雷利帕格 | 1187856-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 雷利帕格
• 英文名称: Ralinepag
• 英文别名: 2-[[4-[[(4-chlorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid
• CAS: 1187856-49-0
• 化学式: C₂₃H₂₆ClNO₅
• 分子量: 431.9
• InChiKey: NPDKXVKJRHPDQT-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：15mg/mL； DMF:PBS (pH 7.2) (1:8)：0.11mg/mL；二甲基亚砜：10mg/mL；乙醇：10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为产物：
  描述：

  tert-butyl 2-(((1r,4r)-4-(((4-chlorophenyl)-(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetate 以98的产率得到雷利帕格
  参考文献：
  名称：

  J. Med. Chem. 2017, 60, 913-927

  摘要：

  DOI：

文献信息

• [EN] MODULATORS OF THE PROSTACYCLIN (PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR DE LA PROSTACYCLINE (PGI2) UTILES POUR LE TRAITEMENT DE TROUBLES LIÉS À CELUI-CI
  申请人：ARENA PHARM INC

  公开号：WO2009117095A1

  公开（公告）日：2009-09-24

  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).

  本发明涉及式（XIIIa）的酰胺衍生物及其药物组合物，其调节PGI2受体的活性。本发明的化合物和药物组合物适用于治疗以下疾病的方法：肺动脉高压（PAH）；特发性PAH；家族性PAH；与胶原血管疾病、先天性心脏病、门脉高压、HIV感染、药物或毒素摄入、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）或肺毛细血管血管瘤病（PCH）相关的PAH；具有明显静脉或毛细血管受累的PAH；血小板聚集；冠状动脉疾病；心肌梗死；短暂性缺血发作；心绞痛；中风；缺血再灌注损伤；再狭窄；心房颤动；血栓形成在介入治疗或冠状动脉旁路手术个体中或患有心房颤动的个体中；动脉粥样硬化；动脉血栓形成；哮喘或其症状；糖尿病相关疾病，如糖尿病周围神经病变、糖尿病肾病或糖尿病视网膜病变；青光眼或眼内压异常的其他眼部疾病；高血压；炎症；牛皮癣；银屑病性关节炎；类风湿性关节炎；克罗恩病；移植排斥反应；多发性硬化；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；痤疮；1型糖尿病；2型糖尿病；败血症；慢性阻塞性肺疾病（COPD）。
• [EN] CRYSTALLINE FORMS AND PROCESSES FOR THE PREPARATION OF PGI2 RECEPTOR AGONISTS<br/>[FR] FORMES CRISTALLINES ET PROCÉDÉS POUR LA PRÉPARATION D'AGONISTES DU RÉCEPTEUR PGI2
  申请人：ARENA PHARM INC

  公开号：WO2011037613A1

  公开（公告）日：2011-03-31

  The present invention relates to salts of 2-(2-((4-(((4-chlorophenyl)(phenyl)-carbamoyloxy)methyl)cyclohexyl)methoxy)acetamido)ethanesulfonic acid (Compound 1) and crystalline forms, solvates and hydrates thereof. The present invention further relates to processes and intermediates useful in the preparation of Compound I and salts, solvates and hydrates thereof. Crystalline forms, salts, solvates and hydrates of the present invention and pharmaceutical compositions thereof are useful in the treatment of, for example, pulmonary arterial hypertension (PAH); platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder; 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; atherosclerosis; acne; type I diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

  本发明涉及2-(2-((4-(((4-氯苯基)(苯基)-氨甲酰氧基)甲基)环己基)甲氧基)乙酰胺基)乙磺酸盐（化合物1）及其结晶形式、溶剂合物和水合物。本发明还涉及用于制备化合物I及其盐、溶剂合物和水合物的有用过程和中间体。本发明的结晶形式、盐、溶剂合物和水合物以及其药物组合物在治疗例如肺动脉高压（PAH）；血小板聚集；冠状动脉疾病；心肌梗死；短暂性缺血发作；心绞痛；中风；缺血再灌注损伤；再狭窄；心房颤动；血栓形成；动脉粥样硬化血栓形成；哮喘或其症状；糖尿病相关疾病；青光眼或其他眼部异常眼压疾病；高血压；炎症；牛皮癣；银屑病性关节炎；类风湿关节炎；克罗恩病；移植排斥反应；多发性硬化；系统性红斑狼疮（SLE）；溃疡性结肠炎；动脉粥样硬化；痤疮；1型糖尿病；2型糖尿病；败血症；和慢性阻塞性肺病（COPD）等方面有用。
• MODULATORS OF THE PROSTACYCLIN (PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Tran Thuy-Anh

  公开号：US20110053958A1

  公开（公告）日：2011-03-03

  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).

  本发明涉及式（XIIIa）的酰胺衍生物及其药物组合物，其调节PGI2受体的活性。本发明的化合物和药物组合物针对以下治疗方法有用：肺动脉高压（PAH）；特发性PAH；家族性PAH；与胶原血管病、先天性心脏病、门静脉高压、HIV感染、药物或毒素摄入、遗传性出血性毛细血管扩张症、脾切除、肺静脉闭塞病（PVOD）或肺毛细血管瘤病（PCH）相关的PAH；有显著静脉或毛细血管参与的PAH；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；中风；缺血再灌注损伤；再狭窄；心房颤动；血栓形成在冠状动脉成形术或冠状动脉搭桥手术个体中或在患有心房颤动的个体中；动脉粥样硬化；动脉粥样硬化性血栓形成；哮喘或其症状；糖尿病相关疾病，如糖尿病性周围神经病、糖尿病性肾病或糖尿病性视网膜病变；青光眼或其他眼部异常内压疾病；高血压；炎症；银屑病；银屑病性关节炎；类风湿性关节炎；克罗恩病；移植排斥；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；痤疮；1型糖尿病；2型糖尿病；败血症；慢性阻塞性肺疾病（COPD）。
• Modulators of the prostacyclin (PGI2) receptor useful for the treatment of disorders related thereto
  申请人：Arena Pharmaceuticals, Inc.

  公开号：US10668033B2

  公开（公告）日：2020-06-02

  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).

  本发明涉及可调节 PGI2 受体活性的式 (XIIIa) 酰胺衍生物及其药物组合物。本发明的化合物及其药物组合物用于治疗以下疾病的方法：肺动脉高压 (PAH)；特发性 PAH；家族性 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) 或肺毛细血管血管瘤病 (PCH) 相关的 PAH；严重累及静脉或毛细血管的 PAH；血小板聚集；冠状动脉疾病；心肌梗塞；短暂性脑缺血发作、心绞痛；中风；缺血再灌注损伤；再狭窄；心房颤动；血管成形术或冠状动脉搭桥术患者或心房颤动患者血栓形成；动脉粥样硬化；动脉粥样硬化性血栓形成；哮喘或其症状；糖尿病相关疾病，如糖尿病周围神经病变、糖尿病肾病或糖尿病视网膜病变；青光眼或其他眼内压异常的眼部疾病；高血压；炎症；银屑病；银屑病关节炎；类风湿性关节炎、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、血管再狭窄、动脉粥样硬化、痤疮、1 型糖尿病、2 型糖尿病、败血症和慢性阻塞性肺病 (COPD)。
• Method of treating conditions related to the PGI2 receptor
  申请人：Arena Pharmaceuticals, Inc.

  公开号：US10688076B2

  公开（公告）日：2020-06-23

  Provided in some embodiments are titration packages, kits, and methods of treating pulmonary arterial hypertension comprising prescribing and/or administering to a patient in need thereof 2-(((1r,4r)-4-(((4-chlorophenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, via a titration scheme that comprises the up-titration of Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, over a period of no more than about nine weeks until an optimized dose is administered.

  在一些实施方案中，提供了治疗肺动脉高压的滴定包、试剂盒和方法，包括向有需要的患者处方和/或给药2-(((1r,4r)-4-(((4-氯苯基)(苯基)氨基甲酰氧基)甲基)环己基)甲氧基)乙酸(化合物1)、或其药学上可接受的盐、水合物或溶液，通过滴定方案将化合物 1 或其药学上可接受的盐、水合物或溶液向上滴定，滴定时间不超过约九周，直至给药达到最佳剂量。