

摘要： Compounds of the formula (I), their derivatives, analogs, tautomeric forms, regioisomers, stereoisomers, polymorphs, solvates, intermediates, pharmaceutically acceptable salts, pharmaceutical compositions, N-oxides, metabolites and prodrugs thereof. These compounds are phosphodiesterase type 4 (PDE4) inhibitors. They are useful in the treatment of a variety of allergic or inflammatory diseases including asthma, COPD, chronic bronchitis, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, psoriasis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, uveitis, NASH and lupus.

摘要翻译： 式（I）化合物，其衍生物，类似物，互变异构体，区域异构体，立体异构体，多晶型物，溶剂合物，中间体，药学上可接受的盐，药物组合物，N-氧化物，代谢物和前药。 这些化合物是磷酸二酯酶4型（PDE4）抑制剂。 它们可用于治疗各种过敏或炎性疾病，包括哮喘，COPD，慢性支气管炎，特应性皮炎，过敏性鼻炎，过敏性结膜炎，春季结膜炎，牛皮癣，类风湿性关节炎，溃疡性结肠炎，克罗恩病，葡萄膜炎，NASH和狼疮 。

公开(公告)号：US20080221103A1

公开(公告)日：2008-09-11

申请号：US12073635

申请日：2008-03-07

申请人： Ganapavarapu V.R. Sharma ,  Gaddam O. Reddy ,  Sriram Rajagopal ,  Uma Ramachandran ,  Sukunath Narayanan ,  Nagalakshmi Pichika ,  Venkatesh Nemmara Viswanathan ,  Lavanya Andiappan ,  Saravanan Thirunavukkarasu

发明人： Ganapavarapu V.R. Sharma ,  Gaddam O. Reddy ,  Sriram Rajagopal ,  Uma Ramachandran ,  Sukunath Narayanan ,  Nagalakshmi Pichika ,  Venkatesh Nemmara Viswanathan ,  Lavanya Andiappan ,  Saravanan Thirunavukkarasu

IPC分类号： A61K31/5377 ,  C07D239/24 ,  C07D413/14 ,  A61K31/435 ,  A61P37/06

CPC分类号： C07D239/24 ,  C07D413/14

摘要： Provided herein are heterocyclic compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof, wherein R1, R2, R3, R4 and R5 are as described herein. Further described herein in particular are heterocyclic compounds of the formula (I) for treating various diseases. and disorders by administering in a patient one or more TNF-α, Thromboxane synthase, 5-LOX, and PDE4 inhibitors. In particular described herein are methods for treating immunological diseases, inflammation, pain disorder, rheumatoid arthritis; osteoporosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; ischemic heart disease; atherosclerosis; cancer; ischemic-induced cell damage; pancreatic beta 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; muscle degeneration; cachexia; asthma; bone resorption diseases; ischemia reperfusion injury; brain trauma; multiple sclerosis; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection and diseases mediated by HIV-1; HIV-2; HIV-3; cytomegalovirus (CMV); influenza; adenovirus; the herpes viruses (including HSV-1, HSV-2) and herpes zoster viruses in a mammal comprising administering an effective amount of a compound of formula (I).

摘要翻译： 本文提供了通式（I）的杂环化合物，其衍生物，类似物，互变异构形式，立体异构体，多晶型物，水合物，溶剂合物，药学上可接受的盐和组合物，其代谢物和前药，其中R 1， R 2，R 3，R 4和R 5如本文所述。 本文进一步描述的是用于治疗各种疾病的式（I）的杂环化合物。 以及通过在患者中施用一种或多种TNF-α，血栓烷合成酶，5-LOX和PDE4抑制剂的障碍。 本文特别描述的是用于治疗免疫疾病，炎症，疼痛障碍，类风湿性关节炎的方法; 骨质疏松症 多发性骨髓瘤 葡萄膜炎 急性和慢性粒细胞白血病; 缺血性心脏病; 动脉粥样硬化 癌症; 缺血诱导的细胞损伤; 胰腺β细胞破坏; 骨关节炎 类风湿性脊柱炎; 痛风性关节炎 炎症性肠病; 成人呼吸窘迫综合征（ARDS）; 银屑病; 克罗恩病; 过敏性鼻炎; 溃疡性结肠炎 过敏反应 接触性皮炎; 肌肉退化; 恶病质 哮喘; 骨吸收疾病; 缺血再灌注损伤; 脑外伤; 多发性硬化症 脓毒症 败血性休克 中毒性休克综合征; 发热和由于HIV-1介导的感染和疾病引起的肌痛; HIV-2; HIV-3; 巨细胞病毒（CMV）; 流感; 腺病毒 哺乳动物中的疱疹病毒（包括HSV-1，HSV-2）和带状疱疹病毒，包括施用有效量的式（I）化合物。