ethyl-Nβ-[4-amino-2-methylthio-5-nitropyrimidin-6-yl],Nβ-[3′-(pyrrolidin-1″-ylmethyl)-benzyl]-β-alaninoate | 1228588-20-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl-Nβ-[4-amino-2-methylthio-5-nitropyrimidin-6-yl],Nβ-[3′-(pyrrolidin-1″-ylmethyl)-benzyl]-β-alaninoate
• 英文别名: Ethyl 3-[(6-amino-2-methylsulfanyl-5-nitropyrimidin-4-yl)-[[3-(pyrrolidin-1-ylmethyl)phenyl]methyl]amino]propanoate
• CAS: 1228588-20-2
• 化学式: C₂₂H₃₀N₆O₄S
• 分子量: 474.584
• InChiKey: NXGXNWVTPJPMPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl-Nβ-[4-amino-2-methylthio-5-nitropyrimidin-6-yl],Nβ-[3′-(pyrrolidin-1″-ylmethyl)-benzyl]-β-alaninoate 在 sodium tungstate (VI) dihydrate 、 双氧水 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 ethyl-Nβ-[4-amino-2-n-butoxy-5-nitropyrimidin-6-yl],Nβ-[3′-(pyrrolidin-1″-ylmethyl)-benzyl]-β-alaninoate
  参考文献：
  名称：

  Identification and Optimization of Pteridinone Toll-like Receptor 7 (TLR7) Agonists for the Oral Treatment of Viral Hepatitis

  摘要：

  Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading to the discovery of GS-9620. Analogues were optimized for the immunomodulatory activity and selectivity versus other TLRs, based on differential induction of key cytokines including interferon a (IFN-alpha) and tumor necrosis factor a (TNF-alpha). In addition, physicochemical properties were adjusted to achieve desirable in vivo pharmacokinetic and pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the treatment of chronic hepatitis B (HBV) infection.

  DOI：

  10.1021/jm400815m
• 作为产物：
  描述：

  beta-丙氨酸乙酯盐酸盐 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 1.25h， 生成 ethyl-Nβ-[4-amino-2-methylthio-5-nitropyrimidin-6-yl],Nβ-[3′-(pyrrolidin-1″-ylmethyl)-benzyl]-β-alaninoate
  参考文献：
  名称：

  Identification and Optimization of Pteridinone Toll-like Receptor 7 (TLR7) Agonists for the Oral Treatment of Viral Hepatitis

  摘要：

  Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading to the discovery of GS-9620. Analogues were optimized for the immunomodulatory activity and selectivity versus other TLRs, based on differential induction of key cytokines including interferon a (IFN-alpha) and tumor necrosis factor a (TNF-alpha). In addition, physicochemical properties were adjusted to achieve desirable in vivo pharmacokinetic and pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the treatment of chronic hepatitis B (HBV) infection.

  DOI：

  10.1021/jm400815m

文献信息

• MODULATORS OF TOLL-LIKE RECEPTORS
  申请人：Desai Manoj C.

  公开号：US20100143301A1

  公开（公告）日：2010-06-10

  Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

  提供了公式II的TLR调节剂：其药用盐，含有这类化合物的组合物，以及包括给予这类化合物的治疗方法。
• Modulators of toll-like receptors
  申请人：Gilead Sciences, Inc.

  公开号：US10172860B2

  公开（公告）日：2019-01-08

  Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

  所提供的是式 II 的 TLR 调节剂： 其药学上可接受的盐、含有此类化合物的组合物以及包括施用此类化合物的治疗方法。
• Intermediates for the preparation of modulators of toll-like receptors
  申请人：GILEAD SCIENCES, INC.

  公开号：EP2818469B1

  公开（公告）日：2017-02-15
• US8367670B2
  申请人：——

  公开号：US8367670B2

  公开（公告）日：2013-02-05
• US8629142B2
  申请人：——

  公开号：US8629142B2

  公开（公告）日：2014-01-14