5-fluoro-2-[1-[(3-fluorothiophen-2-yl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1579999-89-5

• 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: 5-fluoro-2-[1-[(3-fluorothiophen-2-yl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one
• CAS: 1579999-89-5
• 化学式: C₁₅H₉F₂N₅O₂S
• 分子量: 361.332
• InChiKey: SDWIWEAJPNCSAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  sodium (E)-3-ethoxy-2-fluoro-3-oxoprop-1-en-1-olate 、 1-((3-fluorothiophen-2-yl)methyl)-5-(isoxazol-3-yl)-1H-pyrazole-3-carboximidamide 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 反应 16.0h， 以33%的产率得到5-fluoro-2-[1-[(3-fluorothiophen-2-yl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one
  参考文献：
  名称：

  Discovery of IWP-051, a Novel Orally Bioavailable sGC Stimulator with Once-Daily Dosing Potential in Humans

  摘要：

  In recent years, soluble guanylate cyclase (sGC, EC 4.6.1.2) has emerged as an attractive therapeutic target for treating cardiovascular diseases and diseases associated with fibrosis and end-organ failure. Herein, we describe our design and synthesis of a series of 4-hydroxypyrimidine sGC stimulators starting with an internally discovered lead. Our efforts have led to the discovery of IWP-051, a molecule that achieves good alignment of potency, stability, selectivity, and pharmacodynamic effects while maintaining favorable pharmacokinetic properties with once-daily dosing potential in humans.

  DOI：

  10.1021/acsmedchemlett.5b00479

文献信息

• [EN] SGC STIMULATORS<br/>[FR] STIMULATEURS DE LA SGC
  申请人：IRONWOOD PHARMACEUTICALS INC

  公开号：WO2014047111A1

  公开（公告）日：2014-03-27

  Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.

  描述了式I的化合物。它们可作为sGC的刺激剂，特别是独立于NO的、依赖血红素的刺激剂。这些化合物可能对治疗、预防或管理本文中披露的各种疾病有用。
• sGC STIMULATORS
  申请人：IM G-Yoon Jamie

  公开号：US20150274712A1

  公开（公告）日：2015-10-01

  Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.
• US9309235B2
  申请人：——

  公开号：US9309235B2

  公开（公告）日：2016-04-12