dimethyl {3-[3-(2-naphthyl)phenyl]-2-oxopropyl}phosphonate | 1365178-22-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: dimethyl {3-[3-(2-naphthyl)phenyl]-2-oxopropyl}phosphonate
• CAS: 1365178-22-8
• 化学式: C₂₁H₂₁O₄P
• 分子量: 368.369
• InChiKey: MMPYRIHAQREVHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  dimethyl {3-[3-(2-naphthyl)phenyl]-2-oxopropyl}phosphonate 在 硼烷四氢呋喃络合物 、 sodium hydride 、 sodium hydroxide 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 甲苯 、 mineral oil 为溶剂， 反应 4.92h， 生成 2-{[2-((2R)-2-{(1E,3S)-3-hydroxy-4-[3-(2-naphthyl)phenyl]but-1-enyl}-5-oxopyrrolidin-1-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic 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
• 作为产物：
  描述：

  2-(3-bromophenyl)-N-methoxy-N-methylacetamide 在 正丁基锂 、 palladium diacetate 、 sodium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 乙二醇二甲醚 、 正己烷 、 甲苯 为溶剂， 反应 15.0h， 生成 dimethyl {3-[3-(2-naphthyl)phenyl]-2-oxopropyl}phosphonate
  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

• Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.04.008

  日期：2012.6

  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.