N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)thiophene-2-sulfonamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)thiophene-2-sulfonamide
• 英文别名: N-(2,2-dimethyl-3-oxo-4H-pyrido[3,2-b][1,4]oxazin-7-yl)thiophene-2-sulfonamide
• 化学式: C₁₃H₁₃N₃O₄S₂
• 分子量: 339.396
• InChiKey: HXEPGWVDOSKUBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 在 吡啶 、 硫酸 、 palladium on carbon 、 氢气 、 硝酸 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 N-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)thiophene-2-sulfonamide
  参考文献：
  名称：

  Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer

  摘要：

  Prostate cancer is a commonly diagnosed cancer and a leading cause of cancer-related deaths. The bromodomain and extra terminal domain (BET) family proteins have emerged as potential therapeutic targets for the treatment of castration resistant prostate cancer. A series of 2,2-dimethy1-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC50 values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds 36 (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In in vivo studies, 36 demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development.

  DOI：

  10.1021/acsmedchemlett.8b00003

文献信息

• Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer
  作者：Qiuping Xiang、Yan Zhang、Jiaguo Li、Xiaoqian Xue、Chao Wang、Ming Song、Cheng Zhang、Rui Wang、Chenchang Li、Chun Wu、Yulai Zhou、Xiaohong Yang、Guohui Li、Ke Ding、Yong Xu

  DOI：10.1021/acsmedchemlett.8b00003

  日期：2018.3.8

  Prostate cancer is a commonly diagnosed cancer and a leading cause of cancer-related deaths. The bromodomain and extra terminal domain (BET) family proteins have emerged as potential therapeutic targets for the treatment of castration resistant prostate cancer. A series of 2,2-dimethy1-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC50 values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds 36 (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In in vivo studies, 36 demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development.