tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-4-oxo-4-(piperidin-1-yl)butylsulfanyl]pentanoate | 1448177-10-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-4-oxo-4-(piperidin-1-yl)butylsulfanyl]pentanoate
• 英文别名: Tert-butyl 5-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-piperidin-1-ylbutyl]sulfanylpentanoate；tert-butyl 5-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-piperidin-1-ylbutyl]sulfanylpentanoate
• CAS: 1448177-10-3
• 化学式: C₂₃H₄₂N₂O₅S
• 分子量: 458.663
• InChiKey: RAQXJFIGHNYGMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-4-oxo-4-(piperidin-1-yl)butylsulfanyl]pentanoate 、 三氟乙酸 以 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 以76%的产率得到5-[3-(R,S)-3-Amino-4-(carboxyhydrazide)butylsulfanyl]pentanoic acid ditrifluoroacetate salt
  参考文献：
  名称：

  The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

  摘要：

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.039
• 作为产物：
  描述：

  DL-蛋氨酸 在 氨 、 sodium 、 氯甲酸乙酯 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-4-oxo-4-(piperidin-1-yl)butylsulfanyl]pentanoate
  参考文献：
  名称：

  The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

  摘要：

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.039