公开(公告)号：US10239849B2

公开(公告)日：2019-03-26

申请号：US15774157

申请日：2016-11-07

申请人： Merck Sharp & Dohme Corp. ,  Michael T. Rudd ,  Edward J. Brnardic ,  Yuntae Kim ,  Robert S. Meissner ,  Vanessa L. Rada ,  Shawn J. Stachel ,  Celina V. Zerbinatti

发明人： Michael T. Rudd ,  Edward J. Brnardic ,  Yuntae Kim ,  Robert S. Meissner ,  Vanessa L. Rada ,  Shawn J. Stachel ,  Celina V. Zerbinatti

IPC分类号： C07D243/08 ,  C07D295/16 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/08 ,  C07D487/08 ,  C07D513/04 ,  A61P25/18 ,  A61P25/16 ,  A61P25/28 ,  A61P3/10

摘要： In its many embodiments, the present invention provides substituted cyanopyridine containing compounds of the Formula (I): and acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, Q, and the moiety are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US20180327374A1

公开(公告)日：2018-11-15

申请号：US15774157

申请日：2016-11-07

申请人： Michael T. RUDD ,  Edward J. BRNARDIC ,  Yuntae KIM ,  Robert S. MEISSNER ,  Vanessa RADA ,  Shawn J. STACHEL ,  Celina V. ZERBINATTI ,  Merck Sharp & Dohme Corp.

发明人： Michael T. Rudd ,  Edward J. Brnardic ,  Yuntae Kim ,  Robert S. Meissner ,  Vanessa L. Rada ,  Shawn J. Stachel ,  Celina V. Zerbinatti

IPC分类号： C07D295/16 ,  C07D243/08 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/08 ,  C07D487/08 ,  C07D513/04 ,  A61P25/28 ,  A61P25/18 ,  A61P25/16 ,  A61P3/10

CPC分类号： C07D295/16 ,  A61K31/496 ,  A61P3/10 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  C07D213/74 ,  C07D213/85 ,  C07D243/08 ,  C07D295/192 ,  C07D295/205 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/08 ,  C07D487/08 ,  C07D487/18 ,  C07D513/04 ,  C07D515/04

摘要： In its many embodiments, the present invention provides substituted cyanopyridine containing compounds of the Formula (I): and acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, Q, and the moiety are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US07268153B2

公开(公告)日：2007-09-11

申请号：US11145490

申请日：2005-06-03

申请人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

发明人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

IPC分类号： A61K31/165

CPC分类号： C07D295/205 ,  C07C233/13 ,  C07C235/34 ,  C07C255/60 ,  C07C271/12 ,  C07C271/22 ,  C07C2601/02 ,  C07D213/61 ,  C07D213/73

摘要： Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式I的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强弱化肌张力和治疗由雄激素缺乏引起的疾病或可由雄激素给药改善的疾病，包括骨质疏松症，骨质减少，糖皮质激素诱导的骨质疏松症，牙周病，骨折，骨重建后的骨损伤 手术，肌营养不良，虚弱，老化的皮肤，男性性腺机能减退，女性绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生 ），腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默氏病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰以及自身免疫性疾病，单独或与其它活性剂组合。

公开(公告)号：US07763659B2

公开(公告)日：2010-07-27

申请号：US11712727

申请日：2007-03-01

申请人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

发明人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

IPC分类号： A61K31/165

CPC分类号： C07D295/205 ,  C07C233/13 ,  C07C235/34 ,  C07C255/60 ,  C07C271/12 ,  C07C271/22 ,  C07C2601/02 ,  C07D213/61 ,  C07D213/73

摘要： Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式I的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强弱化肌张力和治疗由雄激素缺乏引起的疾病或可由雄激素给药改善的疾病，包括骨质疏松症，骨质减少，糖皮质激素诱导的骨质疏松症，牙周病，骨折，骨重建后的骨损伤 手术，肌营养不良，虚弱，老化的皮肤，男性性腺机能减退，女性绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生 ），腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默氏病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰以及自身免疫性疾病，单独或与其它活性剂组合。

公开(公告)号：US20090275515A1

公开(公告)日：2009-11-05

申请号：US12442581

申请日：2007-10-15

申请人： Yuntae Kim ,  Robert S. Meissner ,  Helen J. Mitchell ,  James J. Perkins ,  Michael A. Rossi ,  Jiabing Wang

发明人： Yuntae Kim ,  Robert S. Meissner ,  Helen J. Mitchell ,  James J. Perkins ,  Michael A. Rossi ,  Jiabing Wang

IPC分类号： A61K31/44 ,  C07D213/56 ,  C07D409/12 ,  C07D401/12 ,  A61K31/4365 ,  A61K31/437 ,  A61P19/00 ,  A61K31/565 ,  A61K38/29 ,  A61K38/27 ,  A61K31/59 ,  A61P35/00

CPC分类号： C07D213/40 ,  C07D409/12

摘要： Compounds of structural formula (I) are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HFV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式（I）的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强弱化肌张力和治疗由雄激素缺乏引起的疾病或可由雄激素给药改善的疾病，包括骨质疏松症，骨质减少，糖皮质激素诱导的骨质疏松症，牙周病，骨折，骨重建后的骨损伤 手术，肌肉减少症，虚弱，衰老皮肤，男性性腺机能减退，女性绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎性关节炎和关节修复，HFV消耗，前列腺癌，良性前列腺增生 ），腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默氏病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰以及自身免疫性疾病，单独或与其它活性剂组合。

公开(公告)号：US20080139630A1

公开(公告)日：2008-06-12

申请号：US11628685

申请日：2005-06-03

申请人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

发明人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

IPC分类号： A61K31/44 ,  A61P35/00 ,  C07C233/00 ,  C07D211/80 ,  A61K31/165

CPC分类号： C07D295/205 ,  C07C233/13 ,  C07C235/34 ,  C07C255/60 ,  C07C271/12 ,  C07C271/22 ,  C07C2601/02 ,  C07D213/61 ,  C07D213/73

摘要： Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式I的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强减弱的肌肉紧张度和治疗由雄激素缺乏引起的或由雄激素施用引起的疾病的治疗，包括骨质疏松症，骨质减少症，糖皮质激素诱导的骨质疏松症，牙周病骨折，骨重建手术后的骨损伤 ，肌肉减少症，虚弱，老化的皮肤，男性性腺机能减退，妇女绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎症性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生症（BPH） ，腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰，以及自身免疫疾病，单独或与其他活性剂组合。

公开(公告)号：US20090088458A1

公开(公告)日：2009-04-02

申请号：US11989412

申请日：2006-07-28

申请人： Robert S. Meissner ,  James J. Perkins ,  Yuntae Kim ,  Barbara Hanney ,  Carol A. McVean

发明人： Robert S. Meissner ,  James J. Perkins ,  Yuntae Kim ,  Barbara Hanney ,  Carol A. McVean

IPC分类号： A61K31/4418 ,  C07D213/36 ,  A61P19/02 ,  A61K38/27 ,  C07D213/63

CPC分类号： C07D213/61 ,  A61K31/44 ,  C07D213/64 ,  C07D213/65 ,  Y02A50/401

摘要： Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式I的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强弱化肌张力和治疗由雄激素缺乏引起的疾病或可由雄激素给药改善的疾病，包括骨质疏松症，骨质减少，糖皮质激素诱导的骨质疏松症，牙周病，骨折，骨重建后的骨损伤 手术，肌营养不良，虚弱，老化的皮肤，男性性腺机能减退，女性绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生 ），腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默氏病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰以及自身免疫性疾病，单独或与其它活性剂组合。

公开(公告)号：US20080124402A1

公开(公告)日：2008-05-29

申请号：US11666525

申请日：2005-10-25

申请人： Yuntae Kim ,  Joshua Close ,  Mark E. Duggan ,  Barbara Hanney ,  Robert S. Meissner ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

发明人： Yuntae Kim ,  Joshua Close ,  Mark E. Duggan ,  Barbara Hanney ,  Robert S. Meissner ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

IPC分类号： A61K33/16 ,  C07D213/02 ,  A61K31/44 ,  A61K31/56 ,  A61K38/16 ,  A61K31/59 ,  A61P19/10 ,  A61P19/08 ,  A61K31/66 ,  A61K31/4535 ,  A61K33/10 ,  A61K33/06

CPC分类号： C07D213/64 ,  A61K31/44 ,  C07D213/74

摘要： Compounds of structural formula (I) are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式（I）的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强弱化肌张力和治疗由雄激素缺乏引起的疾病或可由雄激素给药改善的疾病，包括骨质疏松症，骨质减少，糖皮质激素诱导的骨质疏松症，牙周病，骨折，骨重建后的骨损伤 手术，肌营养不良，虚弱，老化的皮肤，男性性腺机能减退，女性绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生 ），腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默氏病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰以及自身免疫性疾病，单独或与其它活性剂组合。

公开(公告)号：US07629367B2

公开(公告)日：2009-12-08

申请号：US11628685

申请日：2005-06-03

申请人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

发明人： Barbara Hanney ,  Yuntae Kim ,  Michael R. Krout ,  Robert S. Meissner ,  Helen J. Mitchell ,  Jeffrey Musselman ,  James J. Perkins ,  Jiabing Wang

IPC分类号： A61K31/165

CPC分类号： C07D295/205 ,  C07C233/13 ,  C07C235/34 ,  C07C255/60 ,  C07C271/12 ,  C07C271/22 ,  C07C2601/02 ,  C07D213/61 ,  C07D213/73

摘要： Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.

摘要翻译： 结构式I的化合物是以组织选择性方式的雄激素受体（AR）的调节剂。 这些化合物可用于增强减弱的肌肉紧张度和治疗由雄激素缺乏引起的或由雄激素施用引起的疾病的治疗，包括骨质疏松症，骨质减少症，糖皮质激素诱导的骨质疏松症，牙周病骨折，骨重建手术后的骨损伤 ，肌肉减少症，虚弱，老化的皮肤，男性性腺机能减退，妇女绝经后症状，动脉粥样硬化，高胆固醇血症，高脂血症，肥胖，再生障碍性贫血和其他造血障碍，炎症性关节炎和关节修复，艾滋病毒消耗，前列腺癌，良性前列腺增生症（BPH） ，腹部肥胖，代谢综合征，II型糖尿病，癌症恶病质，阿尔茨海默病，肌营养不良症，认知衰退，性功能障碍，睡眠呼吸暂停，抑郁症，卵巢早衰，以及自身免疫疾病，单独或与其他活性剂组合。

公开(公告)号：US20170305902A1

公开(公告)日：2017-10-26

申请号：US15506269

申请日：2015-08-24

申请人： Merck Sharp & Dohme Corp. ,  Merck Canada Inc.

发明人： Ashok Arasappan ,  Christopher James Bungard ,  Jessica L. Frie ,  Yongxin Han ,  Scott B. Hoyt ,  Peter J. Manley ,  Robert S. Meissner ,  James J. Perkins ,  Iyassu K. Sebhat ,  Robert R. Wilkening ,  Kenneth J. Leavitt

IPC分类号： C07D471/04

CPC分类号： C07D471/04 ,  A61K31/4375

摘要： The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, L, X1, X2, and X3, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.