3-(4-甲基哌嗪基)苯甲醛 | 628325-62-2

• 物质功能分类: 医药中间体 - 哌嗪类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 3-(4-甲基哌嗪基)苯甲醛
• 中文别名: 3-(4-甲基哌嗪-1-基)苯甲醛
• 英文名称: 3-(4-methyl-1-piperazinyl)benzaldehyde
• 英文别名: 3-(4-methylpiperazin-1-yl)benzaldehyde
• CAS: 628325-62-2
• 化学式: C₁₂H₁₆N₂O
• mdl: MFCD09030500
• 分子量: 204.272
• InChiKey: LQDFMHOZQXAHNJ-UHFFFAOYSA-N

物化性质

• 沸点：
  344.8±37.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  3-(4-甲基哌嗪基)苯甲醛 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以95%的产率得到2-溴-5-(4-甲基哌嗪-1-基)苯甲醛
  参考文献：
  名称：

  Cationic Chalcone Antibiotics. Design, Synthesis, and Mechanism of Action

  摘要：

  This paper describes how the introduction of "cationic" aliphatic amino groups in the chalcone scaffold results in potent antibacterial compounds. It is shown that the most favorable position for the aliphatic amino group is the 2-position of the B-ring, in particular in combination with a lipophilic substituent in the 5-position of the beta-ring. We demonstrate that the compounds act by unselective disruption of cell membranes. Introduction of an additional aliphatic amino group in the A-ring results in compounds that are selective for bacterial membranes combined with a high antibacterial activity against both Gram-positive and -negative pathogens. The most potent compound in this study (78) has an MIC value of 2 mu M against methicillin resistant Staphylococus aureus.

  DOI：

  10.1021/jm049424k
• 作为产物：
  描述：

  2-(3-溴苯基)-1,3-二恶烷 在 盐酸 、 tris(dibenzylideneacetone)dipalladium (0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 20.0h， 生成 3-(4-甲基哌嗪基)苯甲醛
  参考文献：
  名称：

  Cationic Chalcone Antibiotics. Design, Synthesis, and Mechanism of Action

  摘要：

  This paper describes how the introduction of "cationic" aliphatic amino groups in the chalcone scaffold results in potent antibacterial compounds. It is shown that the most favorable position for the aliphatic amino group is the 2-position of the B-ring, in particular in combination with a lipophilic substituent in the 5-position of the beta-ring. We demonstrate that the compounds act by unselective disruption of cell membranes. Introduction of an additional aliphatic amino group in the A-ring results in compounds that are selective for bacterial membranes combined with a high antibacterial activity against both Gram-positive and -negative pathogens. The most potent compound in this study (78) has an MIC value of 2 mu M against methicillin resistant Staphylococus aureus.

  DOI：

  10.1021/jm049424k

文献信息

• NOVEL INHIBITORS
  申请人：Heiser Ulrich

  公开号：US20110092501A1

  公开（公告）日：2011-04-21

  The invention relates to novel pyrrolidine derivatives of formula (I): wherein R 1 , R 2 and R 3 are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

  本发明涉及新颖的吡咯烷衍生物，其具有如下公式(I)：其中R1、R2和R3如本文所述定义，作为谷氨酰胺环化酶（QC，EC 2.3.2.5）的抑制剂。谷氨酰胺环化酶催化N末端谷氨酰胺残基形成焦谷氨酸（5-氧代脯氨酸，pGlu*）的分子内环化，并释放氨，以及催化N末端谷氨酸残基形成焦谷氨酸的分子内环化，并释放水。
• Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors
  作者：Chao Che、Song Li、Bo Yang、Shengchang Xin、Zhixiong Yu、Taofeng Shao、Chuanye Tao、Shuo Lin、Zhen Yang

  DOI：10.3762/bjoc.8.94

  日期：——

  Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure–activity relationship of this important class of hedgehog-pathway inhibitors.

  Sant-75是一种新发现的对刺猬途径具有强大抑制作用的抑制剂。我们设计了一个多样性定向合成计划，并合成了一系列Sant-75类似物，为进一步研究这一重要类别的刺猬途径抑制剂的结构-活性关系奠定了基础。
• Optimization of Imidazo[4,5-<i>b</i>]pyridine-Based Kinase Inhibitors: Identification of a Dual FLT3/Aurora Kinase Inhibitor as an Orally Bioavailable Preclinical Development Candidate for the Treatment of Acute Myeloid Leukemia
  作者：Vassilios Bavetsias、Simon Crumpler、Chongbo Sun、Sian Avery、Butrus Atrash、Amir Faisal、Andrew S. Moore、Magda Kosmopoulou、Nathan Brown、Peter W. Sheldrake、Katherine Bush、Alan Henley、Gary Box、Melanie Valenti、Alexis de Haven Brandon、Florence I. Raynaud、Paul Workman、Suzanne A. Eccles、Richard Bayliss、Spiros Linardopoulos、Julian Blagg

  DOI：10.1021/jm300952s

  日期：2012.10.25

  children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, 27e strongly inhibited the growth of a FLT3-ITD-positive AML human tumor xenograft (MV4–11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound 27e, an orally bioavailable dual FLT3 and

  对基于咪唑并[4,5 - b ]吡啶的系列极光激酶抑制剂进行优化，鉴定出 6-chloro-7-(4-(4-chlorobenzyl)pirazin-1-yl)-2-(1, 3-dimethyl-1 H -pyrazol-4-yl)-3 H -imidazo[4,5- b ]pyridine ( 27e )，一种强效的 Aurora 激酶抑制剂 (Aurora-A K d = 7.5 nM, Aurora-B K d = 48 nM)、FLT3 激酶 ( K d = 6.2 nM) 和 FLT3 突变体，包括 FLT3-ITD ( K d = 38 nM) 和 FLT3(D835Y) ( K d = 14 nM)。FLT3-ITD 引起组成型 FLT3 激酶激活，在 20-35% 的成人和 15% 的急性髓性白血病 (AML) 患儿中检测到，这两个年龄组的预后都很差。在体内环境中，27e在口服给药后强烈抑制FLT3
• Design, synthesis and biological evaluation of chalcones as reversers of P-glycoprotein-mediated multidrug resistance
  作者：Huanhuan Yin、Jingjing Dong、Yingchun Cai、Ximeng Shi、Hao Wang、Guixia Liu、Yun Tang、Jianwen Liu、Lei Ma

  DOI：10.1016/j.ejmech.2019.05.053

  日期：2019.10

  become a major obstacle in cancer therapy. One hopeful approach to reverse the MDR is to develop inhibitors of P-gp in expression and/or function. Here, we designed and synthesized a series of chalcone derivatives as P-gp inhibitors and evaluated their potential reversal activities against MDR. Among them, the most active compound MY3 had little intrinsic cytotoxicity and showed the highest activity

  P-糖蛋白（P-gp）的过表达是多药耐药性（MDR）的主要原因之一，它已成为癌症治疗的主要障碍。逆转MDR的一种有希望的方法是开发在表达和/或功能上的P-gp抑制剂。在这里，我们设计和合成了一系列查尔酮衍生物作为P-gp抑制剂，并评估了它们对MDR的潜在逆转活性。其中，活性最高的化合物MY3几乎没有内在的细胞毒性，并且在逆转MCF-7 / DOX细胞中的DOX耐药性方面显示出最高的活性（RF = 50.19）。进一步的研究表明，MY3可以增加DOX在细胞内的积累，并在mRNA和蛋白质水平上抑制P-gp的表达。更重要的是，MY3在不改变体重的前提下，显着增强了DOX对抗带有MCF-7 / DOX细胞的肿瘤异种移植物的功效。因此，MY3可能代表开发用于癌症化疗的MDR逆转剂的有希望的领先者。
• [EN] PIPERIDINYL AMINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE<br/>[FR] COMPOSÉS DE PIPÉRIDINYL AMINE POUR LE TRAITEMENT D'UNE MALADIE AUTO-IMMUNE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021052892A1

  公开（公告）日：2021-03-25

  The present invention relates to compounds of formula (I), wherein R1, R2, R3, R4 and R5 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

  本发明涉及公式（I）的化合物，其中R1、R2、R3、R4和R5如本文所述，并且它们的药用盐、对映体或二对映体，以及包括该化合物的组合物和使用该化合物的方法。