4R-(1S,2-dimethylpropyl)dihydrofuran-2-one | 850080-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 4R-(1S,2-dimethylpropyl)dihydrofuran-2-one
• 英文别名: (4R)-4-[(2S)-3-methylbutan-2-yl]oxolan-2-one
• CAS: 850080-21-6
• 化学式: C₉H₁₆O₂
• 分子量: 156.225
• InChiKey: KJMKPUVCLLUEQO-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4R-(1S,2-dimethylpropyl)dihydrofuran-2-one 在 镍 sodium azide 、 氢溴酸 、 氢气 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 20.0~60.0 ℃ 、330.95 kPa 条件下， 反应 22.0h， 生成 4R-(1S,2-dimethylpropyl)pyrrolidin-2-one
  参考文献：
  名称：

  Structure−Activity Relationships of Pregabalin and Analogues That Target the α₂-δ Protein

  摘要：

  Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [H-3]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [H-3]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.

  DOI：

  10.1021/jm049762l
• 作为产物：
  描述：

  (3R,4S)-3-Hydroxymethyl-4,5-dimethyl-hexanoic Acid Tert-butyl Ester 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以1.4 g的产率得到4R-(1S,2-dimethylpropyl)dihydrofuran-2-one
  参考文献：
  名称：

  Structure−Activity Relationships of Pregabalin and Analogues That Target the α₂-δ Protein

  摘要：

  Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [H-3]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [H-3]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.

  DOI：

  10.1021/jm049762l

文献信息

• [EN] ALPHA 2 DELTA LIGANDS TO TREAT TINNITUS<br/>[FR] LIGANDS ALPHA 2 DELTA DANS LE TRAITEMENT DES ACOUPHENES
  申请人：WARNER LAMBERT CO

  公开号：WO2003063845A1

  公开（公告）日：2003-08-07

  The invention relates to a method of treating tinnitus by administering an alpha2delta ligand such as, for example, a compound of Formula (I) and pharmaceutically acceptable salts thereof, wherein R1 is hydrogen or straight or branched lower alkyl, and n is an integer of from 4 to 6.
• Structure−Activity Relationships of Pregabalin and Analogues That Target the α₂-δ Protein
  作者：Thomas R. Belliotti、Thomas Capiris、I. Victor Ekhato、Jack J. Kinsora、Mark J. Field、Thomas G. Heffner、Leonard T. Meltzer、Jacob B. Schwarz、Charles P. Taylor、Andrew J. Thorpe、Mark G. Vartanian、Lawrence D. Wise、Ti Zhi-Su、Mark L. Weber、David J. Wustrow

  DOI：10.1021/jm049762l

  日期：2005.4.1

  Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [H-3]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [H-3]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.