tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-3-cyanopropylsulfanyl]pentanoate | 1448177-30-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-3-cyanopropylsulfanyl]pentanoate
• 英文别名: Tert-butyl 5-[3-cyano-3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]sulfanylpentanoate；tert-butyl 5-[3-cyano-3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]sulfanylpentanoate
• CAS: 1448177-30-7
• 化学式: C₁₈H₃₂N₂O₄S
• 分子量: 372.529
• InChiKey: IEJGBIMOECBSKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  114
• 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)-3-cyanopropylsulfanyl]pentanoate 在 sodium azide 、 zinc dibromide 作用下， 以 水 、 异丙醇 为溶剂， 以65%的产率得到tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-3-(1H-tetrazol-5-yl)propylsulfanyl]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
• 作为产物：
  描述：

  tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-4-(carboxamide)butylsulfanyl] pentanoate 在 吡啶 、 三氟乙酸酐 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以77%的产率得到tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-3-cyanopropylsulfanyl]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

文献信息

• The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
  作者：Jan Pícha、Václav Vaněk、Miloš Buděšínský、Jana Mládková、Timothy A. Garrow、Jiří Jiráček

  DOI：10.1016/j.ejmech.2013.04.039

  日期：2013.7

  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.