1-<3-(2-methoxyethoxymethyl)phenyl>-3-methylbutanol | 219502-49-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-<3-(2-methoxyethoxymethyl)phenyl>-3-methylbutanol
• 英文别名: 1-[3-(2-Methoxyethoxymethoxy)phenyl]-3-methylbutan-1-ol
• CAS: 219502-49-5
• 化学式: C₁₅H₂₄O₄
• 分子量: 268.353
• InChiKey: GHNMQGBBPJEJLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<3-(2-methoxyethoxymethyl)phenyl>-3-methylbutanol 在 四氯化碳 、 三苯基膦 作用下， 反应 3.0h， 以80%的产率得到1-chloro-1-<3-(2-methoxyethoxymethyl)phenyl>-3-methylbutane
  参考文献：
  名称：

  De Novo Design, Synthesis, and Biological Activities of High-Affinity and Selective Non-Peptide Agonists of the δ-Opioid Receptor

  摘要：

  On the basis of the structure-activity relationships of delta-opioid-selective peptide ligands and on a model of the proposed bioactive conformation for a potent and selective, conformationally constrained delta-opioid peptide ligand [(2S,3R)-TMT1]DPDPE, a series of small organic peptide mimetic compounds targeted for the delta-opioid receptor have been designed, synthesized, and evaluated in radiolabeled ligand binding assays and in vitro bioassays. The new non-peptide ligands use piperazine as a template to present the most important pharmacophore groups, including phenol and phenyl groups and a hydrophobic moiety. This hydrophobic group was designed to mimic the hydrophobic character of the D-Pen residues in DPDPE, which has been found to be extremely important for increasing the binding affinity and selectivity of these non-peptide ligands for the delta-opioid receptor over the mu-opioid receptor. Compound 6f (SL-3111) showed 8 nM binding affinity and over 2000-fold selectivity for the delta-opioid receptor over the delta-opioid receptor. Both enantiomers of SL-3111 were separated, and the (-)-isomer was shown to be the compound with the highest affinity for the delta-opioid receptor found in our study (IC50 = 4.1 nM), with a selectivity very similar to that observed for the racemic compound. The phenol hydroxyl group of SL-3111 turned out to be essential to maintain high affinity for the delta-opioid receptor, which also was observed in the case of the delta-opioid-selective peptide ligand DPDPE. Binding studies of SL-3111 and [p-C1Phe(4)]DPDPE on the cloned wild-type and mutated human delta-opioid receptors suggested that the new non-peptide ligand has a binding profile similar to that of DPDPE but different from that of (+)-4-[((alpha R)-alpha(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl] -N,N-diethylbenzamide (SNC-80), another; delta-opioid-selective non-peptide ligand.

  DOI：

  10.1021/jm980374r
• 作为产物：
  描述：

  间羟基苯甲醛 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-<3-(2-methoxyethoxymethyl)phenyl>-3-methylbutanol
  参考文献：
  名称：

  De Novo Design, Synthesis, and Biological Activities of High-Affinity and Selective Non-Peptide Agonists of the δ-Opioid Receptor

  摘要：

  On the basis of the structure-activity relationships of delta-opioid-selective peptide ligands and on a model of the proposed bioactive conformation for a potent and selective, conformationally constrained delta-opioid peptide ligand [(2S,3R)-TMT1]DPDPE, a series of small organic peptide mimetic compounds targeted for the delta-opioid receptor have been designed, synthesized, and evaluated in radiolabeled ligand binding assays and in vitro bioassays. The new non-peptide ligands use piperazine as a template to present the most important pharmacophore groups, including phenol and phenyl groups and a hydrophobic moiety. This hydrophobic group was designed to mimic the hydrophobic character of the D-Pen residues in DPDPE, which has been found to be extremely important for increasing the binding affinity and selectivity of these non-peptide ligands for the delta-opioid receptor over the mu-opioid receptor. Compound 6f (SL-3111) showed 8 nM binding affinity and over 2000-fold selectivity for the delta-opioid receptor over the delta-opioid receptor. Both enantiomers of SL-3111 were separated, and the (-)-isomer was shown to be the compound with the highest affinity for the delta-opioid receptor found in our study (IC50 = 4.1 nM), with a selectivity very similar to that observed for the racemic compound. The phenol hydroxyl group of SL-3111 turned out to be essential to maintain high affinity for the delta-opioid receptor, which also was observed in the case of the delta-opioid-selective peptide ligand DPDPE. Binding studies of SL-3111 and [p-C1Phe(4)]DPDPE on the cloned wild-type and mutated human delta-opioid receptors suggested that the new non-peptide ligand has a binding profile similar to that of DPDPE but different from that of (+)-4-[((alpha R)-alpha(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl] -N,N-diethylbenzamide (SNC-80), another; delta-opioid-selective non-peptide ligand.

  DOI：

  10.1021/jm980374r

文献信息

• De Novo Design, Synthesis, and Biological Activities of High-Affinity and Selective Non-Peptide Agonists of the δ-Opioid Receptor
  作者：Subo Liao、Josue Alfaro-Lopez、Mark D. Shenderovich、Keiko Hosohata、Jun Lin、Xiaoping Li、Dagmar Stropova、Peg Davis、Kevin A. Jernigan、Frank Porreca、Henry I. Yamamura、Victor J. Hruby

  DOI：10.1021/jm980374r

  日期：1998.11.1

  On the basis of the structure-activity relationships of delta-opioid-selective peptide ligands and on a model of the proposed bioactive conformation for a potent and selective, conformationally constrained delta-opioid peptide ligand [(2S,3R)-TMT1]DPDPE, a series of small organic peptide mimetic compounds targeted for the delta-opioid receptor have been designed, synthesized, and evaluated in radiolabeled ligand binding assays and in vitro bioassays. The new non-peptide ligands use piperazine as a template to present the most important pharmacophore groups, including phenol and phenyl groups and a hydrophobic moiety. This hydrophobic group was designed to mimic the hydrophobic character of the D-Pen residues in DPDPE, which has been found to be extremely important for increasing the binding affinity and selectivity of these non-peptide ligands for the delta-opioid receptor over the mu-opioid receptor. Compound 6f (SL-3111) showed 8 nM binding affinity and over 2000-fold selectivity for the delta-opioid receptor over the delta-opioid receptor. Both enantiomers of SL-3111 were separated, and the (-)-isomer was shown to be the compound with the highest affinity for the delta-opioid receptor found in our study (IC50 = 4.1 nM), with a selectivity very similar to that observed for the racemic compound. The phenol hydroxyl group of SL-3111 turned out to be essential to maintain high affinity for the delta-opioid receptor, which also was observed in the case of the delta-opioid-selective peptide ligand DPDPE. Binding studies of SL-3111 and [p-C1Phe(4)]DPDPE on the cloned wild-type and mutated human delta-opioid receptors suggested that the new non-peptide ligand has a binding profile similar to that of DPDPE but different from that of (+)-4-[((alpha R)-alpha(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl] -N,N-diethylbenzamide (SNC-80), another; delta-opioid-selective non-peptide ligand.