4-Chlormethyl-2,2-diphenyl-dioxolan | 22195-38-6

• 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-Chlormethyl-2,2-diphenyl-dioxolan
• 英文别名: 4-(Chloromethyl)-2,2-diphenyl-1,3-dioxolane
• CAS: 22195-38-6
• 化学式: C₁₆H₁₅ClO₂
• 分子量: 274.747
• InChiKey: MTGKBVQFXBOSCH-UHFFFAOYSA-N

物化性质

• 沸点：
  390.8±37.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Chlormethyl-2,2-diphenyl-dioxolan 在 吡啶 、 lithium aluminium tetrahydride 、 potassium iodide 作用下， 以 四氢呋喃 、 氯仿 、 乙二醇甲醚 为溶剂， 反应 41.0h， 生成 (2,2-diphenyl[1,3]dioxolan-4-ylmethyl)methyl(2-phenoxyethyl)amine
  参考文献：
  名称：

  1,3-Dioxolane-Based Ligands as a Novel Class of α₁-Adrenoceptor Antagonists

  摘要：

  1,3-Dioxolane-based compounds (2-14) were synthesized, and the pharmacological profiles at alpha(1)-adrenoceptor subtypes were assessed by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)). Compound 9, with a pA(2) of 7.53, 7.36, and 8.65 at alpha(1A), alpha(1B), and alpha(1D)), respectively, is the most potent antagonist of the series, while compound 10 with a pA(2) of 8.37 at alpha(1D) subtype and selectivity ratios of 162 (alpha(1D)/alpha(1A)) and 324 (alpha(1D))/alpha(1B)) is the most selective. Binding assays in CHO cell membranes expressing human cloned alpha(1)-adrenoceptor subtypes confirm the pharmacological profiles derived from functional experiments, although the selectivity values are somewhat lower. Therefore, it is concluded that 1,3-dioxolane-based ligands are a new class of alpha(1)-adrenoceptor antagonists.

  DOI：

  10.1021/jm021078o
• 作为产物：
  描述：

  二苯甲酮 、 3-氯-1,2-丙二醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 以100%的产率得到4-Chlormethyl-2,2-diphenyl-dioxolan
  参考文献：
  名称：

  侦查新的西格玛受体配体：基于1，3-二氧戊环的结构和衍生物的合成，药理学评估和分子建模

  摘要：

  本文中，我们报告了通过将不同的取代五元杂环与适当的σR药效学胺结合而获得的新sigma受体（σR）配体的合成和生物学活性。在豚鼠脑膜上进行的放射性配体结合测定法确定了25b（1-（1,4-dioxaspiro [4.5] decan-2-ylmethyl）-4-苄基哌嗪）是该系列中最有趣的化合物，显示出高亲和力和选择性为σ 1个R（的pK我σ 1  = 9.13;σ 1 /σ 2  = 47）。在体内评估了25b调节κ激动剂（-）-U-50,488H和μ激动剂吗啡的镇痛作用的能力通过辐射热甩尾测试。它显示出在两个κ和μ受体介导的镇痛的抗阿片作用，这表明在σ激动行为1 R.对接研究的理论σ进行1 - [R同源模型。目前的工作表示用于更有效和选择性σ的设计一个新的起点1 - [R配体。

  DOI：

  10.1016/j.ejmech.2016.01.059

文献信息

• Effect of the rigidification of propranolol, a mixed β-adrenoceptor and 5-HT1AR antagonist
  作者：Franchini、Sorbi、Linciano、Brasili、Tait

  DOI：10.1691/ph.2019.8878

  日期：——

  Propranolol is a popular β adrenergic antagonists that, together with pindolol, binds also to serotoninergic receptors, namely 5-HT1A/B. In this work the rigidification of the propranolol structure by locking its hydroxyl group within a 1,3-dioxolane ring was investigated. Constrained derivatives of propranolol were synthesized, fully characterized and tested for their affinity at β-adrenoreceptors and 5-HT1A/B/C receptors using radioligand binding assay. The constrained derivatives were inactive, as expected, at β1/2/3 adrenergic receptors. Although less expected, these derivatives failed to bind also to 5-HT1A/B/C receptors. The rigidification of propranolol is detrimental for 5-HT1AR activity.

  普萘洛尔是一种常用的β肾上腺素能拮抗剂，它与吲哚洛尔一起也能与血清素能受体（即 5-HT1A/B）结合。这项研究通过将普萘洛尔结构中的羟基锁定在一个 1,3- 二氧戊环上，对其结构的刚性进行了研究。研究人员合成了普萘洛尔的受限衍生物，对其进行了全面表征，并利用放射性配体结合试验测试了它们与 β 肾上腺素受体和 5-HT1A/B/C 受体的亲和力。正如预期的那样，受约束的衍生物在 β1/2/3 肾上腺素受体上没有活性。这些衍生物也未能与 5-HT1A/B/C 受体结合，但这并不符合预期。普萘洛尔的僵化不利于 5-HT1AR 的活性。
• Orth, Angewandte Chemie, 1952, vol. 64, p. 544,547
  作者：Orth

  DOI：——

  日期：——
• Enzymatic resolution of 2,2-disubstituted-1,3-dioxolane-4-methanol carboxylic esters
  作者：Vassilia Partali、Alf Glein Melbye、Thor Alvik、Thorleif Anthonsen

  DOI：10.1016/s0957-4166(00)82313-7

  日期：——

  The enantioselectivity of enzymatic hydrolysis of carboxylic esters of various 1,2-ketals of glycerol has been investigated. The influence of the ketal group has been studied. A number of lipases and proteinases have been tested and the best enantioselectivity was obtained with proteinase from Aspergillus oryzae which gave an E-value of 9 with 2,2-dimethyl-1,3-dioxolane-4-methanol butanoate. Variations in the acyl part revealed that butanoyl was optimal. All hydrolysis products have been synthesised in homochiral forms from homochiral starting materials.
• Discovery of a new series of 5-HT1A receptor agonists
  作者：Silvia Franchini、Adolfo Prandi、Claudia Sorbi、Annalisa Tait、Annamaria Baraldi、Piero Angeli、Michela Buccioni、Antonio Cilia、Elena Poggesi、Paola Fossa、Livio Brasili

  DOI：10.1016/j.bmcl.2010.01.030

  日期：2010.3

  Starting from compounds previously identified as alpha(1)-adrenoceptor antagonists that were also found to bind to the 5-HT1A receptor, in an attempt to separate the two activities, a new series of 5-HT1A receptor agonists was identified and shown to have high potency and/or high selectivity. Of these, compound 13, which combines high selectivity (5-HT1A/alpha(1) = 151) and good agonist potency (pD(2) = 7.82; E-max = 76), was found to be the most interesting. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and structure—activity relationship studies in a series of 2-substituted 1,3-dioxolanes modified at the cationic head
  作者：P. Angeli、L. Brasili、M.L. Cingolani、G. Marucci、A. Piergentili、M. Pigini、W. Quaglia

  DOI：10.1016/s0968-0896(97)00017-5

  日期：1997.4

  To develop ligands that may be useful in exploring muscarinic receptor heterogeneity, we synthesized a series of analogues of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine oxalate and methiodide bearing a modified cationic head. These compounds, when tested on tissues containing the three subtypes M-1, M-2, and M-3, behaved as muscarinic antagonists whose results showed that different substituents on the quaternary and tertiary nitrogen affect affinity and selectivity in different ways. In particular, comparison of the affinities of these ligands with those of the reference compounds points out that compounds bearing an ethyl substituent improve the affinity of the molecule at the three subtypes, while compounds bearing a phenethyl substituent are more selective for the M-3 sites. (C) 1997 Published by Elsevier Science Ltd.