2-(4-甲基哌嗪-1-基)-1-苯基乙醇 | 5408-15-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-(4-甲基哌嗪-1-基)-1-苯基乙醇
• 英文名称: 2-(4-methylpiperazin-1-yl)-1-phenylethan-1-ol
• 英文别名: 2-(4-methyl-piperazin-1-yl)-1-phenyl-ethanol；2-(4-methyl-piperazino)-1-phenyl-ethanol；2-(4-Methyl-piperazino)-1-phenyl-aethanol；Phenyl-N--methyl-carbinol；2-(4-Methylpiperazino)-1-phenylaethanol；2-(4-methylpiperazin-1-yl)-1-phenylethanol
• CAS: 5408-15-1
• 化学式: C₁₃H₂₀N₂O
• mdl: MFCD01117937
• 分子量: 220.315
• InChiKey: IPLZBLLGRUFZGL-UHFFFAOYSA-N

物化性质

• 熔点：
  95-96 °C(Solv: hexane (110-54-3))
• 沸点：
  348.1±32.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-甲基哌嗪-1-基)-1-苯基乙醇 在 盐酸 、 Yarovenko reagent 作用下， 生成 1-(2-Fluoro-2-phenyl-ethyl)-4-methyl-piperazine; hydrochloride
  参考文献：
  名称：

  Charlon; Luu-Duc; Huguet, Farmaco, Edizione Scientifica, 1986, vol. 41, # 8, p. 586 - 596

  摘要：

  DOI：
• 作为产物：
  描述：

  2-溴苯乙酮 在 sodium tetrahydroborate 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 2.0h， 生成 2-(4-甲基哌嗪-1-基)-1-苯基乙醇
  参考文献：
  名称：

  Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson’s Disease Treatment

  摘要：

  UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating 1, enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SYSY cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SYSY cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.

  DOI：

  10.1021/acs.jmedchem.7b01575

文献信息

• [EN] SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS SUBSTITUÉS DE PYRAZOLO[1,5-A]PYRIDINES COMME INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2017011776A1

  公开（公告）日：2017-01-19

  Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供了一般式I的化合物及其立体异构体和药用可接受的盐或溶剂，其中A、B、D、E、X1、X2、X3和X4的含义如规范中所述，这些化合物是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括由RET激酶介导的疾病或紊乱。
• Prodrugs of Pyrazolo[3,4-<i>d</i>]pyrimidines: From Library Synthesis to Evaluation as Potential Anticancer Agents in an Orthotopic Glioblastoma Model
  作者：Giulia Vignaroli、Giulia Iovenitti、Claudio Zamperini、Federica Coniglio、Pierpaolo Calandro、Alessio Molinari、Anna Lucia Fallacara、Andrea Sartucci、Alessia Calgani、David Colecchia、Andrea Mancini、Claudio Festuccia、Elena Dreassi、Massimo Valoti、Francesca Musumeci、Mario Chiariello、Adriano Angelucci、Maurizio Botta、Silvia Schenone

  DOI：10.1021/acs.jmedchem.7b00637

  日期：2017.7.27

  Pyrazolo[3,4-d]pyrimidines are potent protein kinase inhibitors with promising antitumor activity but suboptimal aqueous solubility, consequently worth being further optimized. Herein, we present the one-pot two-step procedure for the synthesis of a set of pyrazolo[3,4-d]pyrimidine prodrugs (1a−8a and 9a−e) with higher aqueous solubility and enhanced pharmacokinetic and therapeutic properties. ADME

  吡唑并[3,4- d ]嘧啶是有效的蛋白激酶抑制剂，具有有希望的抗肿瘤活性，但水溶性较差，因此值得进一步优化。在这里，我们提出了一锅两步程序，用于合成一组具有较高水溶性和增强的药代动力学和治疗特性的吡唑并[3,4- d ]嘧啶前药（1a - 8a和9a - e）。ADME研究表明，最有前途的前药具有更好的水溶性，在人和鼠血清中具有良好的水解作用，并且相对于母体药物而言，其跨细胞膜的能力增强，这说明了它们在体外24小时的性能更好对人胶质母细胞瘤U87细胞系的细胞毒性。最后，还对体内的4–4a药物/前药进行了评估，揭示了前药具有良好疗效的有利的药代动力学特征。事实证明，前药方法的应用是提高母体药物水溶性的成功策略，对它们的生物学功效也产生了积极影响。
• [EN] SUBSTITUTED PYRAZOLO[1,5-a]PYRAZINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRAZOLO[1,5-A]PYRAZINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE RET
  申请人：ANDREWS STEVEN W

  公开号：WO2018136661A1

  公开（公告）日：2018-07-26

  Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供了Formula I的化合物及其立体异构体和药学上可接受的盐或溶剂，其中A、B、D、E、X1、X2、X3和X4在规范中给出的含义，这些化合物是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括由RET激酶介导的疾病或紊乱。
• Lokalanästhetisch wirksame Carbaminsäure-und Alkylkohlensäure-Ester heterocyclischer Aminoalkohole
  作者：Marc Häring

  DOI：10.1002/hlca.19590420619

  日期：——

  Es wurde eine Reihe von Alkylkohlensäure- und Carbaminsäure-Estern hetero-cyclischer Aminoalkohole der allgemeinen Formel

  制备了许多具有通式的杂环氨基醇的烷基碳酸酯和氨基甲酸酯
• Serotonin Reuptake Inhibitors
  申请人：Pinney Kevin G.

  公开号：US20080132514A1

  公开（公告）日：2008-06-05

  A serotonin reuptake inhibitor which can be used in the treatment of depression and which has a decreased occurrence of unwanted side effects. The serotonin reuptake inhibitors are bi-functional organic molecules which combine serotonin transporter reuptake inhibition with serotonin (5-HT, such as 5-HT2A) receptor antagonism in one molecular entity. The serotonin-selective reuptake inhibitor (SSRI) homologue portion of the molecule shows an affinity to the serotonin reuptake transporter (SERT) and has antidepressant properties. The piperazine or piperidine portion of the molecule demonstrates an affinity to 5-HT receptors and restores the undesired side effects of SSRIs.

  一种能够用于治疗抑郁症且不良副作用发生率降低的5-羟色胺再摄取抑制剂。 5-羟色胺再摄取抑制剂是一种双功能的有机分子，它将5-羟色胺转运体再摄取抑制与5-羟色胺（如5-HT2A）受体拮抗结合在一个分子实体中。分子中的5-羟色胺选择性再摄取抑制剂（SSRI）同源物部分显示出对5-羟色胺再摄取转运体（SERT）的亲和力，并具有抗抑郁作用。分子中的哌嗪或哌啶部分显示出对5-HT受体的亲和力，并恢复了SSRI的不良副作用。