地芬尼多杂质2 | 63645-18-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 地芬尼多杂质2
• 英文名称: 4-hydroxy-4,4-diphenylbutyl chloride
• 英文别名: 4-chloro-1,1-diphenyl-butan-1-ol；4-chloro-1,1-diphenyl-n-butanol；4-chloro-1,1-diphenylbutan-1-ol；α-(3-chloropropyl)-α-phenylbenzyl alcohol
• CAS: 63645-18-1
• 化学式: C₁₆H₁₇ClO
• 分子量: 260.763
• InChiKey: YGSAARYDQXFRKR-UHFFFAOYSA-N

物化性质

• 沸点：
  420.3±45.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  地芬尼多杂质2 在 吡啶 、 三氯氧磷 作用下， 以50.9%的产率得到1,1'-(4-氯-1-丁烯亚基)二苯
  参考文献：
  名称：

  Biernacki, Wladyslaw; Gdula, Andrzej, Polish Journal of Chemistry, 1981, vol. 55, # 4, p. 849 - 852

  摘要：

  DOI：
• 作为产物：
  描述：

  溴苯 、 4-氯丁酸甲酯 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 生成 地芬尼多杂质2
  参考文献：
  名称：

  Selective inhibitors of GABA uptake: synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues

  摘要：

  A series of lipophilic diaromatic derivatives of the glia-selective GABA uptake inhibitor (R)-4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol [(R)-exo-THPO, 4] were synthesized via reductive amination of 3-ethoxy-4,5,6,7-tetrahydrobenzo[d]isoxazol-4-one (9) or via N-alkylation of O-alkylatedracemic 4. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation or primary cultures of mouse cortical neurons and glia cells (astrocytes), as well as HEK cells transfected with cloned mouse GABA transporter subtypes (GAT1-4). The activity against isoniazid-induced convulsions in mice after subcutaneous administration of the compounds was determined. All of the compounds were potent inhibitors of synaptosomal uptake the most potent compound being (RS)-4-[N-(1,1-diphenylbut-1-4-en-yl)amino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (17a, IC50 = 0.14 muM). The majority of the compounds showed a weak preference for glial, as compared to neuronal, GABA uptake. The highest degree of selectivity was 10-fold corresponding to the glia selectivity of (R)-N-methyl-exo-THPO (5). All derivatives showed a preference for the GAT1 transporter, as compared with GAT2-4, with the exception of (RS)-4-[N-[1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (28d), which quite surprisingly turned out to be more potent than GABA at both GAT1 and GAT2 subtypes. The GAT1 activity was shown to reside in (R)-28d whereas (R)-28d and (S)-28d contributed equally to GAT2 activity. This makes (S)-28d a GAT2 selective compound, and (R)-28d equally effective in inhibition of GAT1 and GAT2 mediated GABA transport. All compounds tested were effective as anticonvulsant reflecting that these compounds have blood-brain barrier permeating ability. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.029

文献信息

• 4-aminotetrahydrobenzisoxazole or -isothiazole compounds
  申请人：H. Lundbeck A/S

  公开号：US05998613A1

  公开（公告）日：1999-12-07

  The present invention relates to novel 4-aminotetrahydrobenzisoxazoles or 4-aminotetrahydrobenziothiazoles having gamma-aminobutanoic acid (GABA)-uptake inhibiting activity and thus useful in the treatment of analgesia, psychosis, convulsions, anxiety, epileptic disorders or muscular and movement disorders, such as spastic disorders or symptoms in Huntington's disease or Parkinson disease.

  本发明涉及具有γ-氨基丁酸（GABA）摄取抑制活性的新型4-氨基四氢苯并异噁唑或4-氨基四氢苯并噻唑，因此在治疗疼痛、精神病、抽搐、焦虑、癫痫性疾病或肌肉和运动障碍方面具有用处，如在亨廷顿病或帕金森病中的痉挛障碍或症状。
• The formation of all-cis-(multi)fluorinated piperidines by a dearomatization–hydrogenation process
  作者：Zackaria Nairoukh、Marco Wollenburg、Christoph Schlepphorst、Klaus Bergander、Frank Glorius

  DOI：10.1038/s41557-018-0197-2

  日期：2019.3

  rhodium-catalysed dearomatization–hydrogenation of fluoropyridine precursors. This strategy enables the formation of a plethora of substituted all-cis-(multi)fluorinated piperidines in a highly diastereoselective fashion through pyridine dearomatization followed by complete saturation of the resulting intermediates by hydrogenation. Fluorinated piperidines with defined axial/equatorial orientation of fluorine

  哌啶和氟取代基都是药物、农用化学品和材料中独立不可缺少的成分。因此，从逻辑上讲，将氟原子掺入哌啶支架是一个具有巨大潜力的领域。然而，形成这些架构的综合方法通常是不切实际的。取代的单氟化哌啶的非对映选择性合成通常需要具有预定立体化学的底物。多氟化哌啶的研究更具挑战性，通常需要在多步合成中进行。在本报告中，我们描述了一锅铑催化的氟吡啶前体脱芳构化加氢的简单过程。这种策略能够形成大量取代的全顺式-（多）氟化哌啶以高度非对映选择性方式通过吡啶脱芳构化，然后通过氢化使所得中间体完全饱和。具有确定的氟取代基轴向/赤道取向的氟化哌啶已成功应用于商业药物类似物的制备。此外，通过这种脱芳构化-加氢过程获得了氟化 PipPhos 以及氟化离子液体。
• Cis-2,6-dimethyl-.alpha.,.alpha.-diphenyl-1-piperidinebutanol compounds
  申请人：Parke, Davis & Company

  公开号：US04031101A1

  公开（公告）日：1977-06-21

  cis-2,6-Dimethyl-.alpha.,.alpha.-diphenyl-1-piperidinebutanol; and acid-addition salts. The compounds are pharmacological agents, especially antiarrythmic agents. The compounds can be produced by reacting phenyl lithium or phenylmagnesium halide with cis-.gamma.-(2,6-dimethylpiperidino)butyrophenone or a lower alkyl ester of cis-2,6-dimethyl-1-piperidinebutyric acid; by reacting .alpha.-(3-halopropyl)-.alpha.-phenylbenzyl alcohol with cis-2,6-dimethylpiperidine, or by reacting cis-1- (3-lithiopropyl)-2,6-dimethylpiperidine with benzophenone.

  cis-2,6-二甲基-α,α-二苯基-1-哌啶丁醇；及其酸盐。这些化合物是药理学试剂，特别是抗心律失常试剂。这些化合物可以通过将苯基锂或苯基镁卤化物与顺式-γ-(2,6-二甲基哌啶基)丁酰苯酮或顺式-2,6-二甲基-1-哌啶丁酸的较低烷基酯反应而制备；通过将α-(3-卤代丙基)-α-苯基苄醇与顺式-2,6-二甲基哌啶反应，或通过将顺式-1-(3-锂代丙基)-2,6-二甲基哌啶与苯甲酮反应制备。
• One-pot synthesis of diarylalkylcarbinols and substituted derivatives through carbon monoxide insertion reactions into aryllithiums
  作者：Arturo A. Vitale、F. Doctorovich、N. Sbarbati Nudelman

  DOI：10.1016/0022-328x(87)85117-3

  日期：1987.9

  atmospheric pressure and −78°C, affords diarylalkylcarbinols in good yields. Alkyl chlorides do not react under similar experimental conditions. This feature makes the reaction particularly useful for the synthesis of alcohols functionalized in the alkyl chain through subsequent reactions of the diaryl(chloro)alkylcarbinols. The procedure can also be adapted to afford substituted cyclic ethers. If the reaction

  在烷基溴化物RBr存在下，芳基锂的THF溶液（芳基= Ph，邻茴香基）的羰基化反应；在大气压和-78℃下，以良好的收率得到二芳基烷基甲醇。烷基氯在相似的实验条件下不会发生反应。该特征使得该反应对于通过二芳基（氯）烷基羰基醇的后续反应来合成在烷基链上官能化的醇特别有用。该方法也可以适用于提供取代的环醚。如果该反应在二溴代烷烃的存在下进行，则只有一个溴原子反应，得到有用的合成中间体二芳基（溴代）烷基甲醇。用仲和叔烷基溴化物以可变的产率得到二芳基烷基醚。
• Diphenidol-related diamines as novel muscarinic M4 receptor antagonists
  作者：Lucilla Varoli、Aldo Andreani、Silvia Burnelli、Massimiliano Granaiola、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Andrea Bedini、Nicola Fazio、Santi Spampinato

  DOI：10.1016/j.bmcl.2008.03.061

  日期：2008.5

  of diphenidol have been synthesized and characterized in receptor binding and cellular functional assays versus human muscarinic M(1)-M(5) receptors expressed in CHO cells. Compound 8b, a methiodide derivative with a bipiperidinyl moiety and a second diphenidol framework, showed a potent and selective M(4) activity as competitive antagonist. Moreover 8b, acting as an allosteric modulator, was able

  苯甲酚的一系列盐酸盐衍生物2a-9a和季铵衍生物3b-9b已合成，并在受体结合和细胞功能测定中相对于在CHO细胞中表达的人毒蕈碱M（1）-M（5）受体进行了表征。化合物8b，一种具有联哌啶基部分和第二个苯二酚骨架的甲硫醚衍生物，显示出有效和选择性的M（4）活性，可作为竞争性拮抗剂。此外8b，作为一种变构调节剂，能够阻止[（3）H] -N-甲基东pol碱从暴露于阿托品的CHO-M（4）细胞膜的解离速率。综上所述，这些数据表明8b可能为发现毒蕈碱受体的新型多价拮抗剂开辟新途径。