5-(羟甲基)-3(2H)-呋喃酮 | 138405-01-3

• 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
• 中文名称: 5-(羟甲基)-3(2H)-呋喃酮
• 中文别名: 1,3-二(3-环己基丙酰氨基)丙-2-基2-(苯基甲氧羰基氨基)乙酸酯
• 英文名称: Benzyloxycarbonylamino-acetic acid 2-(3-cyclohexyl-propionylamino)-1-[(3-cyclohexyl-propionylamino)-methyl]-ethyl ester
• 英文别名: Glycine, N-((phenylmethoxy)carbonyl)-, 2-((3-cyclohexyl-1-oxopropyl)amino)-1-(((3-cyclohexyl-1-oxopropyl)amino)methyl)ethyl ester；1,3-bis(3-cyclohexylpropanoylamino)propan-2-yl 2-(phenylmethoxycarbonylamino)acetate
• CAS: 138405-01-3
• 化学式: C₃₁H₄₇N₃O₆
• 分子量: 557.731
• InChiKey: GFRVVSYNIUQWKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(羟甲基)-3(2H)-呋喃酮 在 palladium on activated charcoal 、 N,N'-二环己基碳二亚胺 、 环己烯 作用下， 以 乙酸乙酯 、 异丙醇 为溶剂， 生成 Glycine, N-(2-((acetylthio)methyl)-1-oxo-3-phenylpropyl)-, 2-((3-cyclohexyl-1-oxopropyl)amino)-1-(((3-cyclohexyl-1-oxopropyl)amino)methyl)ethyl ester, (+-)-
  参考文献：
  名称：

  1,3-Diacylaminopropan-2-ols and Corresponding 2-Acyl Derivatives as Drug Carriers: Unexpected Pharmacological Properties

  摘要：

  脂质载体（伪三酰甘油，PTG）的设计是通过对1,3-二酰基甘油酯基团的酰胺同构取代实现的，其基于与天然三酰甘油的结构相似性，有助于药物在生物膜上的通过。通过急性毒性、放射配体结合和豚鼠回肠实验，考察了2-S-乙酰基硫酚（半乙酰吗啡）伪三酰甘油、Z-甘氨酸伪三酰甘油和1,3-二酰胺丙烷-2-醇载体分子，这些分子因酸侧链的性质而不同。这些评估使我们区分了两种化合物。线性衍生物，如棕榈酰和癸酰，不具有毒性和内在活性。而环状衍生物，则在脂肪酸链中含有苯环、环己烷、环戊烷或金刚烷环，具有额外的性质。半乙酰吗啡的环状衍生物在静脉注射后致死。死亡率受环状载体分子中2-半乙酰吗啡基团的影响。单独的半乙酰吗啡也具有致死作用。环状载体分子及其相关化合物抑制电刺激、组胺或乙酰胆碱诱导的豚鼠回肠收缩反应（非竞争性拮抗），而线性实体和原始化合物则无活性。特别是2-半乙酰吗啡1,3-二金刚烷酰胺PTG呈现出pD'2值7.87±0.29（对组胺）和7.97±0.12（对乙酰胆碱）。

  DOI：

  10.1111/j.2042-7158.1993.tb05530.x

文献信息

• ——
  作者：Didier M. Lambert、Frank Mergen、Catherine F. Berens、Jacques H. Poupaert、Pierre Dumont

  DOI：10.1023/a:1016214506667

  日期：——

  The design of 1,3-diacylaminopropan-2-ols as CNS-directed carrier groups is based on their resemblance to endogenous lipids and the properties of pseudotriglyceride esters to facilitate the brain penetration of therapeutic agents. 2-[S-acetylthiorphan]-1,3-diacylaminopropan-2-ols, differing from the nature of 1,3-acyl chains, were synthesized and evaluated in vivo using the hot-plate jump test. The compounds exhibited naloxone reversible analgesic properties. The effects were superior to those of parent compounds thiorphan and S-acetylthiorphan. The palmitoyl derivative showed also activity at 0.8 mmol/kg after oral administration. Like acetorphan, a thiorphan prodrug, these compounds were poor substrates for brain enkephalinase, suggesting the release of the pharmacological active inhibitor at the site of action in the brain.
• 1,3-Diacylaminopropan-2-ols and Corresponding 2-Acyl Derivatives as Drug Carriers: Unexpected Pharmacological Properties
  作者：D M Lambert、L Neuvens、F Mergen、B Gallez、J H Poupaert、J Ghysel-Burton、J-M Maloteaux、P Dumont

  DOI：10.1111/j.2042-7158.1993.tb05530.x

  日期：2011.4.12

  The design of lipid vectors (pseudotriglycerides, PTGs), achieved by the amide isosteric substitution of the ester moieties of 1,3-diacylglycerols, is based on the structural similarity with natural triglycerides facilitating the passage of pharmacological agents across biological membranes. 2-S-Acetylthiorphan (hemiacetorphan) pseudotriglycerides, Z-glycine pseudotriglycerides and 1,3-diacylaminopropan-2-ols vector molecules differing by the nature of the acid side-chain are examined in acute toxicity, radioligand binding and guinea-pig ileum experiments. These evaluations have led us to distinguish two types of compounds. Linear derivatives, palmitoyl and decanoyl, are devoid of toxicity and intrinsic activity. Cyclic derivatives, which contain in the acyl chain a phenyl, cyclohexyl, cyclopentyl or adamantoyl ring, present additional properties. Cyclic derivatives of hemiacetorphan are lethal after intravenous administration. The mortality is governed by the 2-hemiacetorphan moiety in the cyclic vector molecules. Hemiacetorphan alone is also lethal. Cyclic vector molecules and related compounds inhibit the contractile response of the guinea-pig ileum induced by electrical stimulation, histamine or acetylcholine (noncompetitive antagonism) whereas linear entities and parent compounds are not active. In particular, the 2-hemiacetorphan 1,3-diadamantoylamide PTG presents pD'2 values 7·87 ± 0·29 (vs histamine) and 7·97 ± 0·12 (vs acetylcholine).

  脂质载体（伪三酰甘油，PTG）的设计是通过对1,3-二酰基甘油酯基团的酰胺同构取代实现的，其基于与天然三酰甘油的结构相似性，有助于药物在生物膜上的通过。通过急性毒性、放射配体结合和豚鼠回肠实验，考察了2-S-乙酰基硫酚（半乙酰吗啡）伪三酰甘油、Z-甘氨酸伪三酰甘油和1,3-二酰胺丙烷-2-醇载体分子，这些分子因酸侧链的性质而不同。这些评估使我们区分了两种化合物。线性衍生物，如棕榈酰和癸酰，不具有毒性和内在活性。而环状衍生物，则在脂肪酸链中含有苯环、环己烷、环戊烷或金刚烷环，具有额外的性质。半乙酰吗啡的环状衍生物在静脉注射后致死。死亡率受环状载体分子中2-半乙酰吗啡基团的影响。单独的半乙酰吗啡也具有致死作用。环状载体分子及其相关化合物抑制电刺激、组胺或乙酰胆碱诱导的豚鼠回肠收缩反应（非竞争性拮抗），而线性实体和原始化合物则无活性。特别是2-半乙酰吗啡1,3-二金刚烷酰胺PTG呈现出pD'2值7.87±0.29（对组胺）和7.97±0.12（对乙酰胆碱）。