(4-bromophenyl)-[4-(6-cyclopropylaminohexyloxy)phenyl]methanone | 579816-00-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-bromophenyl)-[4-(6-cyclopropylaminohexyloxy)phenyl]methanone
• 英文别名: (4-Bromophenyl)-[4-[6-(cyclopropylamino)hexoxy]phenyl]methanone
• CAS: 579816-00-5
• 化学式: C₂₂H₂₆BrNO₂
• 分子量: 416.358
• InChiKey: LMSNPWMDLFMFGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 (4-bromophenyl)-[4-(6-cyclopropylaminohexyloxy)phenyl]methanone 在 sodium dihydrogen phosphate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.0h， 以85%的产率得到[6-[6-(cyclopropylmethylamino)hexyloxy]phenyl](4-bromophenyl)methanone
  参考文献：
  名称：

  Synthesis and Structure−Activity Studies of Novel Orally Active Non-Terpenoic 2,3-Oxidosqualene Cyclase Inhibitors

  摘要：

  New orally active non-terpenoic inhibitors of human 2,3-oxidosqualene cyclase (hOSC) are reported. The starting point for the optimization process was a set of compounds derived from a fungicide project, which in addition to showing high affinity for OSC from Candida albicans showed also high affinity for human OSC. Common structural elements of these inhibitors are an amine residue and an electrophilic carbonyl C atom embedded in a benzophenone system, which are at a distance of about 10.7 Angstrom. Considering that the keto moiety is in a potentially labile position, modifications of the substitution pattern at the benzophenone as well as annelated heteroaryl systems were explored. Our approach combined testing of the compounds first for increased binding affinity and for increased stability in vitro. Most promising compounds were then evaluated for their efficacy in lowering plasma total cholesterol (TC) and plasma low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic hamsters. In this respect, the most promising compounds are the benzophenone derivative 1.fumarate and the benzo[d]-isothiazol 24.fumarate, which lowered TC by 40% and 33%, respectively.

  DOI：

  10.1021/jm021120f
• 作为产物：
  描述：

  4-羟基苯基-(4-溴-苯基)-甲酮 在 氢氧化钾 、 sodium hydroxide 、 四丁基溴化铵 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 126.0h， 生成 (4-bromophenyl)-[4-(6-cyclopropylaminohexyloxy)phenyl]methanone
  参考文献：
  名称：

  Synthesis and Structure−Activity Studies of Novel Orally Active Non-Terpenoic 2,3-Oxidosqualene Cyclase Inhibitors

  摘要：

  New orally active non-terpenoic inhibitors of human 2,3-oxidosqualene cyclase (hOSC) are reported. The starting point for the optimization process was a set of compounds derived from a fungicide project, which in addition to showing high affinity for OSC from Candida albicans showed also high affinity for human OSC. Common structural elements of these inhibitors are an amine residue and an electrophilic carbonyl C atom embedded in a benzophenone system, which are at a distance of about 10.7 Angstrom. Considering that the keto moiety is in a potentially labile position, modifications of the substitution pattern at the benzophenone as well as annelated heteroaryl systems were explored. Our approach combined testing of the compounds first for increased binding affinity and for increased stability in vitro. Most promising compounds were then evaluated for their efficacy in lowering plasma total cholesterol (TC) and plasma low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic hamsters. In this respect, the most promising compounds are the benzophenone derivative 1.fumarate and the benzo[d]-isothiazol 24.fumarate, which lowered TC by 40% and 33%, respectively.

  DOI：

  10.1021/jm021120f

文献信息

• Synthesis and Structure−Activity Studies of Novel Orally Active Non-Terpenoic 2,3-Oxidosqualene Cyclase Inhibitors
  作者：Henrietta Dehmlow、Johannes D. Aebi、Synèse Jolidon、Yu-Hua Ji、Elisabeth M. von der Mark、Jacques Himber、Olivier H. Morand

  DOI：10.1021/jm021120f

  日期：2003.7.1

  New orally active non-terpenoic inhibitors of human 2,3-oxidosqualene cyclase (hOSC) are reported. The starting point for the optimization process was a set of compounds derived from a fungicide project, which in addition to showing high affinity for OSC from Candida albicans showed also high affinity for human OSC. Common structural elements of these inhibitors are an amine residue and an electrophilic carbonyl C atom embedded in a benzophenone system, which are at a distance of about 10.7 Angstrom. Considering that the keto moiety is in a potentially labile position, modifications of the substitution pattern at the benzophenone as well as annelated heteroaryl systems were explored. Our approach combined testing of the compounds first for increased binding affinity and for increased stability in vitro. Most promising compounds were then evaluated for their efficacy in lowering plasma total cholesterol (TC) and plasma low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic hamsters. In this respect, the most promising compounds are the benzophenone derivative 1.fumarate and the benzo[d]-isothiazol 24.fumarate, which lowered TC by 40% and 33%, respectively.