1-甲基-2-吡啶-3-基-1,2,3,4-四氢萘-1-醇 | 93008-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 1-甲基-2-吡啶-3-基-1,2,3,4-四氢萘-1-醇
• 英文名称: 1-methyl-2-pyridin-3-yl-1,2,3,4-tetrahydronaphthalen-1-ol
• 英文别名: 1-methyl-2-pyridin-3-yl-1,2,3,4-tetrahydro-naphthalen-1-ol；3-<1-Hydroxy-1-methyl-1,2,3,4-tetrahydro-naphthyl-(2)>-pyridin；1-Methyl-2-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ol；1-methyl-2-pyridin-3-yl-3,4-dihydro-2H-naphthalen-1-ol
• CAS: 93008-02-7
• 化学式: C₁₆H₁₇NO
• 分子量: 239.317
• InChiKey: CKGNGPQHAZSLBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  1-甲基-2-吡啶-3-基-1,2,3,4-四氢萘-1-醇 在 盐酸 作用下， 反应 2.0h， 以63%的产率得到3-(1-甲基-3,4-二氢-2-萘)-吡啶
  参考文献：
  名称：

  Synthesis and Evaluation of Heteroaryl-Substituted Dihydronaphthalenes and Indenes:  Potent and Selective Inhibitors of Aldosterone Synthase (CYP11B2) for the Treatment of Congestive Heart Failure and Myocardial Fibrosis

  摘要：

  In this study, the synthesis and biological evaluation of heteroaryl-substituted dihydronaphthalenes and indenes (1-16) is described. The compounds were tested for activity by use of human CYP11B2 expressed in fission yeast and V79 MZh cells and for selectivity by use of human CYP11B1, CYP17, and CYP19. The most active inhibitor was the 6-methoxydihydronaphthalene 4 (IC50 = 2 nM), showing a K-i value of 1.3 nM and a competitive type of inhibition. The 5-methoxyindene 3 was found to be the most selective CYP11B2 inhibitor (IC50 = 4 nM; CYP11B1 IC50 = 5684 nM), which also showed only marginal inhibition of human CYP3A4 and CYP2D6. Docking and molecular dynamics studies using our homology-modeled CYP11B2 structure were performed to understand some structure-activity relationships. Caco-2 cell experiments revealed highly cell-permeable compounds, and metabolic studies with 4 using rat liver microsomes showed sufficient stability.

  DOI：

  10.1021/jm060055x
• 作为产物：
  描述：

  3-吡啶乙腈 在 sodium hydroxide 、 PPA 、 sodium amide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 33.33h， 生成 1-甲基-2-吡啶-3-基-1,2,3,4-四氢萘-1-醇
  参考文献：
  名称：

  Synthesis and Evaluation of Heteroaryl-Substituted Dihydronaphthalenes and Indenes:  Potent and Selective Inhibitors of Aldosterone Synthase (CYP11B2) for the Treatment of Congestive Heart Failure and Myocardial Fibrosis

  摘要：

  In this study, the synthesis and biological evaluation of heteroaryl-substituted dihydronaphthalenes and indenes (1-16) is described. The compounds were tested for activity by use of human CYP11B2 expressed in fission yeast and V79 MZh cells and for selectivity by use of human CYP11B1, CYP17, and CYP19. The most active inhibitor was the 6-methoxydihydronaphthalene 4 (IC50 = 2 nM), showing a K-i value of 1.3 nM and a competitive type of inhibition. The 5-methoxyindene 3 was found to be the most selective CYP11B2 inhibitor (IC50 = 4 nM; CYP11B1 IC50 = 5684 nM), which also showed only marginal inhibition of human CYP3A4 and CYP2D6. Docking and molecular dynamics studies using our homology-modeled CYP11B2 structure were performed to understand some structure-activity relationships. Caco-2 cell experiments revealed highly cell-permeable compounds, and metabolic studies with 4 using rat liver microsomes showed sufficient stability.

  DOI：

  10.1021/jm060055x

文献信息

• Selective Inhibitors of Human Corticosteroid Synthases
  申请人：Hartmann Rolf W.

  公开号：US20090221591A1

  公开（公告）日：2009-09-03

  The invention relates to compounds for selectively inhibiting human corticosteroid synthases CYP1 1 B1 and CYP1 1 B2, and to the production and use thereof for treating hypercortisolism, diabetes mellitus, hyperaldosteronism, cardiac insufficiency, myocardial fibrosis, depression, age-related cognitive decline and metabolic syndrome.

  本发明涉及用于选择性抑制人类皮质类固醇合成酶CYP11B1和CYP11B2的化合物，以及其生产和用于治疗高皮质醇症，糖尿病，高醛固酮症，心力衰竭，心肌纤维化，抑郁症，年龄相关认知衰退和代谢综合征。
• US9271963B2
  申请人：——

  公开号：US9271963B2

  公开（公告）日：2016-03-01
• Synthesis and Evaluation of Heteroaryl-Substituted Dihydronaphthalenes and Indenes:  Potent and Selective Inhibitors of Aldosterone Synthase (CYP11B2) for the Treatment of Congestive Heart Failure and Myocardial Fibrosis
  作者：Marieke Voets、Iris Antes、Christiane Scherer、Ursula Müller-Vieira、Klaus Biemel、Sandrine Marchais-Oberwinkler、Rolf W. Hartmann

  DOI：10.1021/jm060055x

  日期：2006.4.1

  In this study, the synthesis and biological evaluation of heteroaryl-substituted dihydronaphthalenes and indenes (1-16) is described. The compounds were tested for activity by use of human CYP11B2 expressed in fission yeast and V79 MZh cells and for selectivity by use of human CYP11B1, CYP17, and CYP19. The most active inhibitor was the 6-methoxydihydronaphthalene 4 (IC50 = 2 nM), showing a K-i value of 1.3 nM and a competitive type of inhibition. The 5-methoxyindene 3 was found to be the most selective CYP11B2 inhibitor (IC50 = 4 nM; CYP11B1 IC50 = 5684 nM), which also showed only marginal inhibition of human CYP3A4 and CYP2D6. Docking and molecular dynamics studies using our homology-modeled CYP11B2 structure were performed to understand some structure-activity relationships. Caco-2 cell experiments revealed highly cell-permeable compounds, and metabolic studies with 4 using rat liver microsomes showed sufficient stability.