O-desmethyl-naftopidil | 133347-36-1

• 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: O-desmethyl-naftopidil
• 英文别名: 1-<1-(2-Hydroxyphenyl)piperazin-4-yl>-3-(1-naphthyloxy)-2-propanol；1-(4-(2-hydroxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy)propan-2-ol；O-desmethyl-naftodipil；1-(2-hydroxyphenyl)-4-[3-(naphth-1-yloxy)-2-hydroxypropyl]-piperazine；2-(4-(2-Hydroxy-3-(naphthalen-1-yloxy)propyl)piperazin-1-YL)phenol；2-[4-(2-hydroxy-3-naphthalen-1-yloxypropyl)piperazin-1-yl]phenol
• CAS: 133347-36-1
• 化学式: C₂₃H₂₆N₂O₃
• 分子量: 378.471
• InChiKey: SRBVIBLTYWRHJQ-UHFFFAOYSA-N

物化性质

• 沸点：
  613.6±55.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  萘酚 在 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 O-desmethyl-naftopidil
  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

• Synthese von potentiellen Naftopidil-Metaboliten
  作者：Bernhard Kutscher、Jürgen Engel、Ilona Fleischhauer、Georg Niebch

  DOI：10.1002/ardp.19933261007

  日期：——

  Es wird über die Synthese von vier potentiellen Metaboliten [Desmethyl‐Naftopidil (1), 4‐(Phenyl)‐hydroxy‐Naftopidil (2), 4‐(Naphthyl)‐hydroxy‐Naftopidil (3), Desanaphthyl‐Naftopidil (4)] des selektiven α1‐Antagonisten Naftopidil berichtet.

  它是通过四种潜在代谢物的合成来描述的 [desmethyl-naftopidil (1), 4- (phenyl)-hydroxy-naftopidil (2), 4- (naphthyl)-hydroxy-naftopidil (3), desanaphthyl-naftopidil (4) ] 选择性 α1 拮抗剂萘哌地尔。
• Piperazine derivatives, uses thereof and pharmaceutical compositions
  申请人：Boehringer Mannheim GmbH

  公开号：US05037828A1

  公开（公告）日：1991-08-06

  The present invention provides compounds of the general formula: ##STR1## wherein R.sub.1 is a hydroxyl group or a methoxy radical, R.sub.2 is a hydrogen atom or a hyroxyl group and R.sub.3 is a hydrogen atom or a hydroxyl group, with the proviso that R.sub.2 and R.sub.3 are not simultaneously hydrogen atoms when R.sub.1 is a methoxy radical; and the pharmacologically acceptable salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them.

  本发明提供了一类通式为##STR1##的化合物，其中R1是羟基或甲氧基，R2是氢原子或羟基，R3是氢原子或羟基，但条件是当R1为甲氧基时，R2和R3不同时为氢原子；以及这些化合物的药学上可接受的盐。本发明还提供了制备这些化合物的方法和含有这些化合物的药物组合物。
• 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