3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)aniline | 884603-40-1

• 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: 3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)aniline
• 英文别名: 3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)benzenamine；3-pyrrolidin-1-ylmethyl-5-trifluoromethyl-phenylamine
• CAS: 884603-40-1
• 化学式: C₁₂H₁₅F₃N₂
• 分子量: 244.26
• InChiKey: CDSYEKKBUORRBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)aniline 、 4-methyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以40.5%的产率得到4-methyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)-N-[3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]benzamide
  参考文献：
  名称：

  Discovery and Optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors

  摘要：

  Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)-benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a K-d value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.

  DOI：

  10.1021/jm301824k
• 作为产物：
  描述：

  3-硝基-5-(三氟甲基)苯甲酸 在 草酰氯 、 5%-palladium/activated carbon 、 氢气 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 8.5h， 生成 3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)aniline
  参考文献：
  名称：

  [EN] PYRAZOLE DERIVATIVES AS C-ABL INHIBITORS
  [FR] DÉRIVÉS DE PYRAZOLE EN TANT QU'INHIBITEURS DE C-ABL

  摘要：

  本发明涉及式（I）的化合物，该化合物是c-ABL的抑制剂。本发明还涉及包括这些化合物的制药组合物，以及它们在治疗或预防抑制c-ABL有益的医疗状况方面的应用。这些医疗状况包括神经退行性疾病和癌症。

  公开号：

  WO2022129915A1

文献信息

• Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors
  作者：Zhen Wang、Yali Zhang、Sergio G. Bartual、Jinfeng Luo、Tingting Xu、Wenting Du、Qiuju Xun、Zhengchao Tu、Rolf A. Brekken、Xiaomei Ren、Alex N. Bullock、Guang Liang、Xiaoyun Lu、Ke Ding

  DOI：10.1021/acsmedchemlett.6b00497

  日期：2017.3.9

  Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively

  急性肺损伤（ALI）是严重肺部炎症的致命症状。Discoidin域受体1（DDR1）是消炎药发现的新潜在靶标。发现一种新的基于选择性四氢异喹啉-7-羧酰胺的DDR1抑制剂7ae可以紧密结合DDR1蛋白并有效抑制其激酶功能，其Kd值为2.2 nM，IC50值为6.6 nM。该化合物剂量依赖性地抑制了脂多糖（LPS）诱导的白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）在小鼠原发性腹膜巨噬细胞（MPM）中的释放。此外，7ae在LPS诱导的小鼠ALI模型中还显示出有希望的体内抗炎作用。据我们所知，这是第一个“概念证明”
• Heteroaryl-substituted alkyne compounds and method of use
  申请人：Chaffee C. Stuart

  公开号：US20060217380A1

  公开（公告）日：2006-09-28

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , R 1 and R 2 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一种新型化合物类别，可用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关病症。该化合物具有一般式I，其中A1、A2、A3、A4、R1和R2如本文所定义。因此，本发明还涉及包含本发明化合物的制药组合物，使用本发明化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备本发明化合物的中间体和过程。
• Bicyclic compounds with kinase inhibitory activity
  申请人：Calderwood F. Emily

  公开号：US20070149533A1

  公开（公告）日：2007-06-28

  The present invention provides novel bicyclic compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种新颖的双环化合物，可用作蛋白激酶抑制剂。本发明还提供了包括本发明化合物的制药组合物以及使用该组合物治疗各种疾病的方法。
• Protein Kinase Inhibitors and Methods for Using Thereof
  申请人：Huang Shenlin

  公开号：US20100184765A1

  公开（公告）日：2010-07-22

  The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, and methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of Alk, Abl, Aurora-A, B-Raf, C-Raf, Bcr-Abl, BRK, Blk, Bmx, BTK, C-Kit, CSK, C-Src, EphB1, EphB2, EphB4, FLT1, Fms, Flt3, Fyn, FRK3, JAK2, KDR, Lck, Lyn, PDGFRα, PDGFRβ, PKCα, SAPK2α, Src, SIK, Syk, Tie2 and TrkB kinases.

  本发明提供了化合物及其药物组成物，可用作蛋白激酶抑制剂，并提供使用这些化合物治疗、缓解或预防与异常或失调激酶活性相关的疾病或症状的方法。在某些实施例中，本发明提供使用这些化合物治疗、缓解或预防涉及ALK、ABL、Aurora-A、B-Raf、C-Raf、Bcr-Abl、BRK、Blk、Bmx、BTK、C-Kit、CSK、C-Src、EphB1、EphB2、EphB4、FLT1、Fms、Flt3、Fyn、FRK3、JAK2、KDR、Lck、Lyn、PDGFRα、PDGFRβ、PKCα、SAPK2α、Src、SIK、Syk、Tie2和TrkB激酶异常激活的疾病或疾病的方法。
• NEW CHEMICAL COMPOUNDS
  申请人：Steurer Steffen

  公开号：US20110312939A1

  公开（公告）日：2011-12-22

  The present invention relates to new compounds of general formula (I), wherein the groups R 1 to R 3 , X 1 , X 2 , X 3 and L 1 are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof in such a treatment.

  本发明涉及一般式（I）的新化合物，其中R1至R3、X1、X2、X3和L1的基团如权利要求书所定义，适用于治疗以过度或异常细胞增殖为特征的疾病，并且本发明还涉及这些化合物在此类治疗中的使用。