3,4-Dihydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)naphthalenone | 667900-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3,4-Dihydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)naphthalenone
• 英文别名: 6-phenylmethoxy-2-[2-(4-phenylpiperidin-1-yl)ethyl]-3,4-dihydro-2H-naphthalen-1-one
• CAS: 667900-23-4
• 化学式: C₃₀H₃₃NO₂
• 分子量: 439.598
• InChiKey: CYZOBDVPCDGVGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-Dihydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)naphthalenone 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 以88%的产率得到3,4-Dihydro-6-hydroxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)naphthalenone
  参考文献：
  名称：

  Tetrahydronaphthalene-derived amino alcohols and amino ketones as potent and selective inhibitors of the delayed rectifier potassium current IKs

  摘要：

  Class III anti-arrhythmic drugs (e.g., dofetilide) prolong cardiac action potential duration (APD) by blocking the fast component of the delayed rectifier potassium current (I-Kr). The block of I-Kr can result in life threatening ventricular arrhythmias (i.e., torsades de pointes). Unlike I-Kr, the role of the slow component of the delayed rectifier potassium current (I-Ks) becomes significant only at faster heart rate. Therefore selective blockers Of I-Ks could prolong APD with a reduced propensity to cause proarrhythmic side effects. This report describes structure-activity relationships (SARs) of a series of I-Ks inhibitors derived from 6-alkoxytetralones with good in vitro activity (IC50 > 30 nM) and up to 40-fold I-Ks/I-Kr selectivity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.003
• 作为产物：
  描述：

  6-羟基-1-四氢萘酮 在 N-甲基吗啉 、 六甲基磷酰三胺 、 氢氧化钾 、 lithium aluminium tetrahydride 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 戴斯-马丁氧化剂 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 3,4-Dihydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)naphthalenone
  参考文献：
  名称：

  Tetrahydronaphthalene-derived amino alcohols and amino ketones as potent and selective inhibitors of the delayed rectifier potassium current IKs

  摘要：

  Class III anti-arrhythmic drugs (e.g., dofetilide) prolong cardiac action potential duration (APD) by blocking the fast component of the delayed rectifier potassium current (I-Kr). The block of I-Kr can result in life threatening ventricular arrhythmias (i.e., torsades de pointes). Unlike I-Kr, the role of the slow component of the delayed rectifier potassium current (I-Ks) becomes significant only at faster heart rate. Therefore selective blockers Of I-Ks could prolong APD with a reduced propensity to cause proarrhythmic side effects. This report describes structure-activity relationships (SARs) of a series of I-Ks inhibitors derived from 6-alkoxytetralones with good in vitro activity (IC50 > 30 nM) and up to 40-fold I-Ks/I-Kr selectivity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.003

文献信息

• US6048877A
  申请人：——

  公开号：US6048877A

  公开（公告）日：2000-04-11
• [EN] TETRALONE DERIVATIVES AS ANTIARRHYTHMIC AGENTS<br/>[FR] DERIVES DE TETRALONE UTILISES COMME AGENTS ANTIARYTHMIQUES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1998036749A1

  公开（公告）日：1998-08-27

  (EN) Tetralone derivatives of formula (I) where R1 is halo, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, (aryl)alkenyl, (aryl)alkynyl, alkoxy, O-alkenyl, O-aryl, O-alkyl(heterocyclo), COO-alkyl, alkanoyl, CO-amino, CO-substituted amino, alkyl-CO-amino, alkyl-CO-substituted amino, NHCO-alkyl, NHCO-aryl, NHCO-alkyl(heterocyclo), N(alkyl)CO-alkyl, N(alkyl)CO-aryl, N(alkyl)CO-heterocyclo, N(alkyl)CO-alkyl(heterocyclo); R2 is hydrogen, alkyl, halo, aryl, alkoxy, amino, substituted amino; R3 is oxo, hydroxy, alkoxy, O-COalkyl, -O-COaryl, -O-COheterocyclo, NOH, NO-alkyl, N-amino, N-substituted amino, N-NHCONHalkyl, N-NHSO2alkyl, N-NHSO2aryl, amino, substituted amino, NHCO-alkyl, NHCO-aryl, NHCO-heterocyclo, spiroheterocyclo; R4 is hydrogen, alkyl, alkyl(COalkyl), alkyl(COOalkyl); or R3 and R4 taken together with the atoms to which they are attached form a five- to seven-membered ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulfur; R5 is hydrogen, alkyl, alkenyl, alkyl(heterocyclo), alkyl-NHCO(alkyl), alkyl-NHCO(aryl), alkyl-NHCO(heterocyclo), alkyl-NHCO(alkylheterocyclo); and n is an integer of 0 to 2. These compounds have been found to be useful in the treatment of arrhythmia.(FR) L'invention concerne des dérivés de la formule (I), dans laquelle: R1 représente halo, alkyle, alcényle, alkynyle, cycloalkyle, aryle, (aryl)alcényle, (aryl)alkynyle, alcoxy, O-alcényle, O-aryle, O-alkyle(hétérocyclo), COO-alkyle, alcanoyle, CO-amino, CO-amino substitué, alkyl-CO-amino, alkyl-CO-amino substitué, NHCO-alkyle, NHCO-aryle, NHCO-alkyl(hétérocyclo), N(alkyl)CO-alkyle, N(alkyl)CO-aryle, N(alkyl)CO-hétérocyclo, N(alkyl)CO-alkyl(hétérocyclo); R2 représente hydrogène, alkyle, halo, aryle, alcoxy, amino, amino substitué; R3 représente oxo, hydroxy, alcoxy, O-COalkyle, -O-COaryle, -O-COhétérocyclo, NOH, NO-alkyle, N-amino, N-amino substitué, N-NHCONHalkyle, N-NHSO2alkyle, N-NHSO2aryle, amino, amino substitué, NHCO-alkyle, NHCO-aryle, NHCO-hétérocyclo, spirohétérocyclo; R4 représente hydrogène, alkyle, alkyl(COalkyle), alkyl(COOalkyle); ou bien R3 et R4 pris ensemble forment avec les atomes auxquels ils sont fixés un cycle comportant cinq à sept éléments et pouvant contenir jusqu'à trois hétéroatomes choisis parmi oxygène, azote et soufre; R5 représente hydrogène, alkyle, alcényle, alkyl(hétérocyclo), alkyl-NHCO(alkyle), alkyl-NHCO(aryle), alkyl-NHCO(hétérocyclo), alkyl-NHCO(alkylhétérocyclo); et n est un nombre entier pouvant aller de 0 à 2. Lesdits composés se sont montrés utiles dans le traitement de l'arythmie.