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    P2X7 MODULATORS
    2.
    发明公开
    P2X7 MODULATORS 审中-公开
    P2X7调制器

    公开(公告)号：EP3321266A1

    公开(公告)日：2018-05-16

    申请号：EP17200257.8

    申请日：2014-03-14

    申请人： Janssen Pharmaceutica NV

    发明人： ALCAZAR VACA, Manuel Jesus ,  ANDRES GIL, Jose Ignacio ,  LETAVIC, Michael A. ,  RUDOLPH, Dale A. ,  SHIREMAN, Brock T. ,  STENNE, Brice M. ,  ZIFF, Jeannie M.

    IPC分类号： C07D471/04 ,  A61K31/519 ,  A61P25/00 ,  A61P19/00 ,  A61P11/00

    CPC分类号： C07D471/04

    摘要： The present invention is directed to a compound of Formula (I) or (la). The invention also relates to pharmaceutical compositions comprising compounds of Formula (I) or (la) and methods comprising administering of compounds of Formula (I) or (la) for treating rheumatoid arthritis, osteoarthritis, psoriasis, septic shock, allergic dermatitis, asthma, allergic asthma, mild to severe asthma, steroid resistant asthma, idiopathic pulmonary fibrosis, allergic rhinitis, chronic obstructive pulmonary disease; airway hyper-responsiveness, diseases of the nervous and neuroimmune system, acute and chronic pain states of neuropathic pain, inflammatory pain, spontaneous pain, opioid induced pain, diabetic neuropathy, postherpetic neuralgia, low back pain, chemotherapy-induced neuropathic pain, fibromyalgia, diseases involved with and without neuroinflammation of the central nervous system, mood disorders, major depression, major depressive disorder, treatment resistant depression, bipolar disorder, anxious depression, anxiety, cognition, sleep disorders, multiple sclerosis, epileptic seizures, Parkinson's disease, schizophrenia, Alzheimer's disease, Huntington's disease, autism, spinal cord injury and cerebral ischemia/traumatic brain injury, stress-related disorders, diseases of the cardiovascular, metabolic, gastrointestinal and urogenital systems such as diabetes, diabetes mellitus, thrombosis, irritable bowel syndrome, irritable bowel disease, Crohn's disease, ischemic heart disease, ischaemia, hypertension, cardiovascular disease, myocardial infarction, and lower urinary tract dysfunction such as incontinence, lower urinary tract syndrome, Polycystic Kidney Disease, Glomemlonephritis, skeletal disorders, osteoporosis, osteopetrosis, and glaucoma, interstitial cystitis, cough, ureteric obstruction, sepsis, Amyotrophic Lateral Sclerosis, Chaga's Disease, chlamydia, neuroblastoma, Tuberculosis, and migraine.

    摘要翻译： 本发明涉及式（I）或（Ia）的化合物。 本发明还涉及包含式（I）或（Ia）化合物的药物组合物以及包括给予式（I）或（Ia）化合物用于治疗类风湿性关节炎，骨关节炎，牛皮癣，败血性休克，过敏性皮炎，哮喘， 过敏性哮喘，轻至重度哮喘，类固醇抗性哮喘，特发性肺纤维化，变应性鼻炎，慢性阻塞性肺病; 气道高反应性，神经和免疫系统疾病，神经性疼痛的急性和慢性疼痛状态，炎性疼痛，自发性疼痛，阿片样物质诱导的疼痛，糖尿病性神经病，带状疱疹后神经痛，腰背痛，化学疗法引起的神经性疼痛，纤维肌痛， 与中枢神经系统神经炎症相关的疾病，情绪障碍，重性抑郁症，重度抑郁症，治疗抵抗性抑郁症，双相情感障碍，焦虑抑郁症，焦虑症，认知障碍，睡眠障碍，多发性硬化症，癫痫发作，帕金森氏症，精神分裂症， 阿尔茨海默病，亨廷顿病，自闭症，脊髓损伤和脑缺血/创伤性脑损伤，压力相关病症，心血管疾病，代谢病，胃肠和泌尿生殖系统如糖尿病，糖尿病，血栓形成，肠易激综合征，肠易激 疾病，克罗恩氏病，缺血性心脏病，ischaem 心律失常，下尿路综合征，多囊肾病，肾小球肾炎，骨骼疾病，骨质疏松症，骨硬化症和青光眼，间质性膀胱炎，咳嗽，输尿管梗阻，脓毒症， 肌萎缩侧索硬化症，Chaga氏病，衣原体，神经母细胞瘤，结核病和偏头痛。

    P2X7 MODULATORS
    10.
    发明授权
    P2X7 MODULATORS 有权

    公开(公告)号：EP2970287B1

    公开(公告)日：2017-11-01

    申请号：EP14721097.5

    申请日：2014-03-14

    申请人： Janssen Pharmaceutica NV

    发明人： LETAVIC, Michael A. ,  RUDOLPH, Dale A.

    IPC分类号： C07D471/18 ,  C07D487/18 ,  C07D498/18 ,  A61K31/553 ,  A61K31/4995 ,  A61P19/00 ,  A61P11/06 ,  A61P17/06 ,  A61P29/00 ,  A61P25/00 ,  A61P9/00

    CPC分类号： C07D471/18 ,  A61P25/00 ,  C07D471/08 ,  C07D487/18 ,  C07D498/18

    摘要： The present invention is directed to a compound of Formula (I): wherein: n is an integer from 0-1; €¢ X is CH 2 when n is 0, or X is CH 2 or oxygen when n is 1; €¢ R 1 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is optionally substituted with from 1 to 4 substituents independently selected from halogen and alkyl; and €¢ R 2 is phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl, wherein the phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl is optionally substituted with from 1 to 2 substituents independently selected from the group consisting of halogen, alkyl, hydroxy and alkoxy. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). The compounds of formula (I) are useful as P2X7 modulators.