4-(chloromethyl)-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine | 944058-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(chloromethyl)-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine
• 英文别名: 4-[6-(chloromethyl)-2-pyridin-2-ylpyrimidin-4-yl]morpholine
• CAS: 944058-85-9
• 化学式: C₁₄H₁₅ClN₄O
• 分子量: 290.752
• InChiKey: RGYKVGCIRFNCGL-UHFFFAOYSA-N

物化性质

• 沸点：
  420.9±45.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(chloromethyl)-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine 在 Selectfluor 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以20%的产率得到4-(chloromethyl)-5-fluoro-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine
  参考文献：
  名称：

  WO2007/80382

  摘要：

  公开号：
• 作为产物：
  描述：

  2-脒基吡啶盐酸盐 在 sodium hydride 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 4-(chloromethyl)-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine
  参考文献：
  名称：

  Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor

  摘要：

  High throughput screening to identify inhibitors of the mTOR kinase revealed sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound displayed good physicochemical properties and selectivity over related kinases such as PI3K alpha. Library preparation of related analogs allowed the establishment of additional SAR understanding and in particular the requirement for a key hydrogen bond donor motif at the 4-position of the phenyl ring in compounds such as indole 19. Isosteric replacement of the indole functionality led to the identification of urea compounds such as 32 that show good levels of mTOR inhibition in both enzyme and cellular assays. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.036

文献信息

• MORPHOLINO PYRIMIDINE DERIVATIVES AND THEIR USE IN THERAPY
  申请人：Dishington Allan Paul

  公开号：US20110034454A1

  公开（公告）日：2011-02-10

  A compound of formula (I) or a salt, ester or prodrug thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of proliferative disease such as cancer and particularly in disease mediated by an mTOR kinase and/or one or more PI3K enzyme.

  化合物的公式（I）或其盐、酯或前药，它们的制备过程，包含它们的药物组合物以及它们在治疗中的用途，例如在治疗增生性疾病如癌症中，特别是在由mTOR激酶和/或一个或多个PI3K酶介导的疾病中。
• [EN] MORPHOLINO PYRIMIDINE DERIVATIVES AND THEIR USE IN THERAPY<br/>[FR] DÉRIVÉS DE MORPHOLINOPYRIMIDINE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：ASTRAZENECA AB

  公开号：WO2007080382A1

  公开（公告）日：2007-07-19

  [EN] A compound of formula (I) or a salt, ester or prodrug thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of proliferative disease such as cancer and particularly in disease mediated by an mTOR kinase and/or one or more PI3K enzyme.
  [FR] L'invention concerne un composé de formule (I) ou un sel, ester ou promédicament de celui-ci, des procédés pour les préparer, des compositions pharmaceutiques les contenant, ainsi que leur utilisation thérapeutique, par exemple dans le traitement d'une maladie proliférative telle que le cancer et en particulier une maladie médiée par une mTOR kinase et/ou par une ou plusieurs enzymes PI3K.
• WO2007/80382
  申请人：——

  公开号：——

  公开（公告）日：——
• Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor
  作者：M. Raymond V. Finlay、David Buttar、Susan E. Critchlow、Allan P. Dishington、Shaun M. Fillery、Eric Fisher、Steve C. Glossop、Mark A. Graham、Trevor Johnson、Gillian M. Lamont、Simon Mutton、Paula Perkins、Kurt G. Pike、Anthony M. Slater.

  DOI：10.1016/j.bmcl.2012.04.036

  日期：2012.6

  High throughput screening to identify inhibitors of the mTOR kinase revealed sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound displayed good physicochemical properties and selectivity over related kinases such as PI3K alpha. Library preparation of related analogs allowed the establishment of additional SAR understanding and in particular the requirement for a key hydrogen bond donor motif at the 4-position of the phenyl ring in compounds such as indole 19. Isosteric replacement of the indole functionality led to the identification of urea compounds such as 32 that show good levels of mTOR inhibition in both enzyme and cellular assays. (C) 2012 Elsevier Ltd. All rights reserved.