8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidine-6-carboximidamide | 1426309-22-9

• 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: 8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidine-6-carboximidamide
• 英文别名: 8-(2-Fluorobenzyl)imidazo[1,5-a]pyrimidine-6-carboximidamide；8-[(2-fluorophenyl)methyl]imidazo[1,5-a]pyrimidine-6-carboximidamide
• CAS: 1426309-22-9
• 化学式: C₁₄H₁₂FN₅
• 分子量: 269.281
• InChiKey: IMCBPIXIXXIESA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  80.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidine-6-carboximidamide 在 二碘甲烷 、 potassium tert-butylate 、 亚硝酸异戊酯 作用下， 以 N-甲基吡咯烷酮 、 叔丁醇 为溶剂， 反应 24.5h， 生成 2-[8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidin-6-yl]-5,5-dimethyl-4-[(3,3,3-trifluoropropyl)amino]-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one
  参考文献：
  名称：

  Substituted annellated pyrimidines and use thereof

  摘要：

  本申请涉及新型取代的螺合嘧啶类化合物，其生产方法，单独或组合使用用于治疗和/或预防疾病以及用于生产治疗和/或预防疾病的药物产品的用途，特别是用于治疗和/或预防心血管疾病。

  公开号：

  US20130338137A1
• 作为产物：
  描述：

  2-amino-3-(2-fluorophenyl)propanenitrile 在 盐酸 、 sodium methylate 、 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidine-6-carboximidamide
  参考文献：
  名称：

  Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.7b00449

文献信息

• SUBSTITUIERTE ANNELLIERTE PYRIMIDINE UND IHRE VERWENDUNG
  申请人：Bayer Intellectual Property GmbH

  公开号：EP2751106B1

  公开（公告）日：2017-10-18
• US8859569B2
  申请人：——

  公开号：US8859569B2

  公开（公告）日：2014-10-14
• [DE] SUBSTITUIERTE ANNELLIERTE PYRIMIDINE UND IHRE VERWENDUNG<br/>[EN] SUBSTITUTED ANNELLATED PYRIMIDINE AND THE USE THEREOF<br/>[FR] PYRIMIDINES ANNELÉES SUBSTITUÉES ET LEUR UTILISATION
  申请人：BAYER IP GMBH

  公开号：WO2013030288A1

  公开（公告）日：2013-03-07

  Die vorliegende Anmeldung betrifft neue substituierte annellierte Pyrimidine, Verfahren zu ihrer Herstellung, ihre Verwendung allein oder in Kombinationen zur Behandlung und/oder Prophylaxe von Krankheiten sowie ihre Verwendung zur Herstellung von Arzneimitteln zur Behandlung und/oder Prophylaxe von Krankheiten, insbesondere zur Behandlung und/oder Prophylaxe von Herz-Kreislauf-Erkrankungen.
• 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.
• Substituted annellated pyrimidines and use thereof
  申请人：FOLLMANN Markus

  公开号：US20130338137A1

  公开（公告）日：2013-12-19

  The present application relates to novel substituted annellated pyrimidines, methods for production thereof, use thereof alone or in combinations for treating and/or preventing diseases and use thereof for the production of medicinal products for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.

  本申请涉及新型取代的螺合嘧啶类化合物，其生产方法，单独或组合使用用于治疗和/或预防疾病以及用于生产治疗和/或预防疾病的药物产品的用途，特别是用于治疗和/或预防心血管疾病。