6-((methylsulfonyl)methyl)pyrimidine-2,4-(1H,3H)-dione | 944058-91-7

• 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: 6-((methylsulfonyl)methyl)pyrimidine-2,4-(1H,3H)-dione
• 英文别名: 6-(methylsulfonylmethyl)-1H-pyrimidine-2,4-dione
• CAS: 944058-91-7
• 化学式: C₆H₈N₂O₄S
• 分子量: 204.207
• InChiKey: QDUCJSGZWMZJAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-((methylsulfonyl)methyl)pyrimidine-2,4-(1H,3H)-dione 在 N-甲基吡咯烷酮 、 1-氯乙基氯甲酸酯 、 四丁基溴化铵 、 sodium hydride 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 22.5h， 生成 4-(2-chloro-6-(4-(methylsulfonyl)piperidin-4-yl)pyrimidin-4-yl)morpholine
  参考文献：
  名称：

  Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): A Potent and Selective Inhibitor of ATR Protein Kinase with Monotherapy in Vivo Antitumor Activity

  摘要：

  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.

  DOI：

  10.1021/jm301859s
• 作为产物：
  描述：

  6-(氯甲基)脲嘧啶 、 sodium methansulfinate 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以to give the desired material as a yellow solid (12.72 g)的产率得到6-((methylsulfonyl)methyl)pyrimidine-2,4-(1H,3H)-dione
  参考文献：
  名称：

  MORPHOLINO PYRIMIDINE DERIVATIVES USEFUL IN THE TREATMENT OF PROLIFERATIVE DISORDERS

  摘要：

  化合物式(I)或其药学上可接受的盐，其制备方法，包含它们的制药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中，特别是在由mTOR激酶和/或一个或多个PI3K酶介导的疾病中。

  公开号：

  US20090325957A1

文献信息

• [EN] PYRIDYL OR PYRIMIDYL MTOR KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE MTOR DE PYRIDYLE OU DE PYRIMIDYLE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2020249652A1

  公开（公告）日：2020-12-17

  The invention relates to compounds or pharmaceutically acceptable salts thereof of formula (I): (I) wherein R1, R2, R3, R4, R4' and R5 are as defined in the description and claims; and compounds or pharmaceutically acceptable salts thereof of formulas (II), (IIa), (IIb), (IIc), and (III) having mTOR kinase inhibitor activity. The invention also relates to pharmaceutical compositions which include a compound of formula (I), (II), (IIa), (IIb), (IIc), or (III) or a pharmaceutically acceptable salt thereof, and to the use of a compound of formula (I), (II), (IIa), (IIb), (IIc), or (III), or a pharmaceutically acceptable salt thereof in therapy, including in the treatment of a disease or condition for which an mTOR kinase inhibitor activity is indicated, and in particular the treatment of idiopathic pulmonary fibrosis.

  该发明涉及化合物或其药用可接受盐的公式(I)：（I）其中R1、R2、R3、R4、R4'和R5如描述和索赔中定义；以及具有mTOR激酶抑制剂活性的公式(II)、(IIa)、(IIb)、(IIc)和(III)的化合物或其药用可接受盐。该发明还涉及包括公式(I)、(II)、(IIa)、(IIb)、(IIc)或(III)的化合物或其药用可接受盐的药物组合物，以及在治疗中使用公式(I)、(II)、(IIa)、(IIb)、(IIc)或(III)的化合物或其药用可接受盐，包括治疗需要mTOR激酶抑制剂活性的疾病或症状，特别是治疗特发性肺纤维化。
• [EN] PYRIMIDINE INDOLE DERIVATIVES FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE PYRIMIDINE ET D'INDOLE POUR LE TRAITEMENT DU CANCER
  申请人：ASTRAZENECA AB

  公开号：WO2010073034A1

  公开（公告）日：2010-07-01

  There is provided pyrimidinyl indole compounds of Formula (I), or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly for treating cancer.

  提供了式（I）的嘧啶基吲哚化合物，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应用，特别是用于治疗癌症。
• 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。
• [EN] MORPHOLINO PYRIMIDINE DERIVATIVES USED IN DISEASES LINKED TO MTOR KINASE AND/OR PI3K<br/>[FR] DÉRIVÉS DE MORPHOLINO PYRIMIDINE UTILISÉS DANS DES MALADIES LIÉES À UNE KINASE MTOR ET/OU À PI3K
  申请人：ASTRAZENECA AB

  公开号：WO2009007750A1

  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.

  化合物式(I)或其药学上可接受的盐，其制备方法，含有它们的药物组合物以及它们在治疗中的应用，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酶介导的疾病中的使用。
• MORPHOLINO PYRIMIDINE DERIVATIVES USEFUL IN THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Finlay Maurice Raymond Verschoyle

  公开号：US20090325957A1

  公开（公告）日：2009-12-31

  A compound of formula (I) or a pharmaceutically 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.

  化合物式(I)或其药学上可接受的盐，其制备方法，包含它们的制药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中，特别是在由mTOR激酶和/或一个或多个PI3K酶介导的疾病中。