(4-Methyl-benzhydryl)-malonsaeure-diaethylester | 855658-67-2

• 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-Methyl-benzhydryl)-malonsaeure-diaethylester
• 英文别名: (4-methyl-benzhydryl)-malonic acid diethyl ester；Diethyl 2-[(4-methylphenyl)-phenylmethyl]propanedioate
• CAS: 855658-67-2
• 化学式: C₂₁H₂₄O₄
• 分子量: 340.419
• InChiKey: ULRVIQPTHHTPFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-Methyl-benzhydryl)-malonsaeure-diaethylester 在 4-二甲氨基吡啶 、 氢氧化钾 、 lithium aluminium tetrahydride 、 氯化亚砜 、 potassium iodide 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 17.17h， 生成 4-phenyl-4-p-tolyl-butyronitrile
  参考文献：
  名称：

  Ring-substituted histaprodifen analogues as partial agonists for histamine H1 receptors: synthesis and structure–activity relationships

  摘要：

  Thirteen racemic benzene ring-substituted analogues of histaprodifen (8a; 2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine), a novel lead for potent and selective histamine H-1-receptor agonists, have been prepared from substituted 4,4-diphenylbutyronitriles 5 via cyclization of the corresponding methyl butyrimidates 6 with 2-oxo-4-phthalimido-1-butyl acetate in liquid ammonia, followed by deprotection. Nitriles 5 were accessible by alkylation of either substituted diphenylmethanes with 3-bromopropionitrile or diethyl malonate with substituted 1-chloro-diphenylmethanes and subsequent standard reactions. The title compounds 8 displayed partial agonism on contractile H-1 receptors of the guinea-pig ileum (E-max = 2-98% relative to histamine) and, compared with the endogenous agonist, were endowed with agonist potencies of 4-92%. The meta fluorinated (gc) and meta chlorinated (8f) analogues showed the highest relative potency in this series (95% confidence Limits 85-99% and 78-102%), but did not exceed the value of the lead 8a (99-124%). Compound 8c (2-[2-[3-(3-fluorophenyl)-3-phenylpropyl]-1H-imidazol-4-yl]ethanamine) was a partial agonist at contractile H-1 receptors of the guinea-pig aorta (relative potency 154% vs. 100% for histamine) and at relaxation-mediating endothelial H-1 receptors of the rat aorta (relative potency 556% vs. 100% for histamine) and matched with the functional behaviour of 8a. Agonism observed for each compound was sensitive to blockade by the selective H-1-receptor antagonist mepyramine (pA(2) approximate to 9 (guinea-pig) and pA(2) approximate to 8 (rat aorta)). All histaprodifen analogues 8 stimulated neither histaminergic H-2/H-3, nor cholinergic M-3 receptors. They displayed only low to moderate affinity for these sites (H-2: pD'(2), < 5; H-3/M-3: pA(2) < 6). With regard to the substitution pattern on the benzene ring, there was no correlation between the histaprodifen series and the corresponding derivatives of another selective H-1-receptor agonist, viz. 2-phenylhistamine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00105-7
• 作为产物：
  描述：

  亚苯甲基丙二酸二乙酯 、 对甲苯基溴化镁 在 copper(I) bromide 作用下， 生成 (4-Methyl-benzhydryl)-malonsaeure-diaethylester
  参考文献：
  名称：

  The Synthesis and Ionization Constants of the Six Aminobenzo [c]phenanthrenes

  摘要：

  DOI：

  10.1021/ja01063a036

文献信息

• Efficient Nucleophilic Substitution of α-Aryl Alcohols with 1,3-Dicarbonyl Compounds Catalyzed by Tin Ion-Exchanged Montmorillonite
  作者：Makoto Onaka、Jiacheng Wang、Yoichi Masui

  DOI：10.1055/s-0030-1258567

  日期：2010.10

  Tin ion-exchanged montmorillonite demonstrated the high catalytic activity for the direct nucleophilic substitution of a hydroxyl group in α-aryl alcohols with various 1,3-dicarbonyl compounds including less acidic 1,3-diesters in crude solvents to afford the benzylated products accompanied by water.

  锡离子交换蒙脱石表现出对α-芳基醇中的羟基与各种1,3-双羰基化合物（包括酸性较弱的1,3-双酯）在粗溶剂中进行直接亲核取代反应的高催化活性，生成伴有水的苄基化产物。
• Holmberg, Acta Academiae Aboensis, Series B: Mathematica et Physica, 1949, vol. 16, # 6, p. 72
  作者：Holmberg

  DOI：——

  日期：——
• Ring-substituted histaprodifen analogues as partial agonists for histamine H1 receptors: synthesis and structure–activity relationships
  作者：S Elz

  DOI：10.1016/s0223-5234(00)00105-7

  日期：2000.1

  Thirteen racemic benzene ring-substituted analogues of histaprodifen (8a; 2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine), a novel lead for potent and selective histamine H-1-receptor agonists, have been prepared from substituted 4,4-diphenylbutyronitriles 5 via cyclization of the corresponding methyl butyrimidates 6 with 2-oxo-4-phthalimido-1-butyl acetate in liquid ammonia, followed by deprotection. Nitriles 5 were accessible by alkylation of either substituted diphenylmethanes with 3-bromopropionitrile or diethyl malonate with substituted 1-chloro-diphenylmethanes and subsequent standard reactions. The title compounds 8 displayed partial agonism on contractile H-1 receptors of the guinea-pig ileum (E-max = 2-98% relative to histamine) and, compared with the endogenous agonist, were endowed with agonist potencies of 4-92%. The meta fluorinated (gc) and meta chlorinated (8f) analogues showed the highest relative potency in this series (95% confidence Limits 85-99% and 78-102%), but did not exceed the value of the lead 8a (99-124%). Compound 8c (2-[2-[3-(3-fluorophenyl)-3-phenylpropyl]-1H-imidazol-4-yl]ethanamine) was a partial agonist at contractile H-1 receptors of the guinea-pig aorta (relative potency 154% vs. 100% for histamine) and at relaxation-mediating endothelial H-1 receptors of the rat aorta (relative potency 556% vs. 100% for histamine) and matched with the functional behaviour of 8a. Agonism observed for each compound was sensitive to blockade by the selective H-1-receptor antagonist mepyramine (pA(2) approximate to 9 (guinea-pig) and pA(2) approximate to 8 (rat aorta)). All histaprodifen analogues 8 stimulated neither histaminergic H-2/H-3, nor cholinergic M-3 receptors. They displayed only low to moderate affinity for these sites (H-2: pD'(2), < 5; H-3/M-3: pA(2) < 6). With regard to the substitution pattern on the benzene ring, there was no correlation between the histaprodifen series and the corresponding derivatives of another selective H-1-receptor agonist, viz. 2-phenylhistamine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
• The Synthesis and Ionization Constants of the Six Aminobenzo [<i>c</i>]phenanthrenes
  作者：Melvin S. Newman、Jochanan. Blum

  DOI：10.1021/ja01063a036

  日期：1964.5.5