(+/-)-1-benzyloxy-4-(oxiranylmethoxy)naphthalene | 133024-37-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (+/-)-1-benzyloxy-4-(oxiranylmethoxy)naphthalene
• 英文别名: 2-((4-benzyloxynaphthalen-1-yloxy)methyl)oxirane；1-Benzyloxy-4-(2,3-epoxypropyl)-naphthylether；2-[(4-Phenylmethoxynaphthalen-1-yl)oxymethyl]oxirane
• CAS: 133024-37-0
• 化学式: C₂₀H₁₈O₃
• 分子量: 306.361
• InChiKey: SIICEJALUOOTQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-1-benzyloxy-4-(oxiranylmethoxy)naphthalene 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~60.0 ℃ 、101.33 kPa 条件下， 反应 39.0h， 生成 3-(4-hydroxynaphthalen-1-yloxy)-1-(4-(2-hydroxyphenyl)piperazin-1-yl)propan-2-ol
  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
• 作为产物：
  描述：

  1,4-二羟基萘 在 吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 水 、 potassium carbonate 、 cesium fluoride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.33h， 生成 (+/-)-1-benzyloxy-4-(oxiranylmethoxy)naphthalene
  参考文献：
  名称：

  Synthesis of enantiomeric 4-hydroxypropranolols from 1,4-dihydroxynaphthalene

  摘要：

  Both (R)- and (S)-enantiomes of 4-hydroxypropranolol were effectively prepared from 1,4-dihydroxynaphthalene in eight steps. The overall yields were around 30%. (C) 2001 Elsevier Science Ltd. All rights, reserved.

  DOI：

  10.1016/s0957-4166(01)00122-7

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。