3-(3-chlorophenyl)-3-phenylpropanoic acid | 21998-29-8

• 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: 3-(3-chlorophenyl)-3-phenylpropanoic acid
• CAS: 21998-29-8
• 化学式: C₁₅H₁₃ClO₂
• 分子量: 260.72
• InChiKey: YGWFEBLGVWKAGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  3-(3-chlorophenyl)-3-phenylpropanoic acid 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 氯化亚砜 、 氨 、 potassium iodide 作用下， 以 乙醚 、 二氯甲烷 、 二甲基亚砜 为溶剂， -30.0~95.0 ℃ 、2.6 MPa 条件下， 反应 191.0h， 生成 2-[2-[2-[3-(3-chlorophenyl)-3-phenylpropyl]-1H-imidazol-5-yl]ethyl]isoindole-1,3-dione
  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：

  1-氯-3-(氯苯基甲基)苯 在 氢氧化钾 、 sodium hydride 、 sodium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.17h， 生成 3-(3-chlorophenyl)-3-phenylpropanoic acid
  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

文献信息

• Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids
  作者：Rui Liu、Zhenyu Yang、Yuxin Ni、Kaixuan Song、Kai Shen、Shaohui Lin、Qinmin Pan

  DOI：10.1021/acs.joc.7b01248

  日期：2017.8.4

  Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids (including β,β-disubstituted acrylic acids) was developed and optimized, which provided a mild and convenient method for the highly challenging synthesis of β-quaternary carbons substituted carboxylic acids.

  开发并优化了Pd（II）/联吡啶催化的芳基硼酸向α，β-不饱和羧酸（包括β，β-二取代的丙烯酸）的共轭加成反应，为高难度的β合成提供了温和而便捷的方法-季碳取代的羧酸。
• Cationic Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids in aqueous media
  作者：Yuxin Ni、Kaixuan Song、Kai Shen、Zhenyu Yang、Rui Liu、Shaohui Lin、Qinmin Pan

  DOI：10.1016/j.tetlet.2018.02.013

  日期：2018.3

  An in-situ generated cationic Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids in water was developed and optimized. For most substrates, nearly quantitative yields were given, and the products can be purified by simple washing without column chromatography. The reaction can be scaled up to 1.0 g easily with excellent yields. Also the loading of

  开发并优化了芳基硼酸到水中α，β-不饱和羧酸的阳离子Pd（II）/联吡啶催化的阳离子共轭加成反应。对于大多数底物，给出了接近定量的收率，并且可以通过不经柱色谱的简单洗涤来纯化产物。可以轻松地将反应放大至1.0 g，并具有优异的收率。同样，催化剂的载量可以以适中的产率降低到1.0mol％，并且该反应提供了温和且容易的合成β-二取代的羧酸的方法。
• Covalent organic framework supported Pd(II)‐catalyzed conjugate additions of arylboronic acids to α,β‐unsaturated carboxylic acids
  作者：Min Wen、Shujuan Lu、Chaogang Fan、Kai Shen、Shaohui Lin、Qinmin Pan

  DOI：10.1002/aoc.6263

  日期：2021.8

  A palladium(II)-coordinated covalent organic framework (Pd(II)@COF) was mechanochemically synthesized from [2,2′-bipyridine]-5,5′-diamine (Bpy) and 1,3,5-triformylphloroglucinol (Tp), which was demonstrated as a catalyst for conjugate addition of arylboronic acids to unreactive α,β-unsaturated carboxylic acids in aqueous media (water/acetone = 1:1). Modest to good yields were obtained for most substrates

  由[2,2'-联吡啶]-5,5'-二胺（Bpy）和1,3,5-三甲酰基间苯三酚（Tp）机械化学合成钯（II）配位的共价有机骨架（Pd（II）@COF） )，它被证明是芳基硼酸与非反应性 α,β-不饱和羧酸在水性介质 (水/丙酮 = 1:1) 中共轭加成的催化剂。大多数底物获得了中等至良好的产率，对催化剂可回收性的研究表明，多相催化剂在前 4 个循环中的产率大于 80%。这项研究拓宽了 COF 支持的催化的应用，并为 Pd(II) 催化提供了新的选择。
• [EN] NEW DIFLUOROKETAMIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE DIFLUOROCÉTAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2016180751A1

  公开（公告）日：2016-11-17

  The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as described herein, compositions including the compounds and methods of using the compounds.

  该发明提供了具有一般化学式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8和R9如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• 3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake
  作者：Klaus P. Bogeso、A. Vibeke Christensen、John Hyttel、Tommy Liljefors

  DOI：10.1021/jm00150a012

  日期：1985.12

  3-phenyl-1-indanamines was synthesized and tested for potential antidepressant activity and for inhibition of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) uptake. Trans isomers were generally potent inhibitors of DA, NE, and 5-HT uptake, while cis isomers preferentially inhibited the uptake of 5-HT. The affinity for the DA-uptake site was very dependent on the aromatic substitution pattern

  合成了一系列3-苯基-1-茚满胺，并测试了其潜在的抗抑郁活性以及对多巴胺（DA），去甲肾上腺素（NE）和5-羟色胺（5-HT）吸收的抑制作用。反式异构体通常是DA，NE和5-HT吸收的有效抑制剂，而顺式异构体则优先抑制5-HT的吸收。对DA吸收位点的亲和力非常取决于芳族取代模式，其中3'，4'-二氯取代的化合物的效价最高（45）。这种取代模式也导致了对NE和5-HT摄取位点的高度亲和力，但是用其他取代模式也可以获得强大的5-HT摄取抑制活性。在5-HT摄取部位只能容纳少量胺，而在DA和NE摄取部位都可以容纳较大的胺（例如哌嗪）。观察到的构效关系是根据反式（45）和顺式（72）异构体分别与5-HT和DA重叠的结果解释的，与拟议的摄取抑制剂在摄取时的三点结合有关网站。最后，比较了3-苯基-1-茚满胺与其他新型双环儿茶酚胺和/或5-羟色胺摄取抑制剂的结构，发现它们对有效抑制DA-，NE-和/或5-HT摄取具有重要意义。