(R)-methyl 4-(2-(2-formyl-5-oxopyrrolidin-1-yl)ethyl)benzoate | 635309-85-2

• 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: (R)-methyl 4-(2-(2-formyl-5-oxopyrrolidin-1-yl)ethyl)benzoate
• 英文别名: methyl 4-[2-[(2R)-2-formyl-5-oxopyrrolidin-1-yl]ethyl]benzoate
• CAS: 635309-85-2
• 化学式: C₁₅H₁₇NO₄
• 分子量: 275.304
• InChiKey: VHMDROQTDMADNL-CYBMUJFWSA-N

物化性质

• 沸点：
  475.8±45.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-methyl 4-(2-(2-formyl-5-oxopyrrolidin-1-yl)ethyl)benzoate 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 4-(2-((S)-2-((S)-5-cyclobutyl-3-hydroxypentyl)-5-oxopyrrolidin-1-yl)ethyl)benzoic acid
  参考文献：
  名称：

  Lactams as EP₄ Prostanoid Receptor Agonists. 3. Discovery of N-Ethylbenzoic Acid 2-Pyrrolidinones as Subtype Selective Agents

  摘要：

  Two distinct synthetic schemes were applied to access heteroatom-containing alpha-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP4 receptor activity. gamma-Lactams were characterized for their prostanoid EP receptor affinities and EP4 activity and found to be selective for the EP2 and EP4 receptors or selective for the EP4 subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.

  DOI：

  10.1021/jm049290a
• 作为产物：
  描述：

  (5S)-5-[(benzyloxy)methyl]dihydrofuran-2(3H)-one 在 palladium on activated charcoal 1,5-二氮杂双环[4.3.0]壬-5-烯 、 potassium tert-butylate 、 氢气 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 8.2h， 生成 (R)-methyl 4-(2-(2-formyl-5-oxopyrrolidin-1-yl)ethyl)benzoate
  参考文献：
  名称：

  Lactams as EP₄ Prostanoid Receptor Agonists. 3. Discovery of N-Ethylbenzoic Acid 2-Pyrrolidinones as Subtype Selective Agents

  摘要：

  Two distinct synthetic schemes were applied to access heteroatom-containing alpha-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP4 receptor activity. gamma-Lactams were characterized for their prostanoid EP receptor affinities and EP4 activity and found to be selective for the EP2 and EP4 receptors or selective for the EP4 subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.

  DOI：

  10.1021/jm049290a

文献信息

• [EN] LACTAM COMPOUNDS AS EP4 RECEPTOR-SELECTIVE AGONISTS FOR USE IN THE TREATMENT OF EP4-MEDIATED DISEASES AND CONDITIONS<br/>[FR] COMPOSÉS LACTAMES EN TANT QU'AGONISTES SÉLECTIFS DU RÉCEPTEUR EP4 POUR L'UTILISATION DANS LE TRAITEMENT DE MALADIES ET D'ÉTATS À MÉDIATION PAR EP4
  申请人：CAYMAN CHEMICAL CO INC

  公开号：WO2014144610A1

  公开（公告）日：2014-09-18

  Disclosed herein are compounds of formula (I) wherein L1, L2, L3, R1, R4, R5, and R6 are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, osteoporosis, bone fracture, periodontal bone loss, orthopedic implant, alopecia, neuropathic pain, and related disorders. Pharmaceutical compositions and methods of treating conditions or disorders are also described.

  披露了公式(I)的化合物，其中L1、L2、L3、R1、R4、R5和R6如说明书定义。公式(I)的化合物是EP4激动剂，可用于治疗青光眼、骨质疏松症、骨折、牙周骨丢失、骨科植入物、脱发、神经性疼痛及相关疾病。还描述了药物组合物和治疗条件或疾病的方法。
• LACTAM COMPOUNDS AS EP4 RECEPTOR-SELECTIVE AGONISTS FOR USE IN THE TREATMENT OF EP4-MEDIATED DISEASES AND CONDITIONS
  申请人：CAYMAN CHEMICAL COMPANY, INC.

  公开号：US20160060216A1

  公开（公告）日：2016-03-03

  Disclosed herein are compounds of formula (I) wherein L 1 , L 2 , L 3 , L 4 , R 1 , R 4 , R 5 , R 6 , and s are as defined in the specification. Compounds of formula (I) are EP 4 agonists useful in the treatment of glaucoma, osteoporosis, bone fracture, periodontal bone loss, orthopedic implant, alopecia, neuropathic pain, and related disorders. Pharmaceutical compositions and methods of treating conditions or disorders are also described.

  披露了公式(I)的化合物 其中L 1 , L 2 , L 3 , L 4 , R 1 , R 4 , R 5 , R 6 ，和s如说明书所定义。 公式(I)的化合物是EP 4 激动剂，用于治疗青光眼、骨质疏松症、骨折、牙周骨丢失、矫形植入物、脱发、神经性疼痛和相关的疾病。 还描述了药物组合物和治疗条件或疾病的方法。
• Discovery of novel prostaglandin analogs of PGE2 as potent and selective EP2 and EP4 receptor agonists
  作者：Yufang Xiao、Gian Luca Araldi、Zhong Zhao、Nadia Brugger、Srinivasa Karra、David Fischer、Elizabeth Palmer

  DOI：10.1016/j.bmcl.2007.05.025

  日期：2007.8

  introduction of diene groups at the omega-side chain have been synthesized and evaluated for their binding affinity for EP(2) and EP(4) receptors. An optimized analog (compound 9b) showed high potency and selectivity for the EP(4) receptor over other known receptors.

  已经合成了在欧米茄侧链上引入二烯基的PGE（2）类似物，并评估了它们对EP（2）和EP（4）受体的结合亲和力。一种优化的类似物（化合物9b）对EP（4）受体显示出比其他已知受体更高的效价和选择性。
• G-lactam derivatives as prostaglandin agonists
  申请人：Araldi Luca Gian

  公开号：US20060194865A1

  公开（公告）日：2006-08-31

  The present invention relates γ-lactam derivatives, in particular for use as medicaments, as well as pharmaceutical formulations containing such γ-lactam derivatives. Said γ-lactam derivatives are useful in the treatment and/or prevention of asthma, hypertension, osteoporosis, sexual dysfunction and fertility disorders.

  本发明涉及γ-内酰胺衍生物，特别是用作药物，以及含有这种γ-内酰胺衍生物的制药配方。所述γ-内酰胺衍生物在哮喘、高血压、骨质疏松症、性功能障碍和生育障碍的治疗和/或预防中有用。
• METHODS, SYSTEMS, AND COMPOSITIONS FOR PROMOTING BONE GROWTH
  申请人：CAYMAN CHEMICAL COMPANY, INC.

  公开号：US20160158413A1

  公开（公告）日：2016-06-09

  The present invention relates to novel bone compositions for locally delivering a therapeutic agent to the site of a bone defect. Therapeutic agents may promote repair of the bone defect and/or treat conditions or disorders such as pain, inflammation, cancer, and infection. The compositions include calcium phosphate cements and a demineralized bone matrix or a collagen sponge. The compositions are useful for implantation in a patient at the site of a bone defect.

  本发明涉及一种新型骨组成物，用于局部向骨缺损部位提供治疗剂。治疗剂可以促进骨缺损的修复和/或治疗疼痛、炎症、癌症和感染等病症或疾病。该组成物包括磷酸钙水泥和脱矿骨基质或胶原海绵。该组成物可用于患者的骨缺损部位植入。