(1-methyl-1H-imidazol-5-yl)-(4-methylphenyl)methanone | 1227383-30-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1-methyl-1H-imidazol-5-yl)-(4-methylphenyl)methanone
• 英文别名: (3-methyl-3H-imidazol-4-yl)-p-tolylmethanone；1-Methyl-5-(4-methylbenzoyl)-1H-imidazole；(3-methylimidazol-4-yl)-(4-methylphenyl)methanone
• CAS: 1227383-30-3
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: IVCGFEYUIUNJNE-UHFFFAOYSA-N

物化性质

• 沸点：
  412.1±20.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  p-tolyl-(1-trityl-1H-imidazol-4-yl)methanone 、 三氟甲烷磺酸甲酯 以 二氯甲烷 为溶剂， 以89.6%的产率得到(1-methyl-1H-imidazol-5-yl)-(4-methylphenyl)methanone
  参考文献：
  名称：

  Second Generation Analogues of the Cancer Drug Clinical Candidate Tipifarnib for Anti-Chagas Disease Drug Discovery

  摘要：

  We previously reported that the cancer drug clinical candidate tipifarnib kills the causative agent of Chagas disease, Trypanosoma cruzi, by blocking ergosterol biosynthesis at the level of inhibition of lanosterol 14 alpha-demethylase. Tipifarnib is an inhibitor of human protein farnesyltransferase. We synthesized tipifarnib analogues that no longer bind to protein farnesyltransferase and display increased potency for killing parasites. This was achieved in a structure-guided fashion by changing the substituents attached to the phenyl group at the 4-position of the quinoline ring of tipifarnib and by replacing the amino group by OMe. Several compounds that kill Trypanosoma cruzi at subnanomolar concentrations and are devoid of protein farnesyltransferase inhibition were discovered. The compounds are shown to be advantageous over other lanosterol 14 alpha-demethylase inhibitors in that they show only modest potency for inhibition of human cytochrome P450 (3A4). Since tipifarnib displays high oral bioavailability and acceptable pharmacokinetic properties, the newly discovered tipifarnib analogues are ideal leads for the development of drugs to treat Chagas disease.

  DOI：

  10.1021/jm9013136

文献信息

• [EN] IMIDAZOLYLKETONE DERIVATIVES ASD ALDOSTERONE SYNTHASE INHIBITORS<br/>[FR] DÉRIVÉS D'IMIDAZOLYLCÉTONE EN TANT QU'INHIBITEURS DE L'ALDOSTÉRONE SYNTHASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013120771A1

  公开（公告）日：2013-08-22

  The invention provides novel compounds having the general formula (I), wherein R1, R2, R3 and R4 n are as described herein, compositions including the compounds and methods of using the compounds as inhibitors of aldosterone synthase.

  这项发明提供了具有一般式(I)的新化合物，其中R1、R2、R3和R4 n如本文所述，包括这些化合物的组合物以及将这些化合物用作醛固酮合成酶抑制剂的方法。
• NEW IMIDAZOLYLKETONE DERIVATIVES
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20140128429A1

  公开（公告）日：2014-05-08

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 and R 4 n are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般式（I）的新化合物，其中R1、R2、R3和R4n如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• IMIDAZOLYLKETONE DERIVATIVES ASD ALDOSTERONE SYNTHASE INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2814814B1

  公开（公告）日：2019-05-08
• US9464058B2
  申请人：——

  公开号：US9464058B2

  公开（公告）日：2016-10-11
• Second Generation Analogues of the Cancer Drug Clinical Candidate Tipifarnib for Anti-Chagas Disease Drug Discovery
  作者：James M. Kraus、Hari Babu Tatipaka、Sarah A. McGuffin、Naveen Kumar Chennamaneni、Mandana Karimi、Jenifer Arif、Christophe L. M. J. Verlinde、Frederick S. Buckner、Michael H. Gelb

  DOI：10.1021/jm9013136

  日期：2010.5.27

  We previously reported that the cancer drug clinical candidate tipifarnib kills the causative agent of Chagas disease, Trypanosoma cruzi, by blocking ergosterol biosynthesis at the level of inhibition of lanosterol 14 alpha-demethylase. Tipifarnib is an inhibitor of human protein farnesyltransferase. We synthesized tipifarnib analogues that no longer bind to protein farnesyltransferase and display increased potency for killing parasites. This was achieved in a structure-guided fashion by changing the substituents attached to the phenyl group at the 4-position of the quinoline ring of tipifarnib and by replacing the amino group by OMe. Several compounds that kill Trypanosoma cruzi at subnanomolar concentrations and are devoid of protein farnesyltransferase inhibition were discovered. The compounds are shown to be advantageous over other lanosterol 14 alpha-demethylase inhibitors in that they show only modest potency for inhibition of human cytochrome P450 (3A4). Since tipifarnib displays high oral bioavailability and acceptable pharmacokinetic properties, the newly discovered tipifarnib analogues are ideal leads for the development of drugs to treat Chagas disease.