1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazole-5-carbaldehyde | 312936-81-5

• 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'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazole-5-carbaldehyde
• 英文别名: 3-[[4-[4-(Trifluoromethyl)phenyl]phenyl]methyl]imidazole-4-carbaldehyde
• CAS: 312936-81-5
• 化学式: C₁₈H₁₃F₃N₂O
• 分子量: 330.309
• InChiKey: QTHUMWHPPXBJRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazole-5-carbaldehyde 在 硅酸四乙酯 、 palladium 10% on activated carbon 、 二苯基膦叠氮化物 、 氢气 、 三乙酰氧基硼氢化钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 44.0h， 生成 1-((5-(((2-(diethylamino)ethyl)(methyl)amino)methyl)-1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazol-2-yl)methyl)-2-thioxo-2,3,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-4(5H)-one
  参考文献：
  名称：

  Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA2 inhibitors

  摘要：

  This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA(2) inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.062
• 作为产物：
  描述：

  4-溴苯胺 在 盐酸 、 manganese(IV) oxide 、 四(三苯基膦)钯 、 双氧水 、 caesium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 17.38h， 生成 1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazole-5-carbaldehyde
  参考文献：
  名称：

  Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA2 inhibitors

  摘要：

  This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA(2) inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.062

文献信息

• AZOLE HETEROCYCLIC COMPOUND, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP2725024A1

  公开（公告）日：2014-04-30

  The present invention relates to the filed of pharmarcutical chemistry, and in particular, to a novel class of azole compounds represented by general formula (I), (II) or (III) amd a preparation method thereof, a pharmarcutical composition with the compounds as active components, and a use of the azole compounds and the pharmarcutical composition in the preparation of a medicament for treatment of diseases associated with Lp-PLA2 enzyme activities, wherein each substituent is as deinfed in the specifictaion.

  本发明涉及药物化学领域，特别是一种由一般式（I）、（II）或（III）表示的新型类唑化合物，以及其制备方法，以这些化合物为活性成分的药物组合物，以及在制备用于治疗与Lp-PLA2酶活性相关疾病的药物中使用这些唑化合物和药物组合物的用途，其中每个取代基如规范中所定义。
• [EN] AZOLE HETEROCYLIC COMPOUNDS, PREPARATION METHODS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES AZOLES, PROCÉDÉS DE PRÉPARATION, COMPOSITIONS PHARMACEUTIQUES ET LEURS UTILISATIONS
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2013000108A1

  公开（公告）日：2013-01-03

  提供了式（I）或者式（II）的唑类杂环化合物、其制备方法、药物组合物及其在制备治疗与Lp-PLA2酶相关的疾病的药物中的用途，其中各取代基定义如说明书中所述。
• [EN] AZOLE HETEROCYCLIC COMPOUND, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE AZOLE, PROCÉDÉ DE PRÉPARATION, COMPOSITION PHARMACEUTIQUE ET UTILISATION
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2013000267A1

  公开（公告）日：2013-01-03

  本发明涉及药物化学领域，尤其涉及一类新颖的通式（I），（II）或（III）所示的唑类化合物及其自备方法，以该类化合物为活性成分的药物组合物，以及它们在制备治疗与Lp-PLA2酶活性有关疾病的药物中的应用。其中，各取代基的定义如说明书中所述。
• Potent inhibitors of farnesyltransferase and geranylgeranyltransferase-I
  作者：Diem N. Nguyen、Craig A. Stump、Eileen S. Walsh、Christine Fernandes、Joseph P. Davide、Michelle Ellis-Hutchings、Ronald G. Robinson、Theresa M. Williams、Robert B. Lobell、Hans E. Huber、Carolyn A. Buser

  DOI：10.1016/s0960-894x(02)00154-3

  日期：2002.5

  Compound 1 has been shown to be a dual prenylation inhibitor with FPTase (IC50 = 2 nM) and GGPTase-1 (IC50 = 95 nM). Analogues of 1, which replaced the cyanophenyl group with various biaryls, led to the discovery of highly potent dual FPTase/GGPTase-1 inhibitors. 4-Trifluoromethylphenyl, trifluoropentynyl, and trifluoropentyl were identified as good p-cyano replacements. (C) 2002 Published by Elsevier Science Ltd.
• Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA2 inhibitors
  作者：Kai Wang、Wenwei Xu、Wei Zhang、Mingguang Mo、Yiping Wang、Jianhua Shen

  DOI：10.1016/j.bmcl.2013.03.062

  日期：2013.5

  This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA(2) inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.