[2-chloro-6-(morpholin-4-yl)pyrimidin-4-yl]methanol | 1101818-28-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: [2-chloro-6-(morpholin-4-yl)pyrimidin-4-yl]methanol
• 英文别名: (2-chloro-6-morpholinopyrimidin-4-yl)methanol；(2-chloro-6-morpholin-4-ylpyrimidin-4-yl)methanol
• CAS: 1101818-28-3
• 化学式: C₉H₁₂ClN₃O₂
• 分子量: 229.666
• InChiKey: CDLPYKPQNPJLMF-UHFFFAOYSA-N

物化性质

• 沸点：
  496.0±45.0 °C(Predicted)
• 密度：
  1.392±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-chloro-6-(morpholin-4-yl)pyrimidin-4-yl]methanol 在 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-amino-2-(2-chloro-6-morpholinopyrimidin-4-yl)benzo[b]thiophene 1,1-dioxide
  参考文献：
  名称：

  Expedient synthesis of biologically important sulfonylmethyl pyrimidines

  摘要：

  Two novel synthetic strategies that allow rapid diversification of the sulfone moiety in sulfonylmethyl pyrimidines, a class of compounds with a wide range of biological activity, which are of interest in a wide variety of drug discovery programmes, are described. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.04.111
• 作为产物：
  描述：

  methyl 2-chloro-6-morpholinopyrimidine-4-carboxylate 在 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以96%的产率得到[2-chloro-6-(morpholin-4-yl)pyrimidin-4-yl]methanol
  参考文献：
  名称：

  Expedient synthesis of biologically important sulfonylmethyl pyrimidines

  摘要：

  Two novel synthetic strategies that allow rapid diversification of the sulfone moiety in sulfonylmethyl pyrimidines, a class of compounds with a wide range of biological activity, which are of interest in a wide variety of drug discovery programmes, are described. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.04.111

文献信息

• Compounds - 945
  申请人：PIKE Kurt Gordon

  公开号：US20090018134A1

  公开（公告）日：2009-01-15

  A compound of formula (I) or a pharamaceutically acceptable salt 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.

  公式（I）的化合物或其药用盐，其制备方法，含有它们的药物组合物以及它们在治疗中的用途，例如在治疗增殖性疾病如癌症，特别是由mTOR激酶和/或一个或多个PI3K酶介导的疾病。
• 2-morpholin-4,6-disubstituted pyrimidine derivative, and preparation method and pharmaceutical use thereof
  申请人：Shanghai Haiyan Pharmaceutical Technology Co., Ltd.

  公开号：US10227324B2

  公开（公告）日：2019-03-12

  Disclosed is a 2-morpholin-4,6-disubstituted pyrimidine derivative as shown in formula (1) below, and a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof, and a pharmaceutical composition thereof and a use thereof, wherein the definition of each group is as shown in the description. The compound has a PI3K kinase inhibition activity, and has a relatively high inhibitive ability and a low cytotoxicity against PIK3CA mutant breast cancer cell strains T47D and MCF-7.

  公开了一种如下式（1）所示的2-吗啉-4,6-二取代嘧啶衍生物及其药学上可接受的盐、溶液剂、立体异构体或原药，以及其药物组合物及其用途，其中各基团的定义如说明书所示。该化合物具有 PI3K 激酶抑制活性，对 PIK3CA 突变乳腺癌细胞株 T47D 和 MCF-7 具有相对较高的抑制能力和较低的细胞毒性。
• [EN] 2-MORPHOLIN-4,6-DISUBSTITUTED PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF<br/>[FR] DÉRIVÉ DE PYRIMIDINE DISUBSTITUÉ EN 2-MORPHOLIN-4,6 ET PROCÉDÉ DE PRÉPARATION ET UTILISATION PHARMACEUTIQUE ASSOCIÉS<br/>[ZH] 2-吗啉-4,6-二取代的嘧啶衍生物、其制法与医药上的用途
  申请人：SHANGHAI HAIYAN PHARMACEUTICAL TECHNOLOGY CO LTD

  公开号：WO2016095833A1

  公开（公告）日：2016-06-23

  一种如下式(I)所示的2-吗啉-4,6-二取代的嘧啶衍生物、其药学上可接受的盐、溶剂化物、立体异构体或其前药，其药物组合物及其应用，其中各基团定义如说明书中所示。所述化合物具有PI3K激酶抑制活性，对PIK3CA突变型乳腺癌细胞株T47D和MCF-7具有较高的抑制性和低细胞毒性。
• Discovery of 4-{4-[(3<i>R</i>)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1<i>H</i>-indole (AZ20): A Potent and Selective Inhibitor of ATR Protein Kinase with Monotherapy in Vivo Antitumor Activity
  作者：Kevin M. Foote、Kevin Blades、Anna Cronin、Shaun Fillery、Sylvie S. Guichard、Lorraine Hassall、Ian Hickson、Xavier Jacq、Philip J. Jewsbury、Thomas M. McGuire、J. Willem M. Nissink、Rajesh Odedra、Ken Page、Paula Perkins、Abid Suleman、Kin Tam、Pia Thommes、Rebecca Broadhurst、Christine Wood

  DOI：10.1021/jm301859s

  日期：2013.3.14

  ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo- or radiation sensitizers or as monotherapy in tumors addicted to particular DNA-repair pathways. We describe the discovery and synthesis of a series of sulfonylmorpholinopyrimidines that show potent and selective ATR inhibition. Optimization from a high quality screening hit within tight SAR space led to compound 6 (AZ20) which inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 of 50 nM. Compound 6 potently inhibits the growth of LoVo colorectal adenocarcinoma tumor cells in vitro and has high free exposure in mouse following moderate oral doses. At well tolerated doses 6 leads to significant growth inhibition of LoVo xenografts grown in nude mice. Compound 6 is a useful compound to explore ATR pharmacology in vivo.
• 2-MORPHOLIN-4,6-DISUBSTITUTED PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF
  申请人：Shanghai Haiyan Pharmaceutical Technology Co., Ltd.

  公开号：EP3235816B1

  公开（公告）日：2020-02-12