methyl 3-(1-benzyl-1H-imidazol-5-yl)propanoate | 123261-02-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 3-(1-benzyl-1H-imidazol-5-yl)propanoate
• 英文别名: 1-benzyl-5-imidazole propionic acid methyl ester；Methyl 3-(1-Benzyl-1H-imidazol-5-yl)-propanoate；methyl 3-(3-benzylimidazol-4-yl)propanoate
• CAS: 123261-02-9
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: FEWHBUJYQHXFMV-UHFFFAOYSA-N

物化性质

• 沸点：
  405.3±25.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(1-benzyl-1H-imidazol-5-yl)propanoate 在 lithium aluminium tetrahydride 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以57%的产率得到3-(1-苄基-1H-咪唑-5-基)-1-丙醇
  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 甲醇 作用下， 反应 0.5h， 以1.18 g的产率得到methyl 3-(1-benzyl-1H-imidazol-5-yl)propanoate
  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

• Aromatase inhibiting 4(5)-imidazoles
  申请人：Farmos-Yhtyma Oy

  公开号：US05098923A1

  公开（公告）日：1992-03-24

  Imidazole derivatives of the formula: ##STR1## wherein R.sub.1, R.sub.2, R'.sub.1 and R'.sub.2 which can be the same or different, are H, CH.sub.3, C.sub.2 H.sub.5, OCH.sub.3, OH, CH.sub.2 OH, NH.sub.2 or halogen; R' if H or ##STR2## where R.sub.3 is H, CH.sub.3, or halogen; R.sub.4 is H and R.sub.5 is H or OH and R.sub.6 is H or OH or one of R.sub.5 and R.sub.6 is H and the other, together with R.sub.4, forms a bond and X and Y, which can be the same or different, are a bond, a straight C.sub.1-2 -alkyl or the corresponding alkenyl, and pharmaceutically acceptable salts thereof exhibit valuable pharmacological properties, especially aromatase inhibiting effects and are useful in the treatment of estrogen dependent diseases, e.g. breast cancer. Anti-mycotic and antifungal properties have also been found.

  咪唑衍生物的化学式为：##STR1## 其中R.sub.1、R.sub.2、R'.sub.1和R'.sub.2可以相同也可以不同，分别为H、CH.sub.3、C.sub.2 H.sub.5、OCH.sub.3、OH、CH.sub.2 OH、NH.sub.2或卤素；R'如果是H或##STR2##其中R.sub.3为H、CH.sub.3或卤素；R.sub.4为H、R.sub.5为H或OH，R.sub.6为H或OH，或者R.sub.5和R.sub.6中的一个是H，另一个与R.sub.4一起形成键，X和Y可以相同也可以不同，为键、直链C.sub.1-2-烷基或相应的烯基，及其药用盐表现出有价值的药理特性，尤其是芳香化酶抑制作用，并且在治疗依赖雌激素的疾病，如乳腺癌方面有用。还发现了抗真菌和抗霉菌特性。
• KARJALAINEN, ARTO JOHANNES;KANGES, LAURA VEIKKO MATTI;KURKELA, KAUKO OIVA+
  作者：KARJALAINEN, ARTO JOHANNES、KANGES, LAURA VEIKKO MATTI、KURKELA, KAUKO OIVA+

  DOI：——

  日期：——
• US5098923A
  申请人：——

  公开号：US5098923A

  公开（公告）日：1992-03-24
• 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.