5-bromo-1-(methoxymethyl)pyridin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-bromo-1-(methoxymethyl)pyridin-2(1H)-one
• 英文别名: 5-Bromo-1-(methoxymethyl)pyridin-2-one
• 化学式: C₇H₈BrNO₂
• 分子量: 218.05
• InChiKey: AEUIDNXOCVZNKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(methoxymethyl)pyridin-2(1H)-one 、 1-丁炔基三甲基硅烷 在 N,N-二甲基乙酰胺 、 palladium diacetate 、 caesium carbonate 作用下， 以71%的产率得到5-(but-1-yn-1-yl)-1-(methoxymethyl)pyridin-2(1H)-one
  参考文献：
  名称：

  Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts

  摘要：

  Approximately 80% of breast cancers are estrogen receptor alpha, (ER-a) positive, and although women typically initially respond, well to antihormonal therapies such as tamoxifen and aromatase inhibitors, resistance often emerges. Although a variety of resistance mechanism may be at play in this state, there is evidence that in many cases the ER still plays a central role, including mutations in the ER leading to constitutively active receptor. Fulvestrant is a steroid-based, selective estrogen receptor degrader., (SEED) That both antagonizes and degrades ER-alpha and is active in patients who have progressed on antihormonal agents. However, fulvestrant suffers from poor pharmaceutical properties and must be administered by intramuscular injections that limit the total amount of drug that can be administered and hence lead to the potential for incomplete receptor blockade. We describe the identification and characterization of a series of small-molecule, orally bioavailable SERDs, which are potent antagonists and degraders of ER-alpha and in which the ER-alpha degrading properties were prospectively optimized. The lead compound 111 (GDC-0810 or ARN-810) demonstrates robust activity in models of tamoxifen-sensitive and tamoxifen-resistant breast cancer, and is currently in clinical trials in women with locally advanced or metastatic estrogen receptor-positive breast cancer.

  DOI：

  10.1021/acs.jmedchem.5b00054
• 作为产物：
  描述：

  2-羟基-5-溴吡啶 、 氯甲基甲基醚 在 sodium hydride 作用下， 以40%的产率得到5-bromo-1-(methoxymethyl)pyridin-2(1H)-one
  参考文献：
  名称：

  Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts

  摘要：

  Approximately 80% of breast cancers are estrogen receptor alpha, (ER-a) positive, and although women typically initially respond, well to antihormonal therapies such as tamoxifen and aromatase inhibitors, resistance often emerges. Although a variety of resistance mechanism may be at play in this state, there is evidence that in many cases the ER still plays a central role, including mutations in the ER leading to constitutively active receptor. Fulvestrant is a steroid-based, selective estrogen receptor degrader., (SEED) That both antagonizes and degrades ER-alpha and is active in patients who have progressed on antihormonal agents. However, fulvestrant suffers from poor pharmaceutical properties and must be administered by intramuscular injections that limit the total amount of drug that can be administered and hence lead to the potential for incomplete receptor blockade. We describe the identification and characterization of a series of small-molecule, orally bioavailable SERDs, which are potent antagonists and degraders of ER-alpha and in which the ER-alpha degrading properties were prospectively optimized. The lead compound 111 (GDC-0810 or ARN-810) demonstrates robust activity in models of tamoxifen-sensitive and tamoxifen-resistant breast cancer, and is currently in clinical trials in women with locally advanced or metastatic estrogen receptor-positive breast cancer.

  DOI：

  10.1021/acs.jmedchem.5b00054

文献信息

• Pyridinone derivatives and their use as selective ALK-2 inhibitors
  申请人：NOVARTIS AG

  公开号：US11160797B2

  公开（公告）日：2021-11-02

  The invention relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明涉及一种式 I 的化合物或其药学上可接受的盐、一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药理活性剂的组合物和一种药物组合物。
• PYRIDINONE DERIVATIVES AND THEIR USE AS SELECTIVE ALK-2 INHIBITORS
  申请人：Novartis AG

  公开号：EP3713927B1

  公开（公告）日：2021-12-15
• Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts
  作者：Andiliy Lai、Mehmet Kahraman、Steven Govek、Johnny Nagasawa、Celine Bonnefous、Jackie Julien、Karensa Douglas、John Sensintaffar、Nhin Lu、Kyoung-jin Lee、Anna Aparicio、Josh Kaufman、Jing Qian、Gang Shao、Rene Prudente、Michael J. Moon、James D. Joseph、Beatrice Darimont、Daniel Brigham、Kate Grillot、Richard Heyman、Peter J. Rix、Jeffrey H. Hager、Nicholas D. Smith

  DOI：10.1021/acs.jmedchem.5b00054

  日期：2015.6.25

  Approximately 80% of breast cancers are estrogen receptor alpha, (ER-a) positive, and although women typically initially respond, well to antihormonal therapies such as tamoxifen and aromatase inhibitors, resistance often emerges. Although a variety of resistance mechanism may be at play in this state, there is evidence that in many cases the ER still plays a central role, including mutations in the ER leading to constitutively active receptor. Fulvestrant is a steroid-based, selective estrogen receptor degrader., (SEED) That both antagonizes and degrades ER-alpha and is active in patients who have progressed on antihormonal agents. However, fulvestrant suffers from poor pharmaceutical properties and must be administered by intramuscular injections that limit the total amount of drug that can be administered and hence lead to the potential for incomplete receptor blockade. We describe the identification and characterization of a series of small-molecule, orally bioavailable SERDs, which are potent antagonists and degraders of ER-alpha and in which the ER-alpha degrading properties were prospectively optimized. The lead compound 111 (GDC-0810 or ARN-810) demonstrates robust activity in models of tamoxifen-sensitive and tamoxifen-resistant breast cancer, and is currently in clinical trials in women with locally advanced or metastatic estrogen receptor-positive breast cancer.