(4-羟基-1-甲基-4-苯基-3-哌啶基)苯基甲酮 | 5409-66-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (4-羟基-1-甲基-4-苯基-3-哌啶基)苯基甲酮
• 中文别名: 氟西汀杂质31
• 英文名称: 3-benzoyl-4-hydroxy-1-methyl-4-phenylpiperidine
• 英文别名: 4-hydroxy-1-methyl-4-phenylpiperidin-3-yl(phenyl)methanone；1-methyl-3-benzoyl-4-hydroxy-4-phenylpiperidine；3-benzoyl-1-methyl-4-phenyl-γ-piperidol；3-benzoyl-4-hydroxy-1-methyl-4-phenylpiperidol；(4-hydroxy-1-methyl-4-phenyl-piperidin-3-yl)-phenyl-methanone；(4-hydroxy-1-methyl-4-phenyl-[3]piperidyl)-phenyl ketone；(4-hydroxy-1-methyl-4-phenylpiperidin-3-yl)-phenylmethanone
• CAS: 5409-66-5
• 化学式: C₁₉H₂₁NO₂
• mdl: MFCD00086343
• 分子量: 295.381
• InChiKey: TVRFABREAYQAQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  (4-羟基-1-甲基-4-苯基-3-哌啶基)苯基甲酮 在 硫酸 作用下， 生成 2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine
  参考文献：
  名称：

  PYRIDINDENE DERIVATIVES. I

  摘要：

  DOI：

  10.1021/jo01147a032
• 作为产物：
  描述：

  N-methyl-3-oxo-N-(3-oxo-3-phenylpropyl)-3-phenylpropan-1-aminium chloride 在 sodium hydroxide 作用下， 以 水 为溶剂， 以10.43 g的产率得到(4-羟基-1-甲基-4-苯基-3-哌啶基)苯基甲酮
  参考文献：
  名称：

  Gul, Halise Inci; Calis, Unsal; Vepsalainen, Jouko, Arzneimittel-Forschung/Drug Research, 2002, vol. 52, # 12, p. 863 - 869

  摘要：

  DOI：

文献信息

• Exploration of Piperidinols as Potential Antitubercular Agents
  作者：Areej Abuhammad、Elizabeth Fullam、Sanjib Bhakta、Angela Russell、Garrett Morris、Paul Finn、Edith Sim

  DOI：10.3390/molecules191016274

  日期：——

  Novel drugs to treat tuberculosis are required and the identification of potential targets is important. Piperidinols have been identified as potential antimycobacterial agents (MIC < 5 μg/mL), which also inhibit mycobacterial arylamine N-acetyltransferase (NAT), an enzyme essential for mycobacterial survival inside macrophages. The NAT inhibition involves a prodrug-like mechanism in which activation leads to the formation of bioactive phenyl vinyl ketone (PVK). The PVK fragment selectively forms an adduct with the cysteine residue in the active site. Time dependent inhibition of the NAT enzyme from Mycobacterium marinum (M. marinum) demonstrates a covalent binding mechanism for all inhibitory piperidinol analogues. The structure activity relationship highlights the importance of halide substitution on the piperidinol benzene ring. The structures of the NAT enzymes from M. marinum and M. tuberculosis, although 74% identical, have different residues in their active site clefts and allow the effects of amino acid substitutions to be assessed in understanding inhibitory potency. In addition, we have used the piperidinol 3-dimensional shape and electrostatic properties to identify two additional distinct chemical scaffolds as inhibitors of NAT. While one of the scaffolds has anti-tubercular activity, both inhibit NAT but through a non-covalent mechanism.

  治疗结核病需要新型药物，而确定潜在靶点非常重要。哌啶醇已被确定为潜在的抗结核药（MIC < 5 μg/mL），它还能抑制分枝杆菌的芳胺 N-乙酰转移酶（NAT），这是分枝杆菌在巨噬细胞内生存所必需的一种酶。对 NAT 的抑制涉及一种类似原药的机制，激活后会形成具有生物活性的苯基乙烯基酮（PVK）。PVK 片段选择性地与活性位点的半胱氨酸残基形成加合物。对海洋分枝杆菌（M. marinum）NAT 酶的时间依赖性抑制表明，所有抑制性哌啶醇类似物都具有共价结合机制。这种结构活性关系突出了哌啶醇苯环上卤化物取代的重要性。来自M.marinum和M.tuberculosis的NAT酶的结构虽然有74%相同，但其活性位点裂隙中的残基不同，因此可以评估氨基酸取代对了解抑制效力的影响。此外，我们还利用哌啶醇的三维形状和静电特性确定了另外两种作为 NAT 抑制剂的不同化学支架。虽然其中一种化学支架具有抗结核活性，但这两种化学支架都能通过非共价机制抑制 NAT。
• Uncommon expansion of piperidine ring into hydroazocine ring in reactions of some piperidine β-acyl derivatives with acetylenecarboxylic acids esters
  作者：A. V. Malkova、K. B. Polyanskii、A. T. Soldatenkov、S. A. Soldatova、N. L. Merkulova、V. N. Khrustalev

  DOI：10.1134/s107042801602010x

  日期：2016.2

  Cyclohexanone condensation with formaldehyde and methylamine led to the formation of 4ahydroxy-2-methyloctahydrospiro[isoquinoline-4,1'-cyclohexan]-2'-one whose structure was established by means of X-ray diffraction (XRD) analysis. This spiro compound reacted with acetylenecarboxylic acids esters with unexpected conversion of its piperidine ring into a hexahydroazocine cycle. The uncommon expansion

  环己酮与甲醛和甲胺的缩合导致形成4ahydroxy-2-methyloctahydrospiro [isoquinoline-4,1'-cyclohexan] -2'-one，其结构通过X射线衍射（XRD）分析确定。该螺环化合物与乙炔基羧酸酯反应，其哌啶环意外地转化为六氢偶氮嗪循环。通过将4-羟基-1-甲基-4-苯基哌啶-3-基（苯基）甲酮在用甲基处理后类似地转化为偶氮辛衍生物，证实了β-酰基取代的哌啶环向六氢偶氮丙稀环的罕见膨胀反应。丙酸。
• Cascade Synthesis of 2-Azafluorene, Azocine, and Azabicyclononane Derivatives by Reaction of Activated Acetylenes with Some β-Amino Ketones
  作者：S. A. Soldatova、N. M. Kolyadina、A. T. Soldatenkov、A. V. Malkova

  DOI：10.1134/s1070428019040109

  日期：2019.4

  followed by domino process, leading to the formation of dimethyl 2-methyl-1,2-dihydro-9H-indeno[2,1-c]-pyridine-3,4-dicarboxylate. The reaction of the same Mannich base with methyl propiolate involves 1,3-sigma-tropic rearrangement with neutralization of the positive charge on the nitrogen atom in the intermediate structure and negative charge transfer to the carbonyl oxygen atom. Next follows aldo

  从α-茚满酮和α-四氢萘酮获得的双曼尼希碱含有一个双-β-氨基酮片段，是通过与乙炔二羧酸二甲酯和丙酸甲酯二甲酯反应合成氮杂环的有前途的中间体化合物。这些反应的产物由活化的乙炔结构确定。该反应开始于活化的炔属化合物攻击曼尼希碱的叔氮原子上，得到1，3-两性离子中间体。随后的多米诺骨牌反应是通过形成和/或断裂几个C-C键来中和氮原子上的电荷而驱动的。1的负电荷中心的分子内攻击H-茚并[2,1 - c ]吡啶-3,4-二羧酸酯。相同的曼尼希碱与丙酸甲酯的反应涉及1,3-sigma-tropic重排，中和中间结构中氮原子上的正电荷，并将负电荷转移至羰基氧原子。接下来用第二个β-氨基羰基片段进行羟醛缩合/巴豆化以产生甲基2'-甲基-1-氧代-1,1'，2'，3,5'，11'-六氢螺-[茚2,6' -indeno [2.1- c[偶氮]]-4'-羧酸盐。高效液相色谱/质谱法揭示了通过分子内质子从1,3
• Identification of the anti-mycobacterial functional properties of piperidinol derivatives
  作者：Collette S Guy、Esther Tichauer、Gemma L Kay、Daniel J Phillips、Trisha L Bailey、James Harrison、Christopher M Furze、Andrew D Millard、Matthew I Gibson、Mark J Pallen、Elizabeth Fullam

  DOI：10.1111/bph.13744

  日期：2017.7

  mycobacteria and rapidly kill this organism with a cytotoxicity selectivity index for mycobacteria of >30-fold. Whole genome sequencing of M. smegmatis strains resistant to the lead compounds led to the identification of a number of single nucleotide polymorphisms indicating multiple targets. CONCLUSION AND IMPLICATIONS Our results indicate that the piperidinol moiety represents an attractive compound class

  背景和目的结核病（TB）仍然是全球主要的健康威胁，目前是全球单一传染源导致死亡的主要原因。目前的结核病药物治疗方案不足，迫切需要新的抗结核药物才能成功对抗日益流行的耐药结核病。本研究的目的是研究一种对结核杆菌具有高度活性的哌啶醇化合物衍生物。实验方法评估了哌啶醇化合物及其相应的双曼尼希碱类似物针对耻垢分枝杆菌和革兰氏阴性生物体的抗菌特性。进行细胞毒性研究以确定这些化合物的选择性指数。针对哌啶醇和相应的双曼尼希碱先导衍生物产生了耻垢分枝杆菌的自发抗性突变体，并采用全基因组测序来确定在这些化合物存在下导致选择压力的遗传修饰。主要结果 发现哌啶醇和双曼尼希碱类似物对分枝杆菌具有选择性，并能快速杀死该微生物，对分枝杆菌的细胞毒性选择性指数>30 倍。对先导化合物具有抗性的耻垢分枝杆菌菌株的全基因组测序导致鉴定出许多表明多个靶标的单核苷酸多态性。结论和意义我们的结果表明哌啶醇部分代表了寻找新型抗结核
• 4,4-Diarylpiperidine compositions and use
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：US04016280A1

  公开（公告）日：1977-04-05

  4,4-Diarylpiperidine compounds, preferably 4,4-diphenylpiperidine which are substituted or unsubstituted in the 1-position of the piperidine nucleus, such as 1-(lower alkyl)-4,4-diphenylpiperidines, 1-(lower alkyl)-4-phenyl-4-tolylpiperidines, and their substantially non-toxic, pharmaceutically-acceptable acid addition salts, are highly effective central nervous system (CNS) stimulants which are superior to known amphetamine-type stimulants. A novel and highly advantageous process of making such 4,4-diarylpiperidine compounds comprises reacting a 4-aryl-4-hydroxypiperidine compound which may be substituted in its 3-position by an aroyl group, with an aromatic hydrocarbon, in particular with benzene, in the presence of a Friedel-Crafts-type catalyst.

  4,4-二芳基哌啶化合物，优选4,4-二苯基哌啶，其在哌啶环的1位上取代或未取代，例如1-(较低烷基)-4,4-二苯基哌啶，1-(较低烷基)-4-苯基-4-甲基苯基哌啶，以及它们的基本无毒、药学上可接受的酸盐，是高度有效的中枢神经系统（CNS）兴奋剂，优于已知的苯丙胺类兴奋剂。制备这种4,4-二芳基哌啶化合物的一种新颖且极具优势的方法包括，在Friedel-Crafts型催化剂的存在下，将可能在其3位上被芳酰基取代的4-芳基-4-羟基哌啶化合物与芳香族碳氢化合物，特别是苯，反应。