[(2R)-1-oxo-1-pyrrolidin-1-ylpropan-2-yl] 2-bromo-2-phenylacetate | 449779-55-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: [(2R)-1-oxo-1-pyrrolidin-1-ylpropan-2-yl] 2-bromo-2-phenylacetate
• CAS: 449779-55-9
• 化学式: C₁₅H₁₈BrNO₃
• 分子量: 340.217
• InChiKey: PUNONWSSVWYRGI-JTDNENJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(2R)-1-oxo-1-pyrrolidin-1-ylpropan-2-yl] 2-bromo-2-phenylacetate 在 过氧化氢,锂盐(1:1) 、 lithium tert-butoxide 作用下， 以 四氢呋喃 为溶剂， 生成 (R)-(5,7-Dipropyl-3-trifluoromethyl-benzo[d]isoxazol-6-yloxy)-phenyl-acetic acid
  参考文献：
  名称：

  O-Arylmandelic acids as highly selective human PPAR α/γ agonists

  摘要：

  A new class of O-arylmandelic acid PPAR agonists show excellent anti-hyperglycemic efficacy in a db/db mouse model of DM2. These PPARalpha-weighted agonists do not show the typical PPARgamma associated side effects of BAT proliferation and cardiac hypertrophy in a rat tolerability assay. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00702-9
• 作为产物：
  描述：

  (9CI)-1-[(2R)-2-羟基-1-氧代丙基]-吡咯烷 在 sodium tetrahydroborate 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(2R)-1-oxo-1-pyrrolidin-1-ylpropan-2-yl] 2-bromo-2-phenylacetate
  参考文献：
  名称：

  Design and Synthesis of α-Aryloxyphenylacetic Acid Derivatives:  A Novel Class of PPARα/γ Dual Agonists with Potent Antihyperglycemic and Lipid Modulating Activity

  摘要：

  The synthesis and structure-activity relationships of novel series of alpha-aryloxyphenylacetic acids as PPARalpha/gamma dual agonists are reported. The initial search for surrogates of the ester group in the screen lead led first to the optimization of a subseries with a ketone moiety. Further efforts to modify the ketone subseries led to the design and synthesis of two new subseries containing fused heterocyclic ring systems. All these analogues were characterized by their "super" PPARalpha agonist activity and weak or partial agonist activity on PPARgamma in PPAR-GAL4 transactivation assays despite their similar binding affinities for both receptors. The cocrystal structures of compounds 7 and rosiglitazone with PPARgamma-LBD were compared, and significant differences were found in their interactions with the receptor. Select analogues in each subseries were further evaluated for in vivo efficacy. They all showed excellent anti-hyperglycemic efficacy in a db/db mouse model and hypolipidemic activity in hamster and dog models without provoking the typical PPARgamma-associated side effects in the rat tolerability assay.

  DOI：

  10.1021/jm0502135

文献信息

• US7495020B2
  申请人：——

  公开号：US7495020B2

  公开（公告）日：2009-02-24