2-(3-aminopropyl)-2-(4-fluorophenyl)[1,3]dioxolane | 3308-93-8

• 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: 2-(3-aminopropyl)-2-(4-fluorophenyl)[1,3]dioxolane
• 英文别名: 4-amino-1,1-ethylenedioxy-1-(4-fluorophenyl)butane；2-(4-fluorophenyl)-2-(3-aminopropyl)-1,3-dioxolane；4-amino-1-(4-fluorophenyl)-1-butanone ethylene ketal；3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propylamine；2-(4-Fluorphenyl)-2-(3-aminopropyl)-1,3-dioxolan；2-(4-fluorophenyl)-1,3-dioxolane-2-propanamine；3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propan-1-amine
• CAS: 3308-93-8
• 化学式: C₁₂H₁₆FNO₂
• 分子量: 225.263
• InChiKey: GOCRWQKOSCUNLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-aminopropyl)-2-(4-fluorophenyl)[1,3]dioxolane 在 盐酸 、 三乙胺 作用下， 以 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 18.0h， 生成 1-[4-oxo-4-(4-fluorophenyl)butyl]-4,4-diphenyl-4-silapiperidine
  参考文献：
  名称：

  4-Silapiperidine and 4-silapiperidinium derivatives: syntheses and structural characterization

  摘要：

  A series of novel 4-silapiperidine and 4-silapiperidinium derivatives, with two silicon-bound aryl groups and various N-organyl groups, have been synthesized and structurally characterized (solution H-1, C-13, F-19, and Si-29 NMR spectroscopy; eight crystal structure analyses). These synthetic and structural investigations provide the basis for the development of novel silicon-based drugs containing, a 4-silapiperidine or 4-silapiperidinium skeleton. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2004.08.023
• 作为产物：
  描述：

  4-氯-4'-氟苯丁酮 在 sodium hydroxide 、 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 37.0h， 生成 2-(3-aminopropyl)-2-(4-fluorophenyl)[1,3]dioxolane
  参考文献：
  名称：

  取代的2-氨基四氢萘的合成及其降压性能。

  摘要：

  报道了几种自发性高血压大鼠体内几种4-（1,2,3,4-四氢萘基-2-氨基）-1-（4-氟苯基）-1-丁酮的合成和活性。最大的降压活性与氨基四氢萘部分中的5,6-二甲氧基取代有关。

  DOI：

  10.1002/jps.2600740110

文献信息

• Tropyl derivatives
  申请人：Sandoz, Inc.

  公开号：US04366154A1

  公开（公告）日：1982-12-28

  Tropyl derivatives of the formula: ##STR1## in which R.sup.1 is (a) phenyl linked through a direct bond, --O--, ##STR2## (in which m=2 or 3); (b) diphenylmethyl; or (c) 10H-phenothiazin-10-yl; (each of which type may be substituted, or unsubstituted); R.sup.2 is --H, --OH, or --O Si (CH.sub.3).sub.3 ; and R.sup.3 is substituted or unsubstituted phenyl, e.g. 4-[3-(4-fluorobenzoyl)-8-azabicyclo [3.2.1]oct-8-yl]-1-(-4-fluorophenyl)-1-butanone, in free base form or pharmaceutically acceptable acid addition salts are useful as pharmaceuticals.

  Tropyl衍生物的公式如下：##STR1## 其中R.sup.1是(a) 通过直接键连接的苯基，--O--，##STR2##（其中m=2或3）；(b) 二苯甲基；或(c) 10H-苯并噻嗪-10-基；（每种类型可能是取代的或未取代的）；R.sup.2是--H，--OH或--O Si（CH.sub.3）.sub.3；R.sup.3是取代的或未取代的苯基，例如4-[3-(4-氟苯甲酰基)-8-氮杂双环[3.2.1]辛-8-基]-1-(-4-氟苯基)-1-丁酮，在游离碱形式或药学上可接受的酸盐形式上用作药物。
• Design, Synthesis, and Evaluation of Metabolism-Based Analogues of Haloperidol Incapable of Forming MPP+-like Species
  作者：M. Lyles-Eggleston、R. Altundas、J. Xia、D. M. N. Sikazwe、P. Fan、Q. Yang、S. Li、W. Zhang、X. Zhu、A. W. Schmidt、M. Vanase-Frawley、A. Shrihkande、A. Villalobos、R. F. Borne、S. Y. Ablordeppey

  DOI：10.1021/jm0301033

  日期：2004.1.1

  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.
• 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
  作者：Samuel D. Banister、Iman A. Moussa、William T. Jorgensen、Sook Wern Chua、Michael Kassiou

  DOI：10.1016/j.bmcl.2011.04.098

  日期：2011.6

  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.
• Sila-Trifluperidol, a Silicon Analogue of the Dopamine (D₂) Receptor Antagonist Trifluperidol: Synthesis and Pharmacological Characterization
  作者：Reinhold Tacke、Binh Nguyen、Christian Burschka、W. Peter Lippert、Alexandra Hamacher、Christian Urban、Matthias U. Kassack

  DOI：10.1021/om901011t

  日期：2010.4.12

  Trifluperidol (2a) is a dopamine (1)2) receptor antagonist of the butyrophenone type. Carbon/silicon exchange (sila-substitution) in the 4-position of the piperidine ring of 2a (R3COH --> R3SiOH) results in sila-trifluperidol (2b). The silanol 21) was synthesized in a multistep synthesis, starting from triethoxy(vinyl)silane, and was isolated as the hydrochloride 2b.HCl. Compound 2b" HC1 was structurally characterized by single-crystal X-ray diffraction and solution NMR spectroscopy, and the stability of the silanol 2b in aqueous solutions at different pH values was studied by ESI-MS experiments. In addition, the pharmacological profiles of the C/Si analogues trifluperidol (2a) and sila-trifluperidol (2b) and of the related compounds haloperidol (la) and sila-haloperidol (lb) were studied in functional receptor assays at human dopamine DI and D, receptors. Sila-substitution of la ( lb) and 2a ( 2b) affects the pharmacological properties significantly.
• Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT1C-selective antagonist
  作者：Abd M. Ismaiel、Joseph De Los Angeles、Milt Teitler、Stacy Ingher、Richard A. Glennon

  DOI：10.1021/jm00069a010

  日期：1993.8

  DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5-HT1C/2 serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT1C- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT1C- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT1A serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT1C sites and (b) it has been used as a ''5-HT2-selective'' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure-affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4-fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one(26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000-fold selectivity versus 5-HT1C sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT1C-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.