公开(公告)号：US07893064B2

公开(公告)日：2011-02-22

申请号：US11871472

申请日：2007-10-12

申请人： Guozhang Xu ,  Lily Lee Searle ,  Shenlin Huang

发明人： Guozhang Xu ,  Lily Lee Searle ,  Shenlin Huang

IPC分类号： C07D403/12 ,  A61K31/506

CPC分类号： C07D403/12

摘要： The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I) or a form or composition thereof as inhibitors of ATP-protein kinase interactions, wherein substituents on each side of the iminomethyl double bond in Formula (I) may be in the E or Z configuration; and wherein R1, R2, R3 and R4 are as defined herein.

摘要翻译： 本发明涉及式（I）的新型双环嘧啶化合物或其形式或组成作为ATP-蛋白激酶相互作用的抑制剂，其中式（I）中亚氨基甲基双键各侧的取代基可以在E 或Z配置; 并且其中R 1，R 2，R 3和R 4如本文所定义。

公开(公告)号：US08344009B2

公开(公告)日：2013-01-01

申请号：US12899812

申请日：2010-10-07

申请人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond Patch ,  Dionisois Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

发明人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond Patch ,  Dionisois Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

IPC分类号： A61K31/426 ,  C07D277/04

CPC分类号： C07D277/34 ,  C07D263/44

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US20110237625A1

公开(公告)日：2011-09-29

申请号：US12899812

申请日：2010-10-07

申请人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond J. Patch ,  Dionisios Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

发明人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond J. Patch ,  Dionisios Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

IPC分类号： A61K31/454 ,  C07D277/34 ,  A61K31/426 ,  C07D263/44 ,  A61K31/421 ,  A61P19/00 ,  A61P11/00 ,  A61P35/00 ,  A61P3/00 ,  A61P9/12

CPC分类号： C07D277/34 ,  C07D263/44

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖症，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US07846953B2

公开(公告)日：2010-12-07

申请号：US12043269

申请日：2008-03-06

申请人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond Patch ,  Dionisois Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

发明人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond Patch ,  Dionisois Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

IPC分类号： A61K31/426 ,  C07D277/04

CPC分类号： C07D277/34 ,  C07D263/44

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖症，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US20090111855A1

公开(公告)日：2009-04-30

申请号：US12043269

申请日：2008-03-06

申请人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond J. Patch ,  Dionisios Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

发明人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Raymond J. Patch ,  Dionisios Rentzeperis ,  Guozhang Xu ,  Xizhen Zhu

IPC分类号： A61K31/454 ,  C07D277/34 ,  A61K31/426 ,  A61K31/421 ,  C07D263/44 ,  A61P3/04

CPC分类号： C07D277/34 ,  C07D263/44

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US09034852B2

公开(公告)日：2015-05-19

申请号：US13346808

申请日：2012-01-10

申请人： Michael Gaul ,  Lily Lee Searle ,  Dionisios Rentzeperis

发明人： Michael Gaul ,  Lily Lee Searle ,  Dionisios Rentzeperis

IPC分类号： C07D277/34 ,  C07D417/06

CPC分类号： C07D277/34 ,  C07D417/06

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US08580832B2

公开(公告)日：2013-11-12

申请号：US12043311

申请日：2008-03-06

申请人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Dionisios Rentzeperis ,  Gilles C. Bignan

发明人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Dionisios Rentzeperis ,  Gilles C. Bignan

IPC分类号： A61K31/425 ,  C07D277/08 ,  C07D277/12

CPC分类号： C07D277/34 ,  C07D417/04

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖症，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US20080286265A1

公开(公告)日：2008-11-20

申请号：US12043291

申请日：2008-03-06

申请人： Michael Gaul ,  Lily Lee Searle ,  Dionisios Rentzeperis

发明人： Michael Gaul ,  Lily Lee Searle ,  Dionisios Rentzeperis

IPC分类号： A61K39/395 ,  C07D417/06 ,  A61K31/5377 ,  A61P19/00 ,  A61P3/00 ,  A61K31/454 ,  A61P35/04 ,  A61K31/427 ,  A61K31/55

CPC分类号： C07D277/34 ,  C07D417/06

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖症，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US20080221179A1

公开(公告)日：2008-09-11

申请号：US12043311

申请日：2008-03-06

申请人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Dionisios Rentzeperis ,  Gilles C. Bignan

发明人： Michael Gaul ,  Alexander Kim ,  Lily Lee Searle ,  Dionisios Rentzeperis ,  Gilles C. Bignan

IPC分类号： A61K31/426 ,  C07D277/56 ,  A61P19/00 ,  A61P11/00 ,  A61P35/04 ,  A61P3/00

CPC分类号： C07D277/34 ,  C07D417/04

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性，软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性血糖，脂质障碍，代谢综合征，多发性 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖症，升高的血糖水平和胰岛素抵抗。

公开(公告)号：US20120108571A1

公开(公告)日：2012-05-03

申请号：US13346808

申请日：2012-01-10

申请人： Michael Gaul ,  Lily Lee Searle ,  Dionisios Rentzeperis

发明人： Michael Gaul ,  Lily Lee Searle ,  Dionisios Rentzeperis

IPC分类号： A61K31/5377 ,  A61K31/496 ,  A61K31/454 ,  A61K31/55 ,  A61P19/08 ,  A61P19/06 ,  A61P19/10 ,  A61P35/04 ,  A61P35/00 ,  A61P19/02 ,  A61P1/02 ,  A61P29/00 ,  A61P11/08 ,  A61P11/00 ,  A61P3/00 ,  A61P3/04 ,  A61P3/10 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  A61P3/08 ,  A61P5/48 ,  A61K31/426

CPC分类号： C07D277/34 ,  C07D417/06

摘要： The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

摘要翻译： 本发明涉及式（I）化合物，制备这些化合物的方法，组合物，中间体及其衍生物，用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿性关节炎，感染性关节炎，儿童期 关节炎，牛皮癣关节炎，反应性关节炎），骨相关疾病（包括与骨形成相关的疾病），乳腺癌（包括对抗雌激素治疗无反应的那些），心血管疾病，软骨相关疾病（如软骨损伤/损失， 软骨变性和与软骨形成相关的软骨变性），软骨发育不全，软骨肉瘤，慢性背部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺病，糖尿病，能量稳态障碍，痛风，假性呕吐，脂质障碍，代谢综合征 骨髓瘤，肥胖症，骨关节炎，成骨不全，骨质溶解骨 骨质疏松症，骨质疏松症，佩吉特氏病，牙周病，风湿性多肌痛，莱特综合征，重复性应激损伤，高血糖，升高的血糖水平和胰岛素抵抗。