1-(4-cyanobenzyl)-5-bromo-1H-imidazole | 1185760-53-5

• 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: 1-(4-cyanobenzyl)-5-bromo-1H-imidazole
• 英文别名: 4-[(5-Bromo-1H-imidazol-1-yl)methyl]benzonitrile；4-[(5-bromoimidazol-1-yl)methyl]benzonitrile
• CAS: 1185760-53-5
• 化学式: C₁₁H₈BrN₃
• 分子量: 262.109
• InChiKey: MHDGKGCOBILXLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-cyanobenzyl)-5-bromo-1H-imidazole 、 3-氟苯基硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 18.0h， 以61%的产率得到1-(4-cyanobenzyl)-5-(3-fluorophenyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of 1-Benzyl-1H-imidazoles as Selective Inhibitors of Aldosterone Synthase (CYP11B2)

  摘要：

  Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, flits is achieved with mineralocorticoid receptor antagonists, however, aldosterone synthase (CYP11B2) inhibitors may offer a promising alternative. In this study, WC used three-dimensional modeling of CYP11B2 to model the binding modes of the natural substrate 18-hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead MOERAS115 (4-((5-phenyl-1H-imidazol-1-y1)methyl)benzonitrile) displaying an IC50 for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC50 for CYP11B2 6.0 nM. Selectivity 19.8). Molecular docking of the Inhibitors in the models enabled us to generate posthoc hypotheses oil their binding modes, providing a Valuable basis for future Studies and further design of CYP11B2 inhibitors.

  DOI：

  10.1021/jm901356d
• 作为产物：
  描述：

  在 水 、 溶剂黄146 、 盐酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.17h， 以84 mg的产率得到1-(4-cyanobenzyl)-5-bromo-1H-imidazole
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of 1-Benzyl-1H-imidazoles as Selective Inhibitors of Aldosterone Synthase (CYP11B2)

  摘要：

  Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, flits is achieved with mineralocorticoid receptor antagonists, however, aldosterone synthase (CYP11B2) inhibitors may offer a promising alternative. In this study, WC used three-dimensional modeling of CYP11B2 to model the binding modes of the natural substrate 18-hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead MOERAS115 (4-((5-phenyl-1H-imidazol-1-y1)methyl)benzonitrile) displaying an IC50 for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC50 for CYP11B2 6.0 nM. Selectivity 19.8). Molecular docking of the Inhibitors in the models enabled us to generate posthoc hypotheses oil their binding modes, providing a Valuable basis for future Studies and further design of CYP11B2 inhibitors.

  DOI：

  10.1021/jm901356d

文献信息

• N-benzyl imidazole derivatives and their use as aldosterone synthase inhibitors
  申请人：Maastricht University

  公开号：EP2095819A1

  公开（公告）日：2009-09-02

  The invention relates to the use of a N-benzyl 5-substituted imidazole derivative having the general formula I wherein R is (C1-3)alkyl, (C1-3)alkyloxy, halogen, nitro or cyano; R1 is (C1-6)alkyl, optionally substituted with OH, (C1-3)alkyloxy, (C1-3)alkylcarbonyloxy, (C1-3)alkyloxycarbonyl or halogen, or (C1-3)alkyloxycarbonyl; or R1 is phenyl, optionally substituted with 1-3 substituents independently selected from (C1-3)alkyl, (C1-3)alkyloxy, hydroxylmethyl and halogen; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a disorder or disease in a subject mediated by aldosterone synthase or responsive to inhibition of aldosterone synthase.

  该发明涉及使用具有通式I的N-苄基5-取代咪唑衍生物，其中R为(C1-3)烷基，(C1-3)烷氧基，卤素，硝基或氰基；R1为(C1-6)烷基，可选择地取代为羟基，(C1-3)烷氧基，(C1-3)烷基羰氧基，(C1-3)烷氧羰基或卤素，或(C1-3)烷氧羰基；或R1为苯基，可选择地取代为1-3个独立选择自(C1-3)烷基，(C1-3)烷氧基，羟甲基和卤素的取代基；或其药学上可接受的盐，用于制备一种药物，用于治疗由醛固酮合酶介导或对醛固酮合酶抑制响应的受体引起的主体的紊乱或疾病。
• [EN] N-BENZYL IMIDAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE N-BENZYL-IMIDAZOLE
  申请人：MAASTRICHT UNIVERSITY

  公开号：WO2009106640A2

  公开（公告）日：2009-09-03

  The invention relates to the use of a N-benzyl 5-substituted imidazole derivative having the general formula (I) wherein R is (C1-3)alkyl, (C1-3)alkyloxy, halogen, nitro or cyano; R1 is formyl, (C1-6)alkyl, optionally substituted with OH, (C1-3)alkyloxy, (C1-3)alkylcarbonyloxy, (C1-3)alkyloxy- carbonyl or halogen, or (C1-3)alkyloxycarbonyl; or R1 is phenyl, optionally substituted with 1 -3 substituents independently selected from (C1-3)alkyl, (C1-3)alkyloxy, hydroxylmethyl and halogen; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a disorder or disease in a subject mediated by aldosterone synthase or responsive to inhibition of aldosterone synthase.
• Synthesis, Biological Evaluation, and Molecular Modeling of 1-Benzyl-1<i>H</i>-imidazoles as Selective Inhibitors of Aldosterone Synthase (CYP11B2)
  作者：Luc Roumen、Joris W. Peeters、Judith M. A. Emmen、Ilona P. E. Beugels、Erica M. G. Custers、Marcel de Gooyer、Ralf Plate、Koen Pieterse、Peter A. J. Hilbers、Jos F. M. Smits、Jef A. J. Vekemans、Dirk Leysen、Harry C. J. Ottenheijm、Henk M. Janssen、J. J. Rob Hermans

  DOI：10.1021/jm901356d

  日期：2010.2.25

  Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, flits is achieved with mineralocorticoid receptor antagonists, however, aldosterone synthase (CYP11B2) inhibitors may offer a promising alternative. In this study, WC used three-dimensional modeling of CYP11B2 to model the binding modes of the natural substrate 18-hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead MOERAS115 (4-((5-phenyl-1H-imidazol-1-y1)methyl)benzonitrile) displaying an IC50 for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC50 for CYP11B2 6.0 nM. Selectivity 19.8). Molecular docking of the Inhibitors in the models enabled us to generate posthoc hypotheses oil their binding modes, providing a Valuable basis for future Studies and further design of CYP11B2 inhibitors.