2-[1-[(3-chloro-2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one | 1446359-27-8

• 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: 2-[1-[(3-chloro-2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one
• CAS: 1446359-27-8
• 化学式: C₁₇H₁₀ClF₂N₅O₂
• 分子量: 389.749
• InChiKey: CZQLBQGCAVFYDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 3-(dimethylamino)-2-fluoroacrylate 、 1-(3-chloro-2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazole-3-carboximidamide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 为溶剂， 反应 44.0h， 以38%的产率得到2-[1-[(3-chloro-2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one
  参考文献：
  名称：

  [EN] 2 - BENZYL, 3 - (PYRIMIDIN- 2 -YL) SUBSTITUTED PYRAZOLES USEFUL AS SGC STIMULATORS
  [FR] PYRAZOLES 2-BENZYLE, 3-(PYRIMIDIN-2-YLE)-SUBSTITUÉS UTILES COMME STIMULATEURS DE SCG

  摘要：

  描述了2-苄基，3-（嘧啶-2-基）取代的吡唑啉。它们可作为sGC的刺激剂，特别是NO-独立的、血红蛋白依赖的刺激剂。这些化合物可能对治疗、预防或管理本文披露的各种疾病有用。

  公开号：

  WO2013101830A1

文献信息

• 2-BENZYL, 3-(PYRIMIDIN-2-YL) SUBSTITUTED PYRAZOLES USEFUL AS SGC STIMULATORS
  申请人：IRONWOOD PHARMACEUTICALS, INC.

  公开号：US20150342954A1

  公开（公告）日：2015-12-03

  Compound of Table 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.

  表格I中的化合物被描述。它们可作为sGC的刺激剂，特别是NO独立的、血红素依赖性的刺激剂。这些化合物可能有助于治疗、预防或管理本文所披露的各种疾病。
• 2-[1-[(2-FLUOROPHENYL)METHYL]-5-(3-ISOXAZOLYL)-1H-PYRAZOL-3-YL]-PYRIMIDINE DERIVATIVES AND RELATED COMPOUNDS AS SOLUBLE GUANYLATE CYCLASE (SGC) STIMULATORS FOR THE TREATMENT OF PULMONARY HYPERTENSION
  申请人：Ironwood Pharmaceuticals, Inc.

  公开号：EP3112363A1

  公开（公告）日：2017-01-04

  2-[1-[(2-Fluorophenyl)methyl]-5-(3-isoxazolyl)-1H-pyrazol-3-yl]-pyrimidine derivatives and related compounds as soluble guanylate cyclase (sGC) stimulators, particularly NO-independent, heme-dependent stimulators, for treating pulmonary hypertension and other diseases.

  2-[1-[(2-氟苯基)甲基]-5-(3-异恶唑基)-1H-吡唑-3-基]-嘧啶衍生物及相关化合物，作为可溶性鸟苷酸环化酶（sGC）刺激剂，特别是 NO 依赖性、血红素依赖性刺激剂，用于治疗肺动脉高压和其他疾病。
• Discovery of IWP-051, a Novel Orally Bioavailable sGC Stimulator with Once-Daily Dosing Potential in Humans
  作者：Takashi Nakai、Nicholas R. Perl、Timothy C. Barden、Andrew Carvalho、Angelika Fretzen、Peter Germano、G-Yoon J. Im、Hong Jin、Charles Kim、Thomas W.-H. Lee、Kimberly Long、Joel Moore、Jason M. Rohde、Renee Sarno、Chrissie Segal、Erik O. Solberg、Jenny Tobin、Daniel P. Zimmer、Mark G. Currie

  DOI：10.1021/acsmedchemlett.5b00479

  日期：2016.5.12

  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.
• 2-benzyl-3-(oxazole/thiazole)-5-(pyrimidin-2-yl)-1(H)-pyrazole derivatives as stimulators of the soluble guanylate cyclase (sGC) for the treatment of e.g. hypertension or heart failure
  申请人：Ironwood Pharmaceuticals, Inc.

  公开号：EP2797915B1

  公开（公告）日：2016-07-13
• US9139564B2
  申请人：——

  公开号：US9139564B2

  公开（公告）日：2015-09-22