4(S)-(1-methylethyl)-3-(1-oxo-3-(2-thienyl)propyl)-2-oxazolidinone | 138296-00-1

• 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: 4(S)-(1-methylethyl)-3-(1-oxo-3-(2-thienyl)propyl)-2-oxazolidinone
• 英文别名: (S)-4-isopropyl-3-{3-(thiophen-2-yl)propanoyl}oxazolidin-2-one
• CAS: 138296-00-1
• 化学式: C₁₃H₁₇NO₃S
• 分子量: 267.349
• InChiKey: OXMRVPGDJJRAET-LLVKDONJSA-N

物化性质

• 沸点：
  426.3±28.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4(S)-(1-methylethyl)-3-(1-oxo-3-(2-thienyl)propyl)-2-oxazolidinone 在 lithium hydroxide 、 双氧水 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.75h， 生成 (2S)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-(thiophen-2-ylmethyl)butanoic acid
  参考文献：
  名称：

  Discovery of non-peptidic P 2 –P 3 butanediamide renin inhibitors with high oral efficacy

  摘要：

  A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P-2 and P-3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4 nM and 2.5 to 7.6 nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3 mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00265-x
• 作为产物：
  描述：

  3-(2-噻吩)丙酸 、 N-lithio-(4S)-4-isopropyl-2-oxazolidone 在 三甲基乙酰氯 、 三乙胺 作用下， 生成 4(S)-(1-methylethyl)-3-(1-oxo-3-(2-thienyl)propyl)-2-oxazolidinone
  参考文献：
  名称：

  Discovery of non-peptidic P 2 –P 3 butanediamide renin inhibitors with high oral efficacy

  摘要：

  A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P-2 and P-3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4 nM and 2.5 to 7.6 nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3 mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00265-x

文献信息

• Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors
  作者：Yasunao Hattori、Kazuya Kobayashi、Ayaka Deguchi、Yukie Nohara、Tomomi Akiyama、Kenta Teruya、Akira Sanjoh、Atsushi Nakagawa、Eiki Yamashita、Kenichi Akaji

  DOI：10.1016/j.bmc.2015.07.023

  日期：2015.9

  A superior substrate sequence for BACE1 containing transition-state mimics at the scissile site was evaluated as a protease inhibitor. Hydroxymethylcarbonyl (HMC) and hydroxyethylamine (HEA) isosteres were selected as the transition state mimics, and incorporated into the scissile site of the superior sequence covering the P4 to P1’ sites (Glu-Ile-Thi-Thi*Nva; *denotes the cleavage site). Isosteres

  易位处含有过渡态模拟物的BACE1的优良底物序列被评估为蛋白酶抑制剂。选择羟甲基羰基（HMC）和羟乙胺（HEA）等位基因作为过渡态模拟物，并将其并入覆盖P 4至P 1 '位的上位序列的易剪位点（Glu-Ile-Thi-Thi * Nva；*表示卵裂位点）。分别合成具有不同的羟基绝对构型的等排体，并评价构型的效果。每个等排异构体的羟基构型均显示出对抑制活性的显着影响。反对-易位部位取代基的构型在HMC型抑制剂中具有有效的抑制活性，而HEA型抑制剂的抗构型则没有抑制活性。基于重组BACE1与每种抑制剂的复合物的X射线晶体学分析进行结构评估，可深入了解蛋白质-配体之间的相互作用，尤其是在主要位点。