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.
• Tetrahydronaphthalene-derived amino alcohols and amino ketones as potent and selective inhibitors of the delayed rectifier potassium current IKs
  作者：Saleem Ahmad、Lidia Doweyko、Aaila Ashfaq、Francis N. Ferrara、Sharon N. Bisaha、Joan B. Schmidt、John DiMarco、Mary Lee Conder、Tonya Jenkins-West、Diane E. Normandin、Anita D. Russell、Mark A. Smith、Paul C. Levesque、Nicholas J. Lodge、John Lloyd、Philip D. Stein、Karnail S. Atwal

  DOI：10.1016/j.bmcl.2003.10.003

  日期：2004.1

  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.