(4S,5R)-3-benzyl-5-cyclohexyl-4-(hydroxymethyl)oxazolidin-2-one | 1280013-85-5

• 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: (4S,5R)-3-benzyl-5-cyclohexyl-4-(hydroxymethyl)oxazolidin-2-one
• CAS: 1280013-85-5
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: KJPVWKKBYVVLHM-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  49.77
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (4S,5R)-3-benzyl-5-cyclohexyl-4-(hydroxymethyl)oxazolidin-2-one 在 盐酸 、 Jones reagent 、 20 % Pd(OH)2/C 、 氢气 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 、 乙醇 、 水 、 丙酮 为溶剂， 生成
  参考文献：
  名称：

  Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate

  摘要：

  Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.109
• 作为产物：
  描述：

  3-cyclohexylacrylic acid 在 titanium(IV) isopropylate 、 D-(-)-酒石酸二乙酯 、 过氧化氢异丙苯 、 硫酸 、 sodium hydride 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (4S,5R)-3-benzyl-5-cyclohexyl-4-(hydroxymethyl)oxazolidin-2-one
  参考文献：
  名称：

  Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate

  摘要：

  Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.109

文献信息

• Directed openings of 2,3-epoxy alcohols via reactions with isocyanates: synthesis of (+)-erythro-dihydrosphingosine
  作者：William R. Roush、Michael A. Adam

  DOI：10.1021/jo00220a015

  日期：1985.10
• Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: A highly potent orally available CCR5 selective antagonist
  作者：Rena Nishizawa、Toshihiko Nishiyama、Katsuya Hisaichi、Chiaki Minamoto、Masayuki Murota、Yoshikazu Takaoka、Hisao Nakai、Hideaki Tada、Kenji Sagawa、Shiro Shibayama、Daikichi Fukushima、Kenji Maeda、Hiroaki Mitsuya

  DOI：10.1016/j.bmc.2011.05.022

  日期：2011.7

  Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. (C) 2011 Elsevier Ltd. All rights reserved.