[4-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-phenyl]-(4-chloro-phenyl)-methanone

• 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-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-phenyl]-(4-chloro-phenyl)-methanone
• 英文别名: [4-(1-azabicyclo[2.2.2]octan-3-yloxy)phenyl]-(4-chlorophenyl)methanone
• 化学式: C₂₀H₂₀ClNO₂
• 分子量: 341.837
• InChiKey: PXFAACCCJKQJNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  奎宁环-3-醇 、 4-氯-4'-羟基二苯甲酮 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以22%的产率得到[4-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-phenyl]-(4-chloro-phenyl)-methanone
  参考文献：
  名称：

  Quinuclidine Inhibitors of 2,3-Oxidosqualene Cyclase-Lanosterol Synthase:  Optimization from Lipid Profiles

  摘要：

  Novel 3-substituted quinuclidine inhibitors of cholesterol biosynthesis are reported. Compounds were optimized against oxidosqualene cyclase-lanosterol synthase (OSC) inhibition in vivo, rather than by the conventional optimization of structure-activity relationship information based on in vitro OSC inhibition. Thus; examination of HPLC lipid profiles from orally dosed rats showed cholesterol biosynthetic intermediates and whether cholesterol levels were reduced. A new substituted quinuclidine pharmacophore 18a-c was rapidly found for the inhibition of OSC, and the most promising inhibitors were validated by the confirmation of potent OSC inhibition. Compound 16 gave an IC50 value of 83 +/- 11 nM for human and an IC50 value of 124 +/- 14 nM, for rat, coupled with oral and selective inhibition of cholesterol biosynthesis derived from OSC inhibition (rat, ED50 = 1.3 +/- 0.7 mg/kg, n = 5; marmoset, 15 mg/kg dose, it = 3, caused complete inhibition). These 3-substituted quinuclidines, which were derived from a quinuclidine series previously known to inhibit cholesterol biosynthesis at the squalene synthase step, may afford a novel series of hypocholesterolemic agents acting by the inhibition of OSC.

  DOI：

  10.1021/jm990038q

文献信息

• [EN] METHODS RELATED TO METABOLISM OF PARASITES AND MYCOBACTERIA<br/>[FR] METHODES RELATIVES AU METABOLISME DE PARASITES ET DE MYCOBACTERIES
  申请人：UNIV UTAH RES FOUND

  公开号：WO2000076316A1

  公开（公告）日：2000-12-21

  The present invention relates to the field of microorganism metabolism. In one aspect, the present invention relates to parasite and mycobacterial steroid compound biosynthesis, including methods to inhibit the steroid compound biosynthesis. The present invention therefore relates broadly to microbiology, pharmaceutical chemistery, and disease treatments.