ethyl 5-amino-4-(2-fluorobenzyl)-1H-imidazole-2-carboxylate | 1011528-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-amino-4-(2-fluorobenzyl)-1H-imidazole-2-carboxylate
• 英文别名: ethyl 4-amino-5-[(2-fluorophenyl)methyl]-1H-imidazole-2-carboxylate
• CAS: 1011528-06-5
• 化学式: C₁₃H₁₄FN₃O₂
• 分子量: 263.271
• InChiKey: FORRYBIXAGQRLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  81
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-amino-4-(2-fluorobenzyl)-1H-imidazole-2-carboxylate 在 盐酸 、 sodium methylate 、 氯化铵 、 三乙胺 、 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 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 2-[8-(2-fluorobenzyl)imidazo[1,5-a]pyrimidin-6-yl]-5-[(E)-phenyldiazenyl]pyrimidine-4,6-diamine
  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
• 作为产物：
  描述：

  2-氟溴苄 在 盐酸 、 potassium tert-butylate 、 四丁基碘化铵 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 水 为溶剂， 生成 ethyl 5-amino-4-(2-fluorobenzyl)-1H-imidazole-2-carboxylate
  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

• PYRAZOLOPYRIDINE, INDAZOLE, IMIDAZOPYRIDINE, IMIDAZOPYRIMIDINE, PYRAZOLOPYRAZINE AND PYRAZOLOPYRIDINE DERIVATIVES AS STIMULATORS OF GUANYLATE CYCLASE FOR CARDIOVASCULAR DISORDERS
  申请人：Schirok Hartmut

  公开号：US20100029653A1

  公开（公告）日：2010-02-04

  The present application relates to novel azabicyclic compounds, processes for their preparation, their use alone or in combinations for the treatment and/or prevention of diseases, and their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.

  本申请涉及新型氮杂双环化合物，其制备方法，它们单独或与其他物质结合用于治疗和/或预防疾病，以及用于生产治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管疾病。
• Pyrazolopyridine, indazole, imidazopyridine, imidazopyrimidine, pyrazolopyrazine and pyrazolopyridine derivatives as stimulators of guanylate cyclase for cardiovascular disorders
  申请人：Bayer Intellectual Property GmbH

  公开号：US08309551B2

  公开（公告）日：2012-11-13

  The present application relates to novel azabicyclic compounds, processes for their preparation, their use alone or in combinations for the treatment and/or prevention of diseases, and their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.

  本申请涉及新型杂环双环化合物、其制备过程，它们单独或组合使用用于治疗和/或预防疾病，以及它们用于制造治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管疾病。
• PYRAZOLOPYRIDIN, INDAZOL, IMIDAZOPYRIDIN, IMIDAZOPYRIMIDIN, PYRAZOLOPYRAZIN UND PYRAZOLOPYRIDIN DERIVATE ALS STIMULATOREN DER GUANYLATCYCLASE ZUR HERZ-KREISLAUFERKRANKUNGEN
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2066666A1

  公开（公告）日：2009-06-10
• US8309551B2
  申请人：——

  公开号：US8309551B2

  公开（公告）日：2012-11-13
• [DE] PYRAZOLOPYRIDIN, INDAZOL, IMIDAZOPYRIDIN, IMIDAZOPYRIMIDIN, PYRAZOLOPYRAZIN UND PYRAZOLOPYRIDIN DERIVATE ALS STIMULATOREN DER GUANYLATCYCLASE ZUR HERZ-KREISLAUFERKRANKUNGEN<br/>[EN] PYRAZOLOPYRIDINE, INDAZOLE, IMIDAZOPYRIDINE, IMIDAZOPYRIMIDINE, PYRAZOLOPYRAZINE AND PYRAZOLOPYRIDINE DERIVATES AS STIMULATORS OF GUANYLATE CYCLASE FOR CARDIOVASCULAR DISORDERS<br/>[FR] DÉRIVÉ DE PYRAZOLOPYRIDINE, INDAZOLE, IMIDAZOPYRIDINE, IMIDAZOPYRIMIDINE, PYRAZOLOPYRAZINE ET PYRAZOLOPYRIDINE EN TANT QUE STIMULANT DE LA GUANYLATCYCLASE POUR LES MALADIES CARDIOVASCULAIRES
  申请人：BAYER HEALTHCARE AG

  公开号：WO2008031513A1

  公开（公告）日：2008-03-20

  [EN] The present application relates to compounds of the formula (I) which act as stimulators of soluble guanylate cyclase and to their use for treatment and/or prevention of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischaemias, vascular disorders, thromboembolic disorders and arteriosclerosis. L-CH₂-M-Q (I) in which L is phenyl, pyridyl, furyl, thienyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl or (C₅-C₇)-cycloalkyl, M is a bicyclic heteroaryl group of the formula (a-1), (b-1) or (c-1), in which the attachment site to the group is -CH₂-L, the attachment site to the group is Q, and A, B, D and E are each CH, CR¹ or N, where not more than two of the ring members A, B, D and E are the same, and Q is an unsaturated or aromatic 5- or 6-membered heterocycle having up to four heteroatoms from the group of N, O and/or S.
  [FR] La présente invention concerne un composé de formule (I), qui agit en tant que stimulant de la guanylatcyclase soluble et son utilisation pour le traitement et/ou la prévention de l'insuffisance cardiaque, de l'angine de poitrine, de l'hypertonie, de l'hypertonie pulmonaire, de l'ischémie, des angiopathies, des maladies thromboemboliques et de l'artériosclérose. L-CH₂-M-Q (I) dans laquelle L représente phényle, pyridyle, furyle, thiényle, thiazolyle, oxazolyle, isothiazolyle, isoxazolyle ou un cycloalkyle en (C₅-C₇), M représente un groupement hétéroaryle de formule (a-1), (b-1) ou (c-1), le site de liaison représentant le groupement -CH₂-L, le site de liaison représentant le groupement Q, A, B, D et E représentant chacun CH, CR¹ ou N. Selon l'invention, au plus deux des éléments cycliques A, B, D et E sont identiques et Q représente un hétérocycle insaturé ou aromatique ayant 5 ou 6 éléments, avec jusqu'à quatre hétéroatomes de la série N, O et/ou S.
  [DE] Die vorliegende Anmeldung betrifft Verbindung der Formel (I), die als Simulatoren der löslichen Guanylatcyclase wirken und ihre Verwendung zur Behandlung und/oder Prävention von Herzinsuffizienz, Angina pectoris, Hypertonie, pulmonaler Hypertonie, Ischämien, Gefässerkrankungen, thromboembolischen Erkrankungen und Arteriosklerose. L-CH₂-M-Q (I) in welcher L für Phenyl, Pyridyl, Furyl, Thienyl, Thiazolyl, Oxazolyl, Isothiazolyl, Isoxazolyl oder (C₅-C₇)-Cycloalkyl, M für eine bicyclische Heteroaryl-Gruppe der Formel (a-1), (b-1) oder (c-1) steht, worin die Verknüpfungsstelle mit der Gruppe -CH₂-L bedeutet, die Verknüpfungsstelle mit der Gruppe Q bedeutet, A, B, D und E jeweils CH, CR¹ oder N bedeuten, wobei maximal zwei der Ringglieder A, B, D und E zugleich stehen, und Q für einen ungesättigten oder aromatischen 5- oder 6-gliedrigen Heterocyclus mit bis zu vier Heteroatomen aus der Reihe N1 O und/oder S steht.