4-[2-羟基-3-[4-(2-甲氧基苯基)哌嗪-1-基]丙氧基]萘-1-醇 | 133024-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-[2-羟基-3-[4-(2-甲氧基苯基)哌嗪-1-基]丙氧基]萘-1-醇
• 英文名称: (naphthyl)hydroxy-naftopidil
• 英文别名: 1-(4-(2-methoxyphenyl)piperazin-1-yl)-3-(4-hydroxynaphthalen-1-yloxy)propan-2-ol；1-(2-methoxyphenyl)-4-[3-(4-hydroxynaphth-1-yloxy)-2-hydroxypropyl]-piperazine；NH-Naftopidil；4-[2-hydroxy-3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy]naphthalen-1-ol
• CAS: 133024-36-9
• 化学式: C₂₄H₂₈N₂O₄
• 分子量: 408.497
• InChiKey: YSVLPXXMZYGJCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-Benzyloxy-4-hydroxynaphthalene 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成 4-[2-羟基-3-[4-(2-甲氧基苯基)哌嗪-1-基]丙氧基]萘-1-醇
  参考文献：
  名称：

  Identification of HUHS190, a human naftopidil metabolite, as a novel anti-bladder cancer drug

  摘要：

  We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1, which exhibited the most selective toxicities between against normal and cancer cells (Table 1). 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 mu M in saline for an intravesical instillation drug. Moreover, serum concentration of 2 was comparable to that of 1, an oral preparation drug, after oral administration at 32 mg/kg (Fig. 3). Both of 1 and 2 showed broad-spectrum anti-cancer activities in vitro, for example, 1 and 2 showed inhibitory activity IC50 = 21.1 mu M and 17.2 mu M for DU145, human prostate cancer cells, respectively, and IC50 = 18.5 mu M and 10.5 mu M for T24 cells, human bladder cancer cells. In this study, we estimated anticancer effects of 2 in a bladder cancer model after intravesical administration similar to clinical cases. A single intravesical administration of 2 exhibited the most potent inhibitory activities among the clinical drugs for bladder cancers, BCG and Pirarubicin, without obvious side effects and toxicity (Fig. 4). Thus, HUHS190 (2) can be effective for patients after post-TURBT therapy of bladder cancer without side effects, unlike the currently available clinical drugs.

  DOI：

  10.1016/j.bmcl.2019.126744

文献信息

• Niebch; Locher; Peter, Arzneimittel-Forschung/Drug Research, 1991, vol. 41, # 10, p. 1027 - 1032
  作者：Niebch、Locher、Peter、Borbe

  DOI：——

  日期：——
• Hydroxylierte 1-Phenyl-4-[3-(naphth-1-yl-oxy)-2-hydroxypropyl]-piperazine, Verfahren zu ihrer Herstellung sowie Arzneimittel, die diese Verbindungen enthalten
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0401652B1

  公开（公告）日：1994-08-17
• US5037828A
  申请人：——

  公开号：US5037828A

  公开（公告）日：1991-08-06