LASSBio-730 | 138262-29-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: LASSBio-730
• 英文别名: 1-phenyl-4-(4-phenylbutyl)piperazine；1-Phenyl-4-(4-phenyl-butyl)-piperazine
• CAS: 138262-29-0
• 化学式: C₂₀H₂₆N₂
• 分子量: 294.44
• InChiKey: BGDZXIKVCVQJFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-苯基丁酰氯 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 LASSBio-730
  参考文献：
  名称：

  Novel 1-phenylpiperazine and 4-phenylpiperidine derivatives as high-affinity .sigma. ligands

  摘要：

  Sigma-receptors may represent an exciting new approach for the development of novel psychotherapeutic agents. Unfortunately, many of the commonly used sigma-ligands lack selectivity (e.g., many bind at phencyclidine or dopamine receptors) or suffer from other serious drawbacks. Recently, we described a series of 2-phenylaminoethanes that bind at sigma-receptors with high affinity and selectivity. Because there is evidence that 1-phenylpiperazines can structurally mimic the 2-phenylaminoethane moiety, we prepared a series of 1-phenylpiperazines and related analogues and incorporated structural features already shown to enhance the sigma-binding of the 2-phenylaminoethanes. Several of these derivatives bind at sigma-receptors with high affinity (K(i) = 1-10 nM) and lack appreciable affinity for phencyclidine and dopamine receptors. In as much as certain of these agents structurally resemble the high-affinity, but nonselective, sigma-ligand haloperidol, and because they bind with 10 times the affinity of haloperidol, we have apparently identified what appears to be the primary sigma-pharmacophore of that agent.

  DOI：

  10.1021/jm00116a003

文献信息

• Coordination assembly enables highly selective catalytic hydroaminomethylation of olefins
  作者：Chun Qian、Qingshu Zheng、Jie Chen、Bo Tu、Tao Tu

  DOI：10.1039/d2gc04195b

  日期：——

  produce amines, but control of the selectivity between linear and branched products is still challenging. Herein, a series of solid main-chain NHC–rhodium(I) polymers prepared by coordination assembly were found to be highly efficient single-site catalysts in the HAM of olefins. A dramatic enhancement of both productivity (up to 98% yield) and linear selectivity (up to 99 : 1) was observed, largely

  烯烃的加氢氨甲基化 (HAM) 是生产胺类最有前途和最实用的方法之一，但控制线性和支化产物之间的选择性仍然具有挑战性。在此，发现一系列通过配位组装制备的固体主链 NHC-铑 ( I ) 聚合物是烯烃 HAM 中的高效单中心催化剂。观察到生产率（高达 98% 的收率）和线性选择性（高达 99:1）的显着提高，这主要是由于固体催化剂的扩展配位组装结构所施加的限制。除了广泛的底物范围外，创纪录的营业额为 2.1 × 10 5实现了，固体催化剂可以重复使用18次以上，活性和选择性没有明显损失。该协议对敏感官能团具有很高的容忍度，其实用性体现在直接从烯丙醇或杂环胺合成几种领先的药物，无需任何保护或脱保护操作，规模可达一克。
• Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-Adrenergic receptor blocking properties
  作者：Luiz A.S. Romeiro、Marcos da Silva Ferreira、Leandro L. da Silva、Helena C. Castro、Ana L.P. Miranda、Cláudia L.M. Silva、François Noël、Jéssica B. Nascimento、Claudia V. Araújo、Eduardo Tibiriçá、Eliezer J. Barreiro、Carlos A.M. Fraga

  DOI：10.1016/j.ejmech.2011.04.032

  日期：2011.7

  We described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl)-4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [(3)H]prazosin binding. We obtained Ki values of 0.14 nM for the alpha 1A-AR, similar to that displayed by tamsulosin (K(i) = 0.13 nM) and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher affinity for alpha 1A-AR. LASSBio-772 also presented high affinity (K(B) = 0.025 nM) for the alpha 1D-AR subtype in the functional rat aorta assay, showing to be equipotent to tamsulosin (K(B) = 0.017 nM). (C) 2011 Elsevier Masson SAS. All rights reserved.
• Novel 1-phenylpiperazine and 4-phenylpiperidine derivatives as high-affinity .sigma. ligands
  作者：Richard A. Glennon、Mamoun Y. Yousif、Abd M. Ismaiel、Mahmoud B. El-Ashmawy、J. L. Herndon、James B. Fischer、Alfred C. Server、Kathleen J. Burke Howie

  DOI：10.1021/jm00116a003

  日期：1991.12

  Sigma-receptors may represent an exciting new approach for the development of novel psychotherapeutic agents. Unfortunately, many of the commonly used sigma-ligands lack selectivity (e.g., many bind at phencyclidine or dopamine receptors) or suffer from other serious drawbacks. Recently, we described a series of 2-phenylaminoethanes that bind at sigma-receptors with high affinity and selectivity. Because there is evidence that 1-phenylpiperazines can structurally mimic the 2-phenylaminoethane moiety, we prepared a series of 1-phenylpiperazines and related analogues and incorporated structural features already shown to enhance the sigma-binding of the 2-phenylaminoethanes. Several of these derivatives bind at sigma-receptors with high affinity (K(i) = 1-10 nM) and lack appreciable affinity for phencyclidine and dopamine receptors. In as much as certain of these agents structurally resemble the high-affinity, but nonselective, sigma-ligand haloperidol, and because they bind with 10 times the affinity of haloperidol, we have apparently identified what appears to be the primary sigma-pharmacophore of that agent.