4-(N-piperidinyl)methyl benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(N-piperidinyl)methyl benzoic acid
• 英文别名: 4-(piperidin-1-yl)methylbenzoic acid；4-(piperidin-1-ium-1-ylmethyl)benzoate
• 化学式: C₁₃H₁₇NO₂
• mdl: MFCD05240080
• 分子量: 219.283
• InChiKey: RNCCMTVMMFUIKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(N-piperidinyl)methyl benzoic acid 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(piperidin-1-ylmethyl)benzoyl chloride
  参考文献：
  名称：

  Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents

  摘要：

  In present study, 4-anilinoquinazolines scaffold, arylurea and tertiary amine moiety were combined to design, synthesize gefitinib analogs and discover novel anticancer agents. A series of 4-anilinoquinazoline derivatives (1, 2, 3 and 4) bearing arylurea and tertiary amine moiety at its 6-position were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against A431 cell and A549 cell. The SAR of the title compounds was discussed. The compounds 2d, 2i and 2j with potent antiproliferative activities were evaluated their inhibitory activity against EGFR-TK. Compound 2j displayed potent inhibitory activity against EGFR-TK. In addition, compound 2j, at 50 mg/kg, can completely inhibit cancer growth in established nude mouse A549 xenograft model in vivo. These results suggest that the 4-anilinoquinazoline derivatives bearing diarylurea and tertiary amino moiety at its 6-position can serve as anticancer agents and EGFR inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.001
• 作为产物：
  描述：

  4-(1-哌啶基甲基)苯甲酸甲酯 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 4-(N-piperidinyl)methyl benzoic acid
  参考文献：
  名称：

  [EN] BENZAMIDE DERIVATIVES FOR INHIBITING ENDOPLASMIC RETICULUM (ER) STRESS
  [FR] DÉRIVÉS DE BENZAMIDE PERMETTANT D'INHIBER LE STRESS DU RÉTICULUM ENDOPLASMIQUE (ER)

  摘要：

  披露了新型3-(N-哌啶基)甲基苯甲酰胺衍生物。这些化合物可用于治疗与内质网（ER）应激相关的异常细胞功能引起的疾病和症状。例如，这些化合物可用作抑制ER应激诱导的胰岛素β细胞功能障碍和死亡的药物，例如用于治疗糖尿病。

  公开号：

  WO2018232264A1

文献信息

• Novel Benzohydroxamate-Based Potent and Selective Histone Deacetylase 6 (HDAC6) Inhibitors Bearing a Pentaheterocyclic Scaffold: Design, Synthesis, and Biological Evaluation
  作者：Barbara Vergani、Giovanni Sandrone、Mattia Marchini、Chiara Ripamonti、Edoardo Cellupica、Elisabetta Galbiati、Gianluca Caprini、Gianfranco Pavich、Giulia Porro、Ilaria Rocchio、Maria Lattanzio、Marcello Pezzuto、Malgorzata Skorupska、Paola Cordella、Paolo Pagani、Pietro Pozzi、Roberta Pomarico、Daniela Modena、Flavio Leoni、Raffaella Perego、Gianluca Fossati、Christian Steinkühler、Andrea Stevenazzi

  DOI：10.1021/acs.jmedchem.9b01194

  日期：2019.12.12

  Histone deacetylase 6 (HDAC6) is a peculiar HDAC isoform whose expression and functional alterations have been correlated with a variety of pathologies such as autoimmune disorders, neurodegenerative diseases, and cancer. It is primarily a cytoplasmic protein, and its deacetylase activity is focused mainly on nonhistone substrates such as tubulin, heat shock protein (HSP)90, Foxp3, and cortactin, to

  组蛋白脱乙酰基酶6（HDAC6）是一种特殊的HDAC亚型，其表达和功能改变已与多种病理学相关，例如自身免疫性疾病，神经退行性疾病和癌症。它主要是一种细胞质蛋白，其脱乙酰酶活性主要集中在非组蛋白底物上，例如微管蛋白，热休克蛋白（HSP）90，Foxp3和cortactin等。HDAC6的选择性抑制在健康细胞中不显示细胞毒性作用，通常与I类HDAC同工型的抑制有关。在这里，我们描述了带有五杂环中央核心的新型有效和选择性HDAC6抑制剂的设计和合成。
• Application of<i>N</i>-substituted (aminomethyl)benzoate Strategy in Design of Scutellarein Derivatives with Improved Caco-2 Cell Permeability and<i>In Vitro</i>Antioxidative Activity
  作者：Ze-Qin Dai、Hang Su、Min Luo、Yu Ou、Xiao-Zhong Fu、Yong-Xi Dong、Yu-Feng Cha、Shun Zhang、Yong Huang、Yong-Lin Wang

  DOI：10.1002/bkcs.10377

  日期：2015.8

  A series of 4′‐N‐substituted (aminomethyl)benzoate derivatives of scutellarein were designed and synthesized. Evaluation of their physiochemical properties showed that the designed target compounds 5a–e exhibit higher chemical stability and aqueous solubility than scutellarin and scutellarein. The permeability (P app AP to BL ) of 5c–e in Caco‐2 cells were 2.8, 8.1, and 12.6 times higher than that

  设计并合成了一系列黄cut素的4'- N-取代（氨基甲基）苯甲酸酯衍生物。对它们的理化性质的评估表明，所设计的目标化合物5a–e与黄cut苷和黄cut苷相比，具有更高的化学稳定性和水溶性。Caco-2细胞中5c–e的渗透率（P app AP 对 BL）分别比黄素高2.8、8.1和12.6倍，比黄re素高1.3、4.1和6.0倍。特别是5e具有最高的P app AP到BL值（7.19±0.31×10 -6  cm / s）和最低的ER（P app BL to AP / P app AP to BL）值0.17。体外抗氧化评估结果表明5e可以通过减轻线粒体膜电位损失并减少H 2 O 2诱导的活性氧（ROS）的产生来防御H 2 O 2诱导的PC12细胞的氧化损伤。
• Permeability of novel 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein in Caco-2 cells and in an in vitro model of the blood-brain barrier
  作者：Yu Ou、Min Luo、Yong-Xi Dong、Hang Su、Xiao-Zhong Fu、Yu-Feng Cha、Shun Zhang、Yong-Long Zhao、Yong-Jun Li、Yong-Lin Wang

  DOI：10.1007/s00044-016-1659-y

  日期：2016.10

  A series of 4′-N-substituted (aminomethyl) benzoate-7-substituted nicotinic acid ester derivatives of scutellarein was designed and synthesized. Evaluation of physiochemical properties showed that the newly designed compounds had greater chemical stability and aqueous solubility than scutellarin or scutellarein. The permeabilities (P app AP to BL) of compounds 7b and 7e in Caco-2 cells were 5.9-fold

  一系列的4' - ñ -取代的（氨基甲基）野黄芩素的苯甲酸-7-取代烟酸酯衍生物设计并合成。理化性质的评估表明，新设计的化合物比黄苷或黄cut苷具有更高的化学稳定性和水溶性。化合物7b和7e在Caco-2细胞中的渗透率（P app AP对BL）比黄素高5.9倍和3.7倍，比黄cut素高3.7倍和2.4倍。化合物7b和7e的磁导率（P app AP到BL） 在体外模型中，血脑屏障比黄cut素高9.7倍和5.9倍，比黄cut素高9.2倍和5.6倍。
• [EN] BENZAMIDE DERIVATIVES FOR INHIBITING ENDOPLASMIC RETICULUM (ER) STRESS<br/>[FR] DÉRIVÉS DE BENZAMIDE PERMETTANT D'INHIBER LE STRESS DU RÉTICULUM ENDOPLASMIQUE (ER)
  申请人：UNIV OKLAHOMA

  公开号：WO2018232264A1

  公开（公告）日：2018-12-20

  Novel 3-(N-piperidinyl)methyl benzamide derivatives are disclosed. The compounds can be used in treating diseases and conditions which are associated with abnormal cell function related to endoplasmic reticulum (ER) stress. For example, the compounds can be used as suppressors of ER stress-induced pancreatic β-cell dysfunction and death, for example in the treatment of diabetes.

  披露了新型3-(N-哌啶基)甲基苯甲酰胺衍生物。这些化合物可用于治疗与内质网（ER）应激相关的异常细胞功能引起的疾病和症状。例如，这些化合物可用作抑制ER应激诱导的胰岛素β细胞功能障碍和死亡的药物，例如用于治疗糖尿病。
• Imatinib base, and imatinib mesylate and processes for preparation thereof
  申请人：MacDonald Peter

  公开号：US20080207904A1

  公开（公告）日：2008-08-28

  The present invention provides crystalline forms of imatinib base, imatinib base free of desmethyl imatinib, and imatinib mesylate free of desmethyl imatinib mesylate, processes of their preparation and pharmaceutical compositions of imatinib mesylate.

  本发明提供了伊马替尼基质的晶体形式，不含去甲基伊马替尼的伊马替尼基质，以及不含去甲基伊马替尼甲磺酸盐的伊马替尼甲磺酸盐，它们的制备过程和伊马替尼甲磺酸盐的药物组成物。