4-(4-methylpiperazine-1-carbonyl)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(4-methylpiperazine-1-carbonyl)benzoic acid
• 化学式: C₁₃H₁₆N₂O₃
• mdl: MFCD05862600
• 分子量: 248.282
• InChiKey: AXLBYXDLGXVEHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-methylpiperazine-1-carbonyl)benzoic acid 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 1-(3,5-dimethoxyphenyl)-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)urea
  参考文献：
  名称：

  具有4-甲基哌嗪基羰基部分的二芳基脲衍生物的合成和细胞毒活性

  摘要：

  通过异氰酸酯与芳基胺的反应合成了11个带有N-甲基哌嗪基部分的二芳基脲衍生物（1a-1k）。1a–1k的结构通过1 H-NMR和MS表征。通过MTT方法评估了1a-1k的细胞毒性活性对人肺腺癌上皮细胞系A549和人前列腺癌细胞系PC3的影响。化合物1d和1k显示出强大的细胞毒活性。结果表明，活性与另一个苯环上的取代基有很大关系。

  DOI：

  10.1007/s00044-012-0398-y
• 作为产物：
  描述：

  4-氯甲酰基苯甲酸甲酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 4-(4-methylpiperazine-1-carbonyl)benzoic acid
  参考文献：
  名称：

  具有4-甲基哌嗪基羰基部分的二芳基脲衍生物的合成和细胞毒活性

  摘要：

  通过异氰酸酯与芳基胺的反应合成了11个带有N-甲基哌嗪基部分的二芳基脲衍生物（1a-1k）。1a–1k的结构通过1 H-NMR和MS表征。通过MTT方法评估了1a-1k的细胞毒性活性对人肺腺癌上皮细胞系A549和人前列腺癌细胞系PC3的影响。化合物1d和1k显示出强大的细胞毒活性。结果表明，活性与另一个苯环上的取代基有很大关系。

  DOI：

  10.1007/s00044-012-0398-y

文献信息

• FUNCTIONALLY-MODIFIED OLIGONUCLEOTIDES AND SUBUNITS THEREOF
  申请人：Sarepta Therapeutics, Inc.

  公开号：US20140330006A1

  公开（公告）日：2014-11-06

  Functionally-modified oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3′ and/or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

  提供了包含修改的亚单位间连接和/或修改的3'和/或5'-末端基团的功能修饰寡核苷酸类似物。所公开的化合物对于治疗需要抑制蛋白质表达或纠正异常mRNA剪接产物以产生有益治疗效果的疾病是有用的。
• PYRROLO[2,1-F][1,2,4]TRIAZINE COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：US20150141644A1

  公开（公告）日：2015-05-21

  The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

  本发明涉及一种吡咯并[2,1-f][1,2,4]三嗪化合物，其异构体或药学上可接受的盐、酯或水合物，以及其制备方法和应用。吡咯并[2,1-f][1,2,4]三嗪化合物具有一般式(I)表示的结构。一般式(I)表示的吡咯并[2,1-f][1,2,4]三嗪化合物可以抑制磷脂酰肌醇-3激酶（PI3K）信号通路，因此可用于制备用于治疗磷脂酰肌醇-3激酶相关疾病如癌症的药物。
• Pyrrolo[2,1-f][1,2,4]triazine compound, and preparation method and application thereof
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：US09447101B2

  公开（公告）日：2016-09-20

  The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

  本发明涉及一种吡咯并[2,1-f][1,2,4]三嗪化合物、其异构体或其药学上可接受的盐、酯或水合物，以及其制备方法和应用。该吡咯并[2,1-f][1,2,4]三嗪化合物具有通式(I)所表示的结构。通式(I)所表示的吡咯并[2,1-f][1,2,4]三嗪化合物能够抑制磷脂酰肌醇-3激酶（PI3K）信号通路，因此可用于制备治疗磷脂酰肌醇-3激酶相关疾病如癌症的药物。
• Design and Synthesis of Tri-Ring P₃ Benzamide-Containing Aminonitriles as Potent, Selective, Orally Effective Inhibitors of Cathepsin K
  作者：James T. Palmer、Clifford Bryant、Dan-Xiong Wang、Dana E. Davis、Eduardo L. Setti、Robert M. Rydzewski、Shankar Venkatraman、Zong-Qiang Tian、Leland C. Burrill、Rohan V. Mendonca、Eric Springman、John McCarter、Tobee Chung、Harry Cheung、James W. Janc、Mary McGrath、John R. Somoza、Philip Enriquez、Z. Walter Yu、Robert M. Strickley、Liang Liu、Michael C. Venuti、M. David Percival、Jean-Pierre Falgueyret、Peppi Prasit、Renata Oballa、Denis Riendeau、Robert N. Young、Gregg Wesolowski、Sevgi B. Rodan、Colena Johnson、Donald B. Kimmel、Gideon Rodan

  DOI：10.1021/jm058198r

  日期：2005.12.1

  We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P-2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/ L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.
• Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold
  作者：Claire-Lise Ciana、Romain Siegrist、Hamed Aissaoui、Léo Marx、Sophie Racine、Solange Meyer、Christoph Binkert、Ruben de Kanter、Christoph Fischli、Sergio Wittlin、Christoph Boss

  DOI：10.1016/j.bmcl.2012.11.118

  日期：2013.2

  A novel series of anti-malarials, based on a hydroxy-ethyl-amine scaffold, initially identified as peptidomimetic protease inhibitors is described. Combination of the hydroxy-ethyl-amine anti-malarial phramacophore with the known Mannich base pharmacophore of amodiaquine (57) resulted in promising in vivo active novel derivatives. (c) 2012 Elsevier Ltd. All rights reserved.