2-甲基-5-((3-(三氟甲基)苯基)氨基甲酰基)苯甲酸 | 1018069-85-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-甲基-5-((3-(三氟甲基)苯基)氨基甲酰基)苯甲酸
• 英文名称: 2-methyl-5-((3-(trifluoromethyl)phenyl)carbamoyl)benzoic acid
• 英文别名: 2-Methyl-5-(3-(trifluoromethyl)phenylcarbamoyl)benzoic acid；2-methyl-5-[[3-(trifluoromethyl)phenyl]carbamoyl]benzoic acid
• CAS: 1018069-85-6
• 化学式: C₁₆H₁₂F₃NO₃
• 分子量: 323.271
• InChiKey: FDQNGMZKIUOERJ-UHFFFAOYSA-N

物化性质

• 沸点：
  389.8±42.0 °C(Predicted)
• 密度：
  1.401±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,5-二氨基嘧啶 、 2-甲基-5-((3-(三氟甲基)苯基)氨基甲酰基)苯甲酸 在 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N3-(2-amino-5-pyrimidinyl)-4-methyl-N1-(3-(trifluoromethyl)phenyl)-1,3-benzenedicarboxamide
  参考文献：
  名称：

  Discovery of a potent and selective c-Kit inhibitor for the treatment of inflammatory diseases

  摘要：

  A potent and selective c-Kit inhibitor 20 was identified through a structure-activity relationship study. In an in vivo mouse model of mast cell activation, 20 blocked the SCF-induced histamine release with an EC(50) of 26 nM. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.089
• 作为产物：
  描述：

  2-甲基-5-((3-(三氟甲基)苯基)氨基甲酰基)苯甲酸甲酯 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 20.0h， 以92%的产率得到2-甲基-5-((3-(三氟甲基)苯基)氨基甲酰基)苯甲酸
  参考文献：
  名称：

  Structure-Guided Design of Aminopyrimidine Amides as Potent, Selective Inhibitors of Lymphocyte Specific Kinase: Synthesis, Structure–Activity Relationships, and Inhibition of in Vivo T Cell Activation

  摘要：

  The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic evidence, including knockout mice and human mutations, demonstrates that Lck kinase activity is critical for normal T cell development, activation, and signaling. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. With the aid of X-ray structure-based analysis, aminopyrimidine amides 2 and 3 were designed from aminoquinazolines 1, which had previously been demonstrated to exhibit potent inhibition of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminopyrimidine amides 3 possessing improved cellular potency and selectivity profiles relative to their aminoquinazoline predecessors 1. Orally bioavailable compound 13b inhibited the anti-CD3-induced production of interleukin-2 (IL-2) in mice in a dose-dependent manner (ED50 = 9.4 mg/kg).

  DOI：

  10.1021/jm7010996

文献信息

• Discovery of a Series of 2,5-Diaminopyrimidine Covalent Irreversible Inhibitors of Bruton’s Tyrosine Kinase with in Vivo Antitumor Activity
  作者：Xitao Li、Yingying Zuo、Guanghui Tang、Yan Wang、Yiqing Zhou、Xueying Wang、Tianlin Guo、Mengying Xia、Ning Ding、Zhengying Pan

  DOI：10.1021/jm4017762

  日期：2014.6.26

  Bruton’s tyrosine kinase (Btk) is an attractive drug target for treating several B-cell lineage cancers. Ibrutinib is a first-in-class covalent irreversible Btk inhibitor and has demonstrated impressive effects in multiple clinical trials. Herein, we present a series of novel 2,5-diaminopyrimidine covalent irreversible inhibitors of Btk. Compared with ibrutinib, these inhibitors exhibited a different

  Bruton的酪氨酸激酶（Btk）是治疗几种B细胞谱系癌症的引人注目的药物靶标。依鲁替尼是一流的共价不可逆Btk抑制剂，在多项临床试验中已显示出令人印象深刻的效果。在本文中，我们介绍了一系列新型的Btk 2，5-二氨基嘧啶共价不可逆抑制剂。与依鲁替尼相比，这些抑制剂对所分析的激酶表现出不同的选择性，并具有抑制Btk活化和催化活性的双重作用模式，从而抵消了Btk的负调节回路。该系列中的两种化合物31和38，显示出对多种B细胞淋巴瘤细胞系的有效抗增殖活性，包括生发中心B细胞样弥散性大B细胞淋巴瘤（GCB-DLBCL）细胞。另外，化合物31在小鼠异种移植模型中显着阻止了肿瘤的生长。
• KINASE INHIBITOR AND METHOD FOR TREATMENT OF RELATED DISEASES
  申请人：Peking University Shenzhen Graduate School

  公开号：EP2772486A1

  公开（公告）日：2014-09-03

  Disclosed is a compound of (aminophenylamino) pyrimidyl benzamides and a synthesis method thereof. The compound has Btk-inhibition activity and can be used to treat autoimmune diseases, heteroimmune diseases, cancers or thromboembolic diseases.

  本发明公开了一种（氨基苯氨基）嘧啶基苯甲酰胺化合物及其合成方法。该化合物具有 Btk 抑制活性，可用于治疗自身免疫性疾病、异种免疫性疾病、癌症或血栓栓塞性疾病。
• EP2772486B1
  申请人：——

  公开号：EP2772486B1

  公开（公告）日：2016-03-16
• US20140256759A1
  申请人：——

  公开号：US20140256759A1

  公开（公告）日：2014-09-11
• US9150522B2
  申请人：——

  公开号：US9150522B2

  公开（公告）日：2015-10-06