3-(4-methylpiperazin-1-yl)phenol | 177489-10-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(4-methylpiperazin-1-yl)phenol
• 英文别名: 1-methyl-4-m-hydroxyphenylpiperazine
• CAS: 177489-10-0
• 化学式: C₁₁H₁₆N₂O
• 分子量: 192.261
• InChiKey: AISHPJPGKBKMGV-UHFFFAOYSA-N

物化性质

• 沸点：
  345.4±37.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 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：

  3-(4-methylpiperazin-1-yl)phenol 以 乙醚 、 氯仿 为溶剂， 反应 4.0h， 生成 4-(3-Acetoxy-phenyl)-1,1-dimethyl-piperazin-1-ium; iodide
  参考文献：
  名称：

  Structure−Affinity Relationships of a Unique Nicotinic Ligand:  N-Dimethyl-N⁴-phenylpiperazinium Iodide (DMPP)

  摘要：

  DMPP is a well-known nicotinic agonist that does not fit any proposed pharmacophore for nicotinic binding and represents a unique ligand among the hundreds of nicotinic agonists studied in the past decades. A systematic modulation of the chemical structure of DMPP, aimed to establish its structure-affinity relationships, is reported. The research has allowed to identify molecules such as I Ic, 13c, 14c, and 28c, with affinities for alpha (4)beta (2) receptors in the low nanomolar range, some 2 orders of magnitude lower than the lead compound. The agonistic properties of the most interesting compounds have been assessed by measuring their analgesic activity on mice (hot-plate test). Another result of the research was the identification of DMPP analogues, such as 3a (K-i = 90 nM) and 14b (K-i = 180 nM), that maintain affinity for the central nicotinic receptor when the ammonium function is changed into an aminic one and are therefore possible leads for drug development in neurodegenerative diseases.

  DOI：

  10.1021/jm010901y
• 作为产物：
  描述：

  间羟基苯基哌嗪 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 反应 18.0h， 生成 3-(4-methylpiperazin-1-yl)phenol
  参考文献：
  名称：

  Identification of 2-arylbenzimidazoles as potent human histamine H4 receptor ligands

  摘要：

  A series of 2-arylbenzimidazoles was synthesized and found to bind with high affinity to the human histamine H(4) receptor. Structure-activity relationships were investigated through library preparation and evaluation as well as traditional medicinal chemistry approaches, leading to the discovery of compounds with single-digit nanomolar affinity for the H(4) receptor.

  DOI：

  10.1016/j.bmcl.2006.08.117

文献信息

• A Highly Versatile Catalyst System for the Cross-Coupling of Aryl Chlorides and Amines
  作者：Rylan J. Lundgren、Antonia Sappong-Kumankumah、Mark Stradiotto

  DOI：10.1002/chem.200902316

  日期：2010.2.8

  air‐stable P,N ligands enable the cross‐coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcohols, olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl‐ and arylamines, cyclic and acyclic secondary amines, NH imines, hydrazones, lithium amide, and ammonia

  2-（二-的合成叔- -butylphosphino）ñ，Ñ二甲基苯胺（L1，71％）和2-（二-1- adamantylphosphino） - ñ，Ñ二甲基苯胺（L2，74％），和它们的应用据报道在布赫瓦尔德-哈特维格胺的胺化反应。与[Pd（烯丙基）Cl] 2或[Pd（肉桂基）Cl] 2组合，这些结构简单且稳定的P，N配体可实现芳基和杂芳基氯化物的交叉偶联，包括带有可取代的酮，醚，酯，羧酸，酚，醇，烯烃，酰胺和卤素的取代基。胺和相关的基板的一个不同的范围，其包括初级烷基-和芳基胺，环状和非环状仲胺，N  ħ亚胺，腙，氨基锂，和氨。在许多情况下，反应可以在低催化剂负载量（0.5–0.02 mol％Pd）下进行，且具有出色的官能团耐受性和化学选择性。还报道了涉及1,4-溴氯苯和碘苯的交叉偶联反应的例子。在相似的条件下，使用Pd（OAc）2可获得较差的催化性能，PdCl 2，[PdCl 2（cod）]（cod
• [EN] SUBSTITUTED PYRAZOLO-QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLO-QUINAZOLINE SUBSTITUÉS À TITRE D'INHIBITEURS DE KINASES
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2012080990A1

  公开（公告）日：2012-06-21

  The present invention relates to substituted pyrazolo[4,3-/h]quinazoline compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular PIM kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

  本发明涉及替代吡唑并[4,3-/h]喹唑啉化合物，其调节蛋白激酶的活性，因此在治疗由失调的蛋白激酶活性引起的疾病方面具有用处，特别是PIM激酶。本发明还提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用这些化合物或含有它们的药物组合物治疗疾病的方法。
• Synthesis and anticancer activity of novel water soluble benzimidazole carbamates
  作者：Jae Eun Cheong、Michela Zaffagni、Ivy Chung、Yingjie Xu、Yiqiang Wang、Finith E. Jernigan、Bruce R. Zetter、Lijun Sun

  DOI：10.1016/j.ejmech.2017.11.037

  日期：2018.1

  of advanced metastatic cancers. The benzimidazole methylcarbamate drugs, commonly used as anti-helmitics, have been suggested to have anticancer activity, but progress has been stalled by their poor water solubility and poor suitability for systemic delivery to disseminated cancers. We synthesized and characterized the anticancer activity of novel benzimidazoles containing an oxetane or an amine group

  转移占所有癌症死亡的90％以上，并且对大多数疗法的反应较差。迫切需要用于治疗晚期转移性癌症的新治疗方式。苯并咪唑甲基氨基甲酸酯药物，通常用作抗蠕虫药，已被证明具有抗癌活性，但由于其水溶性差和对全身性扩散性癌症的适应性差，进展一直受阻。我们合成并表征了新的含氧杂环丁烷或胺基的苯并咪唑类化合物的抗癌活性，以提高其溶解度。其中，新型氧杂环丁烷基取代的化合物18对多种类型的癌细胞（包括前列腺癌，肺癌和卵巢癌）表现出显着的细胞毒性，对高度侵袭性的癌细胞系具有很强的活性（IC 50：0.9-3.8μM）。化合物18的水溶解度为361μM。在高度转移性人类前列腺癌的小鼠异种移植模型中，化合物18（30 mg / kg）显着抑制已建立肿瘤的生长（T / C：0.36），而没有明显的毒性。
• SUBSTITUTED PYRAZOLO-QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS
  申请人：Casuscelli Francesco

  公开号：US20120190678A1

  公开（公告）日：2012-07-26

  The present invention relates to substituted pyrazolo[4,3-h]quinazoline compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular PIM kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

  本发明涉及替代吡唑并[4,3-h]喹唑啉化合物，其调节蛋白激酶的活性，因此在治疗由失调的蛋白激酶活性引起的疾病方面具有用处，特别是PIM激酶。本发明还提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用这些化合物或含有它们的药物组合物治疗疾病的方法。
• Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology
  作者：Manjunath Lamani、Michael S. Malamas、Shrouq I. Farah、Vidyanand G. Shukla、Michael F. Almeida、Catherine M. Weerts、Joseph Anderson、JodiAnne T. Wood、Karen L.G. Farizatto、Ben A. Bahr、Alexandros Makriyannis

  DOI：10.1016/j.bmc.2019.115096

  日期：2019.12

  and selective carbamate FAAH inhibitors and the evaluation for neuroprotection. The new inhibitors showed potent nanomolar inhibitory activity against human recombinant and purified rat FAAH, were selective (>1000-fold) against serine hydrolases MGL and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Evaluation of FAAH inhibitors 9 and 31 using the in vitro competitive activity-based

  FAAH抑制剂可通过“按需”增加anandamide含量来增强神经保护机制，从而提供安全优势，而不会产生通常直接或长期激活CB1受体会产生的不良精神影响。FAAH是与内源性大麻素N-花生四烯酰乙醇胺（AEA）水解有关的酶，AEA是CB1受体的部分激动剂。在这里，我们报告发现了一系列新的高效和选择性氨基甲酸酯FAAH抑制剂的发现以及对神经保护作用的评估。新抑制剂显示出对人重组和纯化大鼠FAAH的有效纳摩尔抑制活性，对丝氨酸水解酶MGL和ABHD6具有选择性（> 1000倍），并且对大麻素受体CB1和CB2没有亲和力。FAAH抑制剂的评估使用基于体外竞争活性的蛋白质谱（ABPP）分析的图9和31证实这两种抑制剂对大脑中的FAAH具有高度选择性，因为该组织中的其他FP反应性丝氨酸水解酶均不受这些试剂的抑制。我们的设计策略遵循传统的SAR方法，并得到了基于已知FAAH共晶体结构的分子建模研究的支持