5-[(2-chloro-6-fluorophenyl)carbamoyl]-2-N-(4-morpholinophenyl)-4-N-[(tetrahydrofuran-2-yl)methyl]pyrimidine-2,4-diamine

• 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: 5-[(2-chloro-6-fluorophenyl)carbamoyl]-2-N-(4-morpholinophenyl)-4-N-[(tetrahydrofuran-2-yl)methyl]pyrimidine-2,4-diamine
• 英文别名: N-(2-chloro-6-fluorophenyl)-2-(4-morpholinophenylamino)-4-((tetrahydrofuran-2-yl)methylamino)pyrimidine-5-carboxamide；N-(2-chloro-6-fluorophenyl)-2-(4-morpholin-4-ylanilino)-4-(oxolan-2-ylmethylamino)pyrimidine-5-carboxamide
• 化学式: C₂₆H₂₈ClFN₆O₃
• 分子量: 526.998
• InChiKey: OIMQRVNFJOBBFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,4-二氯-5-嘧啶甲酰氯 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇甲醚 为溶剂， 反应 31.67h， 生成 5-[(2-chloro-6-fluorophenyl)carbamoyl]-2-N-(4-morpholinophenyl)-4-N-[(tetrahydrofuran-2-yl)methyl]pyrimidine-2,4-diamine
  参考文献：
  名称：

  [EN] INHIBITORS OF ACK1/TNK2 TYROSINE KINASE
  [FR] INHIBITEURS DE LA TYROSINE KINASE ACK1/TNK2

  摘要：

  描述了癌症治疗和抗癌化合物。特别是，披露了Ack1酪氨酸激酶的抑制剂及其在癌症治疗中的应用。还披露了筛选新的Ack1酪氨酸激酶抑制剂的方法。在具体示例中，披露了具有I至IV式的化合物。

  公开号：

  WO2015021149A1

文献信息

• [EN] INHIBITORS OF ACK1/TNK2 TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE ACK1/TNK2
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2015021149A1

  公开（公告）日：2015-02-12

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are ihibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specifc example, compound having Formula I through IV are disclosed.

  描述了癌症治疗和抗癌化合物。特别是，披露了Ack1酪氨酸激酶的抑制剂及其在癌症治疗中的应用。还披露了筛选新的Ack1酪氨酸激酶抑制剂的方法。在具体示例中，披露了具有I至IV式的化合物。
• INHIBITORS OF ACK1/TNK2 TYROSINE KINASE
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20160176826A1

  公开（公告）日：2016-06-23

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.

  本文描述了癌症治疗和抗癌化合物。特别地，揭示了Ack1酪氨酸激酶抑制剂及其在癌症治疗中的应用。还披露了筛选新的Ack1酪氨酸激酶抑制剂的方法。具体例子中，揭示了具有I至IV式的化合物。
• Inhibitors of ACK1/TNK2 tyrosine kinase
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US10017478B2

  公开（公告）日：2018-07-10

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.

  所述的是癌症疗法和抗癌化合物。 特别是公开了 Ack1 酪氨酸激酶的抑制剂及其在治疗癌症中的用途。 还公开了筛选新的Ack1酪氨酸激酶抑制剂的方法。 在具体实例中，公开了具有式I至式IV的化合物。
• US9850216B2
  申请人：——

  公开号：US9850216B2

  公开（公告）日：2017-12-26
• Development of Novel ACK1/TNK2 Inhibitors Using a Fragment-Based Approach
  作者：Harshani R. Lawrence、Kiran Mahajan、Yunting Luo、Daniel Zhang、Nathan Tindall、Miles Huseyin、Harsukh Gevariya、Sakib Kazi、Sevil Ozcan、Nupam P. Mahajan、Nicholas J. Lawrence

  DOI：10.1021/jm501929n

  日期：2015.3.26

  The tyrosine kinase ACK1, a critical signal transducer regulating survival of hormone-refractory cancers, is an important therapeutic target, for which there are no selective inhibitors in clinical trials to date. This work reports the discovery of novel and potent inhibitors for ACK1 tyrosine kinase (also known as TNK2) using an innovative fragment-based approach. Focused libraries were designed and synthesized by selecting fragments from reported ACK inhibitors to create hybrid structures in a mix and match process. The hybrid library was screened by enzyme-linked immunosorbent assay-based kinase inhibition and P-33 HotSpot assays. Systematic structure-activity relationship studies led to the identification of compound (R)-9b, which shows potent in vitro (IC50 = 56 nM, n = 3, P-33 HotSpot assay) and in vivo (IC50 < 2 mu M, human cancer cell lines) ACK1 inhibition. Both (R)-9b and (S)-9b were stable in human plasma and displayed a long half-life (t(1/2) > 6 h).