4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine | 1075756-61-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine
• 英文别名: 4-(2,6-Dichloro-5-fluoropyrimidin-4-yl)morpholine
• CAS: 1075756-61-4
• 化学式: C₈H₈Cl₂FN₃O
• 分子量: 252.075
• InChiKey: BEEVFQMKUBLZAW-UHFFFAOYSA-N

物化性质

• 沸点：
  392.7±42.0 °C(Predicted)
• 密度：
  1.506±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 生成 5-fluoro-N4-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N2-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-ylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Discovery of novel Jak2–Stat pathway inhibitors with extended residence time on target

  摘要：

  The discovery of the activating mutation V617F in the JH2 domain of Jak2 and the modulation of oncogenic Stat3 by Jak2 inhibitors have spurred a great interest in the inhibition of the Jak2/Stat pathway in oncology. In this Letter, we communicate the discovery of novel inhibitors of the Jak2/Stat5 axis, the N-(1H-pyrazol-3-yl)pyrimidin-2-amino derivatives. The rationale, synthesis and biological evaluation of these derivatives are reported. Two lead analogs from this series, 6 and 9, displayed prolonged residence time on Jak2, at enzymatic level. Although 6 and 9 exhibited moderate selectivity in a selected kinase panel, we chose to test these inhibitors in vivo as a consequence to their long residence time. However, extended inhibition of Jak2 due to the long residence time, in the form of inhibiting phosphorylation of downstream Stat5, was not recapitulated in an in vivo setting. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.111
• 作为产物：
  描述：

  吗啉 、 2,4,6-三氯-5-氟嘧啶 在 水 、 二氯甲烷 、 乙醇 作用下， 以 乙醇 为溶剂， 反应 3.5h， 以to give the title compound (2.0 g, 53%)的产率得到4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine
  参考文献：
  名称：

  Pyridin-2(1 H)-one derivatives as JAK inhibitors

  摘要：

  本发明公开了具有化学结构式（I）的新吡啶-2（1H）-酮衍生物，以及其制备方法、包含它们的药物组合物和它们作为Janus激酶（JAK）抑制剂在治疗中的应用。

  公开号：

  US09034311B2

文献信息

• [EN] PYRIDIN-2(1H)-ONE DERIVATIVES AS JAK INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDIN-2(1H)-ONE EN TANT QU'INHIBITEURS DE JAK
  申请人：ALMIRALL SA

  公开号：WO2013017461A1

  公开（公告）日：2013-02-07

  New pyridin-2(1H)-one derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  揭示了具有化学结构为式(I)的新吡啶-2(1H)-酮衍生物；以及它们的制备方法、包含它们的药物组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的应用。
• AMINO-THIAZOLYL-PYRIMIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
  申请人：Almeida Lynsie

  公开号：US20100204231A1

  公开（公告）日：2010-08-12

  The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These compounds provide a treatment for myeloproliferative disorders and cancer.

  本发明涉及式(I)的化合物及其制药组合物和使用方法。这些化合物提供了治疗骨髓增生性疾病和癌症的治疗方法。
• WO2008/135786
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/132502
  申请人：——

  公开号：——

  公开（公告）日：——
• Replacement of pyrazol-3-yl amine hinge binder with thiazol-2-yl amine: Discovery of potent and selective JAK2 inhibitors
  作者：Stephanos Ioannidis、Michelle L. Lamb、Lynsie Almeida、Huiping Guan、Bo Peng、Geraldine Bebernitz、Kirsten Bell、Marat Alimzhanov、Michael Zinda

  DOI：10.1016/j.bmcl.2010.01.091

  日期：2010.3

  Thiazol-2-yl amine was identified as an isosteric replacement for pyrazol-3-yl amine during our efforts to identify potent and selective JAK2 inhibitors. The rationale, synthesis and biological evaluation of several analogs is reported, along with the in vivo evaluation of the lead compounds. (C) 2010 Elsevier Ltd. All rights reserved.