(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-hydroxyethyl)-1,3-oxazolidin-2-one | 729611-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-hydroxyethyl)-1,3-oxazolidin-2-one
• 英文别名: (4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-hydroxyethyl)-1,3-oxazalidin-2-one；(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-hydroxyethyl)-1,3-oxazolidine-2-one；(4R)-4-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-(2-hydroxyethyl)-1,3-oxazolidin-2-one
• CAS: 729611-28-3
• 化学式: C₁₂H₂₅NO₄Si
• 分子量: 275.42
• InChiKey: MLGMMIPYGIPVKH-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-hydroxyethyl)-1,3-oxazolidin-2-one 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 S-{2-[(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-oxo-1,3-oxazolidin-3-yl]ethyl}ethanethioate
  参考文献：
  名称：

  Synthesis and evaluation of a potent, well-balanced EP 2 /EP 3 dual agonist

  摘要：

  A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (> 2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.035
• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 水 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 (4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-hydroxyethyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  EP1707208

  摘要：

  公开号：

文献信息

• Discovery of highly potent dual EP 2 and EP 3 agonists with subtype selectivity
  作者：Akihiro Kinoshita、Masato Higashino、Yoshiyuki Aratani、Akito Kakuuchi、Hidekazu Matsuya、Kazuyuki Ohmoto

  DOI：10.1016/j.bmcl.2015.12.039

  日期：2016.2

  The cyclic carbamate derivatives, 2-[2-((4S)-4-(1E,3R)-8-fluoro-3-hydroxy-4,4-dimethyl-1-octenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (5) and 2-[2-((4S)-4-(1E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxy-1-propenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (7) were identified as the first potent dual EP2 and EP3 agonists with selectivity against the EP1 and EP4 subtypes. Compounds 5 and 7 demonstrated highly potent dual EP2 and EP3 agonist activity with EC50 values of 10 nM or less. In addition, these compounds possess structural features distinct from natural prostaglandins, such as a cyclic carbamate moiety, a dimethyl or cyclobutyl group and a terminal fluorine atom. (C) 2015 Elsevier Ltd. All rights reserved.
• 8-AZAPROSTAGLANDIN DERIVATIVES AND MEDICINAL USES THEREOF
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1586564B1

  公开（公告）日：2012-11-28