(4S)-4-(4-fluorophenyl)-1,3-oxazolidine | 1160850-98-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S)-4-(4-fluorophenyl)-1,3-oxazolidine
• CAS: 1160850-98-5
• 化学式: C₉H₁₀FNO
• 分子量: 167.183
• InChiKey: YHKKOWGNRSWIPE-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-4-(4-fluorophenyl)-1,3-oxazolidine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 KMI-1309
  参考文献：
  名称：

  Novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P2 position

  摘要：

  Recently, we reported substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. We also designed and synthesized non-peptidic and small-sized inhibitors possessing a heterocyclic scaffold at the P-2 position. By studying the structure-activity relationship of these inhibitors, we found that the sigma-pi interaction of an inhibitor with the BACE1-Arg235 side chain played a key role in the inhibition mechanism. Hence, we optimized the inhibitors with a focus on their P-2 regions. In this Letter, a series of novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P-2 position are described along with the results of the related structure-activity relationship study. These small-sized inhibitors are expected improved membrane permeability and bioavailability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.089
• 作为产物：
  描述：

  N-boc-4'-fluoro-(S)-phenylglycine methyl ester 在 盐酸 、 锂硼氢 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 生成 (4S)-4-(4-fluorophenyl)-1,3-oxazolidine
  参考文献：
  名称：

  Novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P2 position

  摘要：

  Recently, we reported substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. We also designed and synthesized non-peptidic and small-sized inhibitors possessing a heterocyclic scaffold at the P-2 position. By studying the structure-activity relationship of these inhibitors, we found that the sigma-pi interaction of an inhibitor with the BACE1-Arg235 side chain played a key role in the inhibition mechanism. Hence, we optimized the inhibitors with a focus on their P-2 regions. In this Letter, a series of novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P-2 position are described along with the results of the related structure-activity relationship study. These small-sized inhibitors are expected improved membrane permeability and bioavailability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.089

文献信息

• Significance of interactions of BACE1–Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold
  作者：Yoshio Hamada、Hiroko Ohta、Naoko Miyamoto、Diganta Sarma、Takashi Hamada、Tomoya Nakanishi、Moe Yamasaki、Abdellah Yamani、Shoichi Ishiura、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2009.03.049

  日期：2009.5

  Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P-2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1. (c) 2009 Elsevier Ltd. All rights reserved.