2-([2-((2R)-2-((1E,3S)-4-[3-(1-benzofuran-2-yl)phenyl]-3-hydroxybut-1-enyl)-5-oxopyrrolidin-1-yl)ethyl]sulfanyl)-1,3-thiazole-4-carboxylic acid | 494223-92-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: 2-([2-((2R)-2-((1E,3S)-4-[3-(1-benzofuran-2-yl)phenyl]-3-hydroxybut-1-enyl)-5-oxopyrrolidin-1-yl)ethyl]sulfanyl)-1,3-thiazole-4-carboxylic acid
• 英文别名: 2-{[2-((2R)-2-{(1E,3S)-4-[3-(1-benzofuran-2-yl)phenyl]-3-hydroxybut-1-enyl}-5-oxopyrrolidin-1-yl)ethyl]sulfanyl}-1,3-thiazol-4-carboxylic acid；2-[2-[(2R)-2-[(E,3S)-4-[3-(1-benzofuran-2-yl)phenyl]-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid
• CAS: 494223-92-6
• 化学式: C₂₈H₂₆N₂O₅S₂
• 分子量: 534.657
• InChiKey: PWCLBJYOGZNYIQ-PCBIHFGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  157
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-羟基苯乙酸 在 吡啶 、 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 正丁基锂 、 硼烷四氢呋喃络合物 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 mineral oil 为溶剂， 反应 51.91h， 生成 2-([2-((2R)-2-((1E,3S)-4-[3-(1-benzofuran-2-yl)phenyl]-3-hydroxybut-1-enyl)-5-oxopyrrolidin-1-yl)ethyl]sulfanyl)-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists

  摘要：

  To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl omega-chain moiety of the gamma-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.008

文献信息

• PHARMACEUTICAL COMPOSITION FOR TREATMENT OF DISEASES ASSOCIATED WITH DECREASE IN BONE MASS COMPRISING EP4 AGONIST AS ACTIVE INGREDIENT
  申请人：MARUYAMA Toru

  公开号：US20100010222A1

  公开（公告）日：2010-01-14

  A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP 4 agonist as an active ingredient. An EP 4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).

  一种用于局部治疗预防和/或治疗与骨量减少相关疾病的药物组合物，包括EP4激动剂作为活性成分。EP4激动剂，其中包括具有前列腺素骨架的化合物作为代表，具有促进骨形成的作用，因此对于预防和/或治疗与骨量减少相关的疾病（如原发性骨质疏松症、继发性骨质疏松症、骨癌转移、高钙血症、帕吉特病、骨丢失和骨坏死、术后骨生成、骨移植替代疗法）非常有用。
• PREVENTIVE AND/OR REMEDY FOR LOWER URINARY TRACT DISEASES CONTAINING EP4 AGONIST
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1782830A1

  公开（公告）日：2007-05-09

  A preventive and/or a remedy for lower urinary tract diseases such as inflammation in the lower urinary tract, cystitis (interstitial cystitis, etc.) and urethritis; (2) an agent for improving bladder compliance and/or bladder capacity; and (3) an agent for protecting bladder mucosa and/or bladder epithelial cells and/or promoting the regeneration thereof; each containing an EP4 agonist. An EP4 agonist is useful in ameliorating symptoms of lower urinary tract diseases such as (1) frequent urination, (2) urgency of urination, (3) pain in the reproductive organs and/or lower urinary tract (for example, bladder pain, urinary tract pain, vulvar pain, vaginal pain, scrotal pain, perineal pain, pelvic pain, etc.) and/or (4) discomfort in the reproductive organs and/or lower urinary tract. Among all, a selective EP4 agonist is useful as a preventive and/or remedy for lower urinary tract diseases having no side effect.

  一种预防和/或治疗下尿路疾病，如下尿路炎症、膀胱炎（间质性膀胱炎等）和尿道炎的制剂；(2) 一种改善膀胱顺应性和/或膀胱容量的制剂；(3) 一种保护膀胱粘膜和/或膀胱上皮细胞和/或促进其再生的制剂；每种制剂都含有一种EP4激动剂。 EP4 激动剂可用于改善下尿路疾病的症状，如(1) 尿频，(2) 尿急，(3) 生殖器官和/或下尿路疼痛（例如，膀胱痛、尿道痛、外阴痛、阴道痛、阴囊痛、会阴痛、骨盆痛等）和/或(4) 生殖器官和/或下尿路不适。其中，选择性 EP4 激动剂可用于预防和/或治疗下尿路疾病，且无副作用。
• PREVENTIVE AND/OR REMEDY FOR HYPERKALEMIA CONTAINING EP4 AGONIST
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1782829A1

  公开（公告）日：2007-05-09

  The present invention relates to a preventive and/or therapeutic agent for hyperkalemia, and a potassium excretion promoter containing EP4 agonist. Since EP4 agonist promotes potassium excretion, it is useful as a preventive and/or therapeutic agent for hyperkalemia. In addition, if selective EP4 agonist uses, it is a preventive and/or therapeutic agent for hyperkalemia without side effects. Further, if EP4 agonist is used, it is useful as improving agent for various symptoms (e.g. paresthesia, error of perception, weakness, myoparalysis, nausea, vomit, abdominal pain, diarrhea, arrhythmia, atrioventricular block, ventricular fibrillation, atrial fibrillation, cardiac arrest, asphyxia and/or dyspnoea etc.).

  本发明涉及一种高钾血症的预防和/或治疗剂，以及一种含有 EP4 激动剂的钾排泄促进剂。由于 EP4 激动剂能促进钾排泄，因此可用作高钾血症的预防和/或治疗剂。此外，如果使用选择性 EP4 激动剂，它是一种无副作用的高钾血症预防和/或治疗剂。此外，如果使用 EP4 激动剂，还可作为改善各种症状（如麻痹、知觉错误、虚弱、肌麻痹、恶心、呕吐、腹痛、腹泻、心律失常、房室传导阻滞、心室颤动、心房颤动、心脏骤停、窒息和/或呼吸困难等）的药物。
• Pharmaceutical composition for treatment of diseases associated with decrease in bone mass comprising EP4 agonist as active ingredient
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：EP2255829A2

  公开（公告）日：2010-12-01

  A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EP4 agonist as an active ingredient. An EP4 agonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).

  一种局部用药的药物组合物，用于预防和/或治疗与骨量减少有关的疾病，其活性成分包括一种 EP4 激动剂。EP4激动剂（其中包括以前列腺素骨架为代表的化合物）具有促进骨形成的作用，因此可用于预防和/或治疗与骨量减少有关的疾病（骨病，如原发性骨质疏松症、继发性骨质疏松症、癌症骨转移、高钙血症、Paget病、骨丢失和骨坏死、术后成骨、植骨替代疗法）。
• Preventive And/Or Remedy For Lower Urinary Tract Diseases Containing Ep4 Agonist
  申请人：Okada Hiroki

  公开号：US20080021021A1

  公开（公告）日：2008-01-24

  (1) A preventive and/or a remedy for lower urinary tract diseases such as inflammation in the lower urinary tract, cystitis (interstitial cystitis, etc.) and urethritis; (2) an agent for improving bladder compliance and/or bladder capacity; and (3) an agent for protecting bladder mucosa and/or bladder epithelial cells and/or promoting the regeneration thereof; each containing an EP 4 agonist. An EP 4 agonist is useful in ameliorating symptoms of lower urinary tract diseases such as (1) frequent urination, (2) urgency of urination, (3) pain in the reproductive organs and/or lower urinary tract (for example, bladder pain, urinary tract pain, vulvar pain, vaginal pain, scrotal pain, perineal pain, pelvic pain, etc.) and/or (4) discomfort in the reproductive organs and/or lower urinary tract. Among all, a selective EP 4 agonist is useful as a preventive and/or remedy for lower urinary tract diseases having no side effect.

  (1) 可用于预防和/或治疗下尿路疾病，例如下尿路炎症、膀胱炎（间质性膀胱炎等）和尿道炎；(2) 可用于改善膀胱顺应性和/或膀胱容量；以及 (3) 可用于保护膀胱黏膜和/或膀胱上皮细胞和/或促进其再生； 以上用途均包含一种EP4受体激动剂。 EP4受体激动剂在缓解以下症状方面是有用的：(1) 尿频；(2) 急性尿意；(3) 生殖器官和/或下尿路的疼痛（例如膀胱痛、尿路痛、外阴痛、阴道痛、睾丸痛、会阴痛、盆腔痛等）；以及 (4) 生殖器官和/或下尿路的不适。其中，选择性EP4激动剂作为预防和/或治疗下尿路疾病的药物，具有无副作用的优势。