4-chloromethyl-2-naphthalen-1-yl[1,3]dioxolane

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-chloromethyl-2-naphthalen-1-yl[1,3]dioxolane
• 英文别名: 4-(Chloromethyl)-2-naphthalen-1-yl-1,3-dioxolane
• 化学式: C₁₄H₁₃ClO₂
• 分子量: 248.709
• InChiKey: XRZUAUBRDVSSIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 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-chloromethyl-2-naphthalen-1-yl[1,3]dioxolane 在 potassium iodide 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 N-((2-(naphthalen-1-yl)-1,3-dioxolan-4-yl)methyl)propan-2-ammonium hydrogenoxalate
  参考文献：
  名称：

  Effect of the rigidification of propranolol, a mixed β-adrenoceptor and 5-HT1AR antagonist

  摘要：

  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。

  DOI：

  10.1691/ph.2019.8878
• 作为产物：
  描述：

  1-萘甲醛 、 3-氯-1,2-丙二醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 以65%的产率得到4-chloromethyl-2-naphthalen-1-yl[1,3]dioxolane
  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

文献信息

• 1,3-Dioxolane-Based Ligands as a Novel Class of α₁-Adrenoceptor Antagonists
  作者：Livio Brasili、Claudia Sorbi、Silvia Franchini、Massimo Manicardi、Piero Angeli、Gabriella Marucci、Amedeo Leonardi、Elena Poggesi

  DOI：10.1021/jm021078o

  日期：2003.4.1

  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.
• 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。