4-(2-{(2R)-2-[(1E,3S)-3-hydroxy-4-(3-methylphenyl)but-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)benzoic acid | 494223-72-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(2-{(2R)-2-[(1E,3S)-3-hydroxy-4-(3-methylphenyl)but-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)benzoic acid
• 英文别名: (15α,13E)-1,6-(1,4-interphenylene)-9-oxo-15-hydroxy-16-(3-methylphenyl)-2,3,4,5,17,18,19,20-octanor-8-azaprost-13-enoic acid；4-[2-[(2R)-2-[(E,3S)-3-hydroxy-4-(3-methylphenyl)but-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid
• CAS: 494223-72-2
• 化学式: C₂₄H₂₇NO₄
• 分子量: 393.483
• InChiKey: GGVGHMDLZIWZOR-JEUBMUGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl (4R,5E,7S)-4-amino-7-hydroxy-8-(3-methylphenyl)-5-octenoate hydrochloride 在 咪唑 、 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 4-(2-{(2R)-2-[(1E,3S)-3-hydroxy-4-(3-methylphenyl)but-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)benzoic acid
  参考文献：
  名称：

  Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists

  摘要：

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.018

文献信息

• Gamma lactams as prostaglandin agonists and use thereof
  申请人：Araldi Luca Gian

  公开号：US20050288357A1

  公开（公告）日：2005-12-29

  1,2-substituted 5-pyrrolidinone compounds are provided, and methods of treatment and pharmaceutical composition that utilize or comprise one or more such compounds. Compounds of the invention are useful for a variety of therapies, including treating or preventing preterm labor, dysmenorrhea, asthma, hypertension, infertility or fertility disorder, undesired blood clotting, preeclampsia or eclampsia, an eosinophil disorder, sexual dysfunction, osteporosis and other destructive bone disease or disorder, renal dysfunction, an immune deficiency disorder, dry eye, ichthyosis, elevated intraocular pressure, sleep disorder, or gastric ulcer, inflammatory disorders and other diseases and disorders associated with the prostaglandin family of compounds.

  本发明提供了1,2-取代的5-吡咯烷酮化合物，并提供了利用或包含一个或多个此类化合物的治疗方法和制药组合物。本发明的化合物可用于各种治疗方案，包括治疗或预防早产、痛经、哮喘、高血压、不孕或生育障碍、不良血液凝固、先兆子痫或子痫、嗜酸性粒细胞异常、性功能障碍、骨质疏松和其他骨骼疾病或障碍、肾功能障碍、免疫缺陷性疾病、干眼症、鱼鳞病、眼内压升高、睡眠障碍或胃溃疡、炎症性疾病和其他与前列腺素类化合物有关的疾病和障碍。
• 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。
• 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）。
• US7419999B2
  申请人：——

  公开号：US7419999B2

  公开（公告）日：2008-09-02
• US7608637B2
  申请人：——

  公开号：US7608637B2

  公开（公告）日：2009-10-27