公开(公告)号：US08895776B2

公开(公告)日：2014-11-25

申请号：US12933196

申请日：2009-03-17

Applicant: Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J. M. Sadeque ,  Anna Shifrina ,  Young-Jun Shin ,  Pureza Vallar ,  Ning Zou

Inventor： Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J. M. Sadeque ,  Anna Shifrina ,  Young-Jun Shin ,  Pureza Vallar ,  Ning Zou

IPC: C07C241/00 ,  C07C271/12 ,  C07D213/75 ,  C07D241/20 ,  C07D277/48 ,  C07C275/24 ,  C07C275/34 ,  C07C271/28 ,  C07C309/15 ,  C07C275/28 ,  C07C275/30 ,  C07D333/36

CPC classification number: A61K31/195 ,  A61K31/27 ,  A61K31/325 ,  A61K31/381 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4965 ,  C07B2200/07 ,  C07B2200/13 ,  C07C271/12 ,  C07C271/28 ,  C07C275/24 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C309/15 ,  C07C2601/14 ,  C07D213/75 ,  C07D241/20 ,  C07D277/48 ,  C07D333/36

Abstract: The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

Abstract translation: 本发明涉及式（XIIIa）的酰胺衍生物及其调节PGI 2受体活性的药物组合物。 本发明的化合物及其药物组合物涉及可用于治疗肺动脉高压（PAH）的方法; 特发性PAH; 家族性PAH; PAH与胶原血管疾病，先天性心脏病，门静脉高压，HIV感染，摄入药物或毒素，遗传性出血性毛细血管扩张症，脾切除术，肺静脉闭塞性疾病（PVOD）或肺毛细血管血管病变（PCH）有关）。 PAH具有明显的静脉或毛细血管介入; 血小板聚集; 冠状动脉疾病; 心肌梗死; 短暂性脑缺血发作; 心绞痛 行程; 缺血再灌注损伤; 再狭窄; 房颤; 在血管成形术或冠状动脉旁路手术个体或患有心房颤动的个体中血凝块形成; 动脉粥样硬化 动脉粥样硬化血栓形成 哮喘或其症状; 糖尿病性相关疾病如糖尿病性周围神经病变，糖尿病性肾病或糖尿病性视网膜病变; 青光眼或其他眼睛异常眼内疾病; 高血压; 炎; 银屑病; 牛皮癣关节炎 类风湿关节炎; 克罗恩病; 移植排斥反应 多发性硬化症 系统性红斑狼疮（SLE）; 溃疡性结肠炎 缺血再灌注损伤; 再狭窄; 动脉粥样硬化 粉刺; 1型糖尿病; 2型糖尿病; 败血症 和慢性阻塞性肺疾病（COPD）。

公开(公告)号：US20070219252A1

公开(公告)日：2007-09-20

申请号：US11659608

申请日：2005-08-12

Applicant: Weichao Chen ,  Alec Lebsack ,  Benito Munoz ,  Shankar Venkatraman ,  Bowei Wang

Inventor： Weichao Chen ,  Alec Lebsack ,  Benito Munoz ,  Shankar Venkatraman ,  Bowei Wang

IPC: A61K31/44 ,  C07D401/02

CPC classification number: C07K5/06139 ,  C07K5/06191

Abstract: Compounds of Formula (I) are antagonists of VLA-4, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of inflammatory bowel disease including ulcerative colitis and Crohn's disease, multiple sclerosis, asthma, and rheumatoid arthritis.

Abstract translation: 式（I）化合物是VLA-4的拮抗剂，因此可用于抑制或预防细胞粘附和细胞粘附介导的病理学。 这些化合物可以配制成药物组合物，并且适用于治疗包括溃疡性结肠炎和克罗恩病，多发性硬化，哮喘和类风湿性关节炎的炎性肠病。

公开(公告)号：US10894787B2

公开(公告)日：2021-01-19

申请号：US13825601

申请日：2011-09-21

Applicant: Robert M. Jones ,  Juerg Lehmann ,  Weichao Chen ,  Jeffrey Edwards ,  Glen Marquez ,  Michael E. Morgan ,  Abu J. M. Sadeque ,  Sun Hee Kim

Inventor： Robert M. Jones ,  Juerg Lehmann ,  Weichao Chen ,  Jeffrey Edwards ,  Glen Marquez ,  Michael E. Morgan ,  Abu J. M. Sadeque ,  Sun Hee Kim

IPC: A61K38/00 ,  C07D413/14 ,  A61K31/506 ,  A61K45/06

Abstract: The present invention relates to the GPR119 receptor agonists: 3-fluoro-4-(5-fluoro-6-(4-3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)-N,N-imethylbenzamide; 3-fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)-N-methylbenzamide; and 3-fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)benzamide, and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as a single pharmaceutical agent or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPRI19-receptor-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

公开(公告)号：US20150126527A1

公开(公告)日：2015-05-07

申请号：US14510669

申请日：2014-10-09

Applicant: Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J.M. Sadeque ,  Anna Shifrina ,  Young-Jun Shin ,  Pureza Vallar ,  Ning Zou

Inventor： Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J.M. Sadeque ,  Anna Shifrina ,  Young-Jun Shin ,  Pureza Vallar ,  Ning Zou

IPC: A61K31/195 ,  A61K31/4406 ,  A61K31/426 ,  A61K31/4402 ,  A61K31/44 ,  A61K31/4965 ,  A61K31/325 ,  A61K31/381

CPC classification number: A61K31/195 ,  A61K31/27 ,  A61K31/325 ,  A61K31/381 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4965 ,  C07B2200/07 ,  C07B2200/13 ,  C07C271/12 ,  C07C271/28 ,  C07C275/24 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C309/15 ,  C07C2601/14 ,  C07D213/75 ,  C07D241/20 ,  C07D277/48 ,  C07D333/36

Abstract: The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: Pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack, angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

Abstract translation: 本发明涉及式（XIIIa）的酰胺衍生物及其调节PGI 2受体活性的药物组合物。 本发明化合物及其药物组合物涉及用于治疗肺动脉高压（PAH）的方法： 特发性PAH; 家族性PAH; PAH与胶原血管疾病，先天性心脏病，门静脉高压，HIV感染，摄入药物或毒素，遗传性出血性毛细血管扩张症，脾切除术，肺静脉闭塞性疾病（PVOD）或肺毛细血管血管病变（PCH）有关）。 PAH具有明显的静脉或毛细血管介入; 血小板聚集; 冠状动脉疾病; 心肌梗死; 短暂性脑缺血发作，心绞痛; 行程; 缺血再灌注损伤; 再狭窄; 房颤; 在血管成形术或冠状动脉旁路手术个体或患有心房颤动的个体中血凝块形成; 动脉粥样硬化 动脉粥样硬化血栓形成 哮喘或其症状; 糖尿病性相关疾病如糖尿病性周围神经病变，糖尿病性肾病或糖尿病性视网膜病变; 青光眼或其他眼睛异常眼内疾病; 高血压; 炎; 银屑病; 牛皮癣关节炎 类风湿关节炎; 克罗恩病; 移植排斥反应 多发性硬化症 系统性红斑狼疮（SLE）; 溃疡性结肠炎 缺血再灌注损伤; 再狭窄; 动脉粥样硬化 粉刺; 1型糖尿病; 2型糖尿病; 败血症 和慢性阻塞性肺疾病（COPD）。

公开(公告)号：US20130217706A1

公开(公告)日：2013-08-22

申请号：US13614326

申请日：2012-09-13

Applicant: Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J.M. Sadeque ,  Anna Shifrina ,  Yoúng-Jun Shin ,  Pureza Vallar ,  Ning Zou

Inventor： Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J.M. Sadeque ,  Anna Shifrina ,  Yoúng-Jun Shin ,  Pureza Vallar ,  Ning Zou

IPC: C07C271/28 ,  C07C275/28 ,  C07D277/48 ,  C07D333/36 ,  C07C275/34 ,  C07D241/20 ,  C07C275/24 ,  C07D213/75

CPC classification number: A61K31/195 ,  A61K31/27 ,  A61K31/325 ,  A61K31/381 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4965 ,  C07B2200/07 ,  C07B2200/13 ,  C07C271/12 ,  C07C271/28 ,  C07C275/24 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C309/15 ,  C07C2601/14 ,  C07D213/75 ,  C07D241/20 ,  C07D277/48 ,  C07D333/36

Abstract: The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease; and other diseases.

Abstract translation: 本发明涉及式（XIIIa）的酰胺衍生物及其调节PGI 2受体活性的药物组合物。 本发明的化合物及其药物组合物涉及可用于治疗肺动脉高压（PAH）的方法; 特发性PAH; 家族性PAH; 与胶原血管病有关的PAH; 和其他疾病。

公开(公告)号：US20110053958A1

公开(公告)日：2011-03-03

申请号：US12933196

申请日：2009-03-17

Applicant: Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J.M. Sadeque ,  Anna Shifrina ,  Young-Jun Shin ,  Pureza Vallar ,  Ning Zou

Inventor： Thuy-Anh Tran ,  Weichao Chen ,  Bryan A. Kramer ,  Abu J.M. Sadeque ,  Anna Shifrina ,  Young-Jun Shin ,  Pureza Vallar ,  Ning Zou

IPC: A61K31/4965 ,  C07C275/18 ,  C07C275/28 ,  C07C271/28 ,  C07C275/34 ,  C07D213/75 ,  C07D333/36 ,  C07D241/20 ,  C07D277/48 ,  A61K31/196 ,  A61K31/27 ,  A61K31/4406 ,  A61K31/381 ,  A61K31/44 ,  A61K31/426 ,  A61P7/02 ,  A61P9/10 ,  A61P9/00 ,  A61P11/06 ,  A61P3/10 ,  A61P27/02 ,  A61P27/06 ,  A61P9/12 ,  A61P29/00 ,  A61P17/06 ,  A61P19/02 ,  A61P37/06 ,  A61P25/28 ,  A61P11/00

CPC classification number: A61K31/195 ,  A61K31/27 ,  A61K31/325 ,  A61K31/381 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4965 ,  C07B2200/07 ,  C07B2200/13 ,  C07C271/12 ,  C07C271/28 ,  C07C275/24 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C309/15 ,  C07C2601/14 ,  C07D213/75 ,  C07D241/20 ,  C07D277/48 ,  C07D333/36

Abstract: The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

Abstract translation: 本发明涉及式（XIIIa）的酰胺衍生物及其调节PGI 2受体活性的药物组合物。 本发明化合物及其药物组合物涉及用于治疗肺动脉高压（PAH）的方法; 特发性PAH; 家族性PAH; PAH与胶原血管疾病，先天性心脏病，门静脉高压，HIV感染，摄入药物或毒素，遗传性出血性毛细血管扩张症，脾切除术，肺静脉闭塞性疾病（PVOD）或肺毛细血管血管病变（PCH）有关）。 PAH具有明显的静脉或毛细血管介入; 血小板聚集; 冠状动脉疾病; 心肌梗死; 短暂性脑缺血发作; 心绞痛 行程; 缺血再灌注损伤; 再狭窄; 房颤; 在血管成形术或冠状动脉旁路手术个体或患有心房颤动的个体中血凝块形成; 动脉粥样硬化 动脉粥样硬化血栓形成 哮喘或其症状; 糖尿病性相关疾病如糖尿病性周围神经病变，糖尿病性肾病或糖尿病性视网膜病变; 青光眼或其他眼睛异常眼内疾病; 高血压; 炎; 银屑病; 牛皮癣关节炎 类风湿关节炎; 克罗恩病; 移植排斥反应 多发性硬化症 系统性红斑狼疮（SLE）; 溃疡性结肠炎 缺血再灌注损伤; 再狭窄; 动脉粥样硬化 粉刺; 1型糖尿病; 2型糖尿病; 败血症 和慢性阻塞性肺疾病（COPD）。

公开(公告)号：US20140051629A1

公开(公告)日：2014-02-20

申请号：US13825601

申请日：2011-09-21

Applicant: Robert M. Jones ,  Juerg Lehmann ,  Weichao Chen ,  Jeffrey Edwards ,  Glen Marquez ,  Michael E. Morgan ,  Abu J.M. Sadeque ,  Sun Hee Kim

Inventor： Robert M. Jones ,  Juerg Lehmann ,  Weichao Chen ,  Jeffrey Edwards ,  Glen Marquez ,  Michael E. Morgan ,  Abu J.M. Sadeque ,  Sun Hee Kim

IPC: C07D413/14 ,  A61K45/06 ,  A61K31/506

CPC classification number: C07D413/14 ,  A61K31/506 ,  A61K45/06

Abstract: The present invention relates to the GPR119 receptor agonists: 3-fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)-N,N-dimethylbenzamide; -fluoro-4-(5-fluoro-6-(4-(3-(2-fluoro-propan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)-N-methylbenzamide; and 3-fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)benzamide, and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as a single pharmaceutical agent or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

Abstract translation: 本发明涉及GPR119受体激动剂：3-氟-4-（5-氟-6-（4-（3-（2-氟丙-2-基）-1,2,4-恶二唑-5-基 ）哌啶-1-基）嘧啶-4-基氨基）-N，N-二甲基苯甲酰胺; - 氟-4-（5-氟-6-（4-（3-（2-氟 - 丙-2-基）-1,2,4-恶二唑-5-基）哌啶-1-基） 吡啶-4-基氨基）-N-甲基苯甲酰胺; 和3-氟-4-（5-氟-6-（4-（3-（2-氟丙-2-基）-1,2,4-恶二唑-5-基）哌啶-1-基） 4-氨基）苯甲酰胺及其药学上可接受的盐，溶剂合物和水合物，其可用作单一药剂或与一种或多种另外的药剂如DPP-IV抑制剂，双胍类，α 葡萄糖苷酶抑制剂，胰岛素类似物，磺酰脲类，SGLT2抑制剂，氯噻嗪，噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如选自以下的病症：GPR119-受体相关病症; 通过增加肠降血糖素的分泌而改善的状况; 通过增加血液肠降血糖水平来改善病情; 以低骨量为特征的病症; 神经障碍 代谢相关疾病; 2型糖尿病; 肥胖; 和相关的并发症。

公开(公告)号：US07776891B2

公开(公告)日：2010-08-17

申请号：US11659608

申请日：2005-08-12

Applicant: Weichao Chen ,  Alec D. Lebsack ,  Benito Munoz ,  Shankar Venkatraman ,  Bowei Wang

Inventor： Weichao Chen ,  Alec D. Lebsack ,  Benito Munoz ,  Shankar Venkatraman ,  Bowei Wang

IPC: A61K31/44 ,  C07D401/02

CPC classification number: C07K5/06139 ,  C07K5/06191

Abstract: Compounds of Formula (I) are antagonists of VLA-4, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of inflammatory bowel disease including ulcerative colitis and Crohn's disease, multiple sclerosis, asthma, and rheumatoid arthritis.

Abstract translation: 式（I）化合物是VLA-4的拮抗剂，因此可用于抑制或预防细胞粘附和细胞粘附介导的病理学。 这些化合物可以配制成药物组合物，并且适用于治疗包括溃疡性结肠炎和克罗恩病，多发性硬化，哮喘和类风湿性关节炎的炎性肠病。