2-(3-azidopropyl)-2-(4-fluorophenyl)[1,3]dioxolane | 660844-86-0

• 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: 2-(3-azidopropyl)-2-(4-fluorophenyl)[1,3]dioxolane
• 英文别名: 2-(3-Azidopropyl)-2-(4-fluorophenyl)-1,3-dioxolane
• CAS: 660844-86-0
• 化学式: C₁₂H₁₄FN₃O₂
• 分子量: 251.26
• InChiKey: CTBAWYZBKQKIDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3-azidopropyl)-2-(4-fluorophenyl)[1,3]dioxolane 在 三苯基膦 、 水 作用下， 以 乙醚 为溶剂， 反应 19.0h， 以95%的产率得到2-(3-aminopropyl)-2-(4-fluorophenyl)[1,3]dioxolane
  参考文献：
  名称：

  Molecular hybridization of 4-azahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecane-3-ol with sigma (σ) receptor ligands modulates off-target activity and subtype selectivity

  摘要：

  A series of N-substituted 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)] dodecan-3-ols incorporating the respective arylalkyl subunits from several known sigma (sigma) receptor ligands were synthesized and evaluated for their affinity against sigma receptors and dopamine receptors. The hybrid trishomocubane-derived ligands (4-6) showed good selectivity for sigma(1) and sigma(2) receptors over multiple dopamine receptors. The molecular hybrid obtained from haloperidol and 4-azahexacyclo[ 5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)] dodecan-3-ol (4, sigma(1) K-i = 27 nM, sigma(2) K-i = 55 nM) showed reduced affinity for D-1-D-5 dopamine receptors when compared to haloperidol itself. The compound with the greatest sigma(1) affinity in the series, benzamide 4 (sigma(1) K-i = 7.6 nM, sigma(2) K-i = 225 nM) showed a complete reversal of the subtype selectivity displayed by the highly sigma(2) selective parent benzamide, RHM-2 (3, sigma(1) K-i = 10412 nM, sigma(2) K-i = 13.3 nM). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.098
• 作为产物：
  描述：

  2-(3-氯丙基)-2-(4-氟苯基)-1,3-二氧戊烷 在 sodium azide 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以97.4%的产率得到2-(3-azidopropyl)-2-(4-fluorophenyl)[1,3]dioxolane
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species

  摘要：

  The long-term, irreversible, Parkinsonism-like side effects of haloperidol have been speculated to involve several mechanisms. More recently, it has been speculated that the metabolic transformation to MPP+-like species may contribute to the Parkinsonism-like side effects. Because BCPP+ and its reduced analogue have been shown to possess the potential to destroy dopamine receptors in the nigrostriatum, we have designed new analogues of haloperidol lacking the structural features necessary to form neurotoxic quaternary species but retaining their dopamine-binding capacity. The most potent agent at the D2 receptor, the homopiperidine analogue 11, was found to be equipotent to haloperidol. It was also of interest to identify analogues with DA binding profiles similar to that of clozapine at the dopamine receptor subtypes. Evaluation of the proposed agents shows that the ratio of D2 to D4 (2) binding of clozapine was mimicked by 7 [K-i(D2) = 33, K-i(D3) = 200, K-i(D4) = 11 nM; K-i(D2)/K-i(D4) = 3] and 9 [K-i(D2) = 44, K-i(D3) = 170, K-i(D4) = 24 nM; K-i(D2)/K-i(D4) = 2]. A preliminary in-vivo testing of compound 7 shows that its behavioral profile is similar to that of clozapine. This profile suggests that there is a need for further evaluation of these two synthetic agents and their enantiomers for efficacy and lack of catalepsy in animal models.

  DOI：

  10.1021/jm0301033