6-[(propan-2-ylsulfanyl)methyl]pyrimidine-2,4(1H,3H)-dione | 1009627-60-4

• 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-[(propan-2-ylsulfanyl)methyl]pyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-[(isopropylthio)methyl]pyrimidine-2,4(1H,3H)-dione；6-(propan-2-ylsulfanylmethyl)-1H-pyrimidine-2,4-dione
• CAS: 1009627-60-4
• 化学式: C₈H₁₂N₂O₂S
• 分子量: 200.261
• InChiKey: MOASQACAGOFRRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-[(propan-2-ylsulfanyl)methyl]pyrimidine-2,4(1H,3H)-dione 在 四丁基溴化铵 、 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 、 三氯氧磷 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 43.0h， 生成 4-(2-chloro-6-(1-(isopropylsulfonyl)cyclopropyl)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 、 异丙硫醇 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 2.25h， 生成 6-[(propan-2-ylsulfanyl)methyl]pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Compounds - 945

  摘要：

  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。

  公开号：

  US20090018134A1

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。
• Transcutaneous immunostimulation
  申请人：Finlay Maurice Raymond Verschoyle

  公开号：US20080171743A1

  公开（公告）日：2008-07-17

  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.

  公式为（I）的化合物或其药学上可接受的盐，其制备过程，包含它们的制药组合物以及它们在治疗中的用途，例如在治疗增生性疾病如癌症和特别是由mTOR激酶和/或一个或多个PI3K酶介导的疾病中的用途。
• Azole derivatives as apelin receptor agonist
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：US10626096B2

  公开（公告）日：2020-04-21

  The present invention relates to a novel azole derivative as an apelin receptor agonist and a method for treating cardiovascular disease, diabetic disease, renal disease, hypertension, and arteriosclerosis, etc., using the same. The present invention provides a compound represented by formula (I) or a pharmacologically acceptable salt thereof wherein X1 represents —NH═ or —CH═, X2 represents —CH═ or —N═, R1 and R2 each represent a C1 to C6 alkoxy group or the like, R3 represents a heteroaryl group (the heteroaryl group is optionally substituted by a methyl group or the like) or the like, and R4 represents a C1 to C6 alkylthio group or a C2 to C6 alkenyl group (the C1 to C6 alkylthio group and the C2 to C6 alkenyl group are each optionally substituted by one carboxy group or the like) or the like.

  本发明涉及一种作为芹菜素受体激动剂的新型唑衍生物以及用其治疗心血管疾病、糖尿病疾病、肾脏疾病、高血压和动脉硬化等的方法。本发明提供了由式（I）代表的化合物或其药理上可接受的盐 其中 X1 代表-NH═或-CH═，X2 代表-CH═或-N═，R1 和 R2 各自代表 C1 至 C6 烷氧基或类似物、R3 代表杂芳基（杂芳基可选择被甲基或类似基团取代）或类似基团，R4 代表 C1 至 C6 烷硫基或 C2 至 C6 烯基（C1 至 C6 烷硫基和 C2 至 C6 烯基各自可选择被一个羧基或类似基团取代）或类似基团。
• MORPHOLINO PYRIMIDINE DERIVATIVES USEFUL IN THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：AstraZeneca AB

  公开号：EP2057140B1

  公开（公告）日：2012-08-08
• TRISUBSTITUTED PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PROLIFERATIVE DISEASES
  申请人：AstraZeneca AB

  公开号：EP2074118A2

  公开（公告）日：2009-07-01