2-({4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}amino)ethanol | 457914-32-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 2-({4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}amino)ethanol
• 英文别名: 2-[[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]amino]ethanol
• CAS: 457914-32-8
• 化学式: C₁₉H₁₉FN₈O
• 分子量: 394.411
• InChiKey: BAGSFOMEHVONDA-UHFFFAOYSA-N

物化性质

• 沸点：
  609.9±55.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  草酸醛 、 2-({4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}amino)ethanol 以 水 为溶剂， 反应 12.0h， 生成 (9S,13S)-3-amino-5-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]-10-oxa-1,4,6,8-tetrazatricyclo[7.3.1.02,7]trideca-2,4,6-trien-13-ol
  参考文献：
  名称：

  Metabolites of Orally Active NO-Independent Pyrazolopyridine Stimulators of Soluble Guanylate Cyclase

  摘要：

  The pyrazolopyridine stimulators of soluble guanylate cyclase BAY 41-2272 and 41-8543 were oxidised in rats and dogs at their 5-pyrimidinyl-cyclopropyl and -morpholino residue. These metabolites activate the soluble guanylate cyclase, induce vaso-elaxation and thereby may contribute to the in vivo activity of BAY 41-2272 and BAY 41-8543. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00034-2
• 作为产物：
  描述：

  1-(2-氟苄基)-1H-吡唑并[3,4-b]吡啶-3-甲腈 在 镍 3 A molecular sieve 、 四丁基氟化铵 、 氢气 、 sodium methylate 、 sodium cyanoborohydride 、 氯化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~110.0 ℃ 、6.5 MPa 条件下， 反应 51.0h， 生成 2-({4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}amino)ethanol
  参考文献：
  名称：

  Metabolites of Orally Active NO-Independent Pyrazolopyridine Stimulators of Soluble Guanylate Cyclase

  摘要：

  The pyrazolopyridine stimulators of soluble guanylate cyclase BAY 41-2272 and 41-8543 were oxidised in rats and dogs at their 5-pyrimidinyl-cyclopropyl and -morpholino residue. These metabolites activate the soluble guanylate cyclase, induce vaso-elaxation and thereby may contribute to the in vivo activity of BAY 41-2272 and BAY 41-8543. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00034-2

文献信息

• Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure
  作者：Markus Follmann、Jens Ackerstaff、Gorden Redlich、Frank Wunder、Dieter Lang、Armin Kern、Peter Fey、Nils Griebenow、Walter Kroh、Eva-Maria Becker-Pelster、Axel Kretschmer、Volker Geiss、Volkhart Li、Alexander Straub、Joachim Mittendorf、Rolf Jautelat、Hartmut Schirok、Karl-Heinz Schlemmer、Klemens Lustig、Michael Gerisch、Andreas Knorr、Hanna Tinel、Thomas Mondritzki、Hubert Trübel、Peter Sandner、Johannes-Peter Stasch

  DOI：10.1021/acs.jmedchem.7b00449

  日期：2017.6.22

  The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.