(R)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol | 368884-18-8

• 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: (R)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol
• 英文别名: 1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol；(R)-1-(4-Fluoro-phenyl)-2-Imidazol-1-yl-ethanol；(1R)-1-(4-fluorophenyl)-2-imidazol-1-ylethanol
• CAS: 368884-18-8
• 化学式: C₁₁H₁₁FN₂O
• 分子量: 206.22
• InChiKey: NRDFBOYEUSTTCC-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanol 在 三乙胺 作用下， 以 乙醚 、 乙腈 为溶剂， 生成 (R)-1-(4-fluorophenyl)-2-(1H-imidazol-1-yl)ethyl 3-(1H-imidazolyl)propylcarbamate
  参考文献：
  名称：

  Structural Basis for Rational Design of Inhibitors Targeting Trypanosoma cruzi Sterol 14α-Demethylase: Two Regions of the Enzyme Molecule Potentiate Its Inhibition

  摘要：

  Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global, becoming a new worldwide challenge with no cure available. The disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14 alpha-demethylase (CYP51) inhibitors. Here we explore the spectral binding parameters, inhibitory effects on T. cruzi CYP51 activity, and antiparasitic potencies of a new set of beta-phenyl imidazoles. Comparative structural characterization of the T. cruzi CYP51 complexes with the three most potent inhibitors reveals two opposite binding modes of the compounds ((R)-6, EC50 = 1.2 nM, vs (S)-2/(S)-3, EC50 = 1.0/5.5 nM) and suggests the entrance into the CYP51 substrate access channel and the heme propionate-supporting ceiling of the binding cavity as two distinct areas of the protein that enhance molecular recognition and therefore could be used for the development of more effective antiparasitic drugs.

  DOI：

  10.1021/jm500739f
• 作为产物：
  描述：

  1-(4-氟苯基)-2-(1H-咪唑-1-基)-乙酮 在 nicotinamide adenine dinucleotide phosphate 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 以99%的产率得到
  参考文献：
  名称：

  基于酮还原酶不对称合成 β-杂芳基氨基醇的三步化学酶级联合成咪康唑类似物

  摘要：

  手性 β-杂芳基氨基醇作为中间体在许多生物活性药物的合成中发挥着至关重要的作用，包括西诺贝酯、奥替康唑和咪康唑。然而，缺乏文献记录建立合成β-杂芳基氨基醇和上述药物的通用方法。在这项研究中，我们使用两种具有相反立体选择性的工程酮还原酶（KRED）成功不对称合成了 50 对手性 β-杂芳基氨基醇。基于这一成果，我们开发了一种三步化学酶级联路线，用于从市售的 2-溴苯乙酮衍生物合成手性咪康唑类似物。通过优化第一步合成α-咪唑基酮的溶剂，然后在第二步中使用KREDs还原α-咪唑基酮，并在第三步中进行醚化，我们获得了20种具有良好产率的手性咪康唑类似物（26 –84%）和令人印象深刻的立体选择性（高达 >99% ee）。值得注意的是，该路线无需分离酮和醇中间体，并避免在手性咪康唑类似物的合成中使用金属催化剂。此外，我们成功放大了( S )-咪康唑的制备，实现了30%的分离收率和>99% ee。该方

  DOI：

  10.1002/adsc.202300740

文献信息

• 5- substituted tetralones as inhibitors of ras farnesyl trransferase
  申请人：——

  公开号：US20040044057A1

  公开（公告）日：2004-03-04

  The present invention provides novel 5-substituted tetralones of Formulas (I), (II), (III) and (IV) and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof, which are useful for treating and preventing uncontrolled or abnormal proliferation of tissues, such as cancer, atherosclerosis, restenosis, and psoriasis. Specifically, the present invention relates to compounds that inhibit the farnesyl transferase enzyme. 1

  本发明提供了式(I)、(II)、(III)和(IV)的新型5-取代四酮及其药学上可接受的盐、酯、酰胺和前药，用于治疗和预防组织的不受控制或异常增殖，如癌症、动脉粥样硬化、再狭窄和银屑病。具体而言，本发明涉及抑制法尼基转移酶酶的化合物。
• In vitro screening of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives as antiprotozoal agents and docking studies on Trypanosoma cruzi CYP51
  作者：Daniela De Vita、Francesca Moraca、Claudio Zamperini、Fabiana Pandolfi、Roberto Di Santo、An Matheeussen、Louis Maes、Silvano Tortorella、Luigi Scipione

  DOI：10.1016/j.ejmech.2016.02.028

  日期：2016.5

  of many parasite protozoa, such as Trypanosoma and Leishmania species, thus representing a valuable drug target for the treatment of Kinetoplastid diseases. A set of azole-based compounds selected from an in-house compound library was in vitro screened against different human protozoan parasites. Several compounds showed selective activity against Trypanosoma cruzi, with compound 7 being the most active

  甾醇14α-脱甲基酶（CYP51）是一种参与许多寄生虫原生动物（如锥虫和利什曼原虫）的存活和致病性的关键酶，因此代表了治疗运动质体疾病的重要药物靶标。从内部化合物库中选出的一组基于唑的化合物在体外针对不同的人类原生动物寄生虫进行了筛选。几种化合物显示出对克氏锥虫的选择性活性，其中化合物7的活性最高（IC 50 = 40 nM）。考虑到此处报道的化合物与已知的CYP51抑制剂之间的结构相似性，进行了分子对接研究，以评估其与原生动物靶标的结合并合理化生物学活性数据。
• Miconazole-like Scaffold is a Promising Lead for <i>Naegleria fowleri</i>-Specific CYP51 Inhibitors
  作者：Vandna Sharma、Valentina Noemi Madia、Valeria Tudino、Jennifer V. Nguyen、Anjan Debnath、Antonella Messore、Davide Ialongo、Elisa Patacchini、Irene Palenca、Silvia Basili Franzin、Luisa Seguella、Giuseppe Esposito、Rita Petrucci、Paola Di Matteo、Martina Bortolami、Francesco Saccoliti、Roberto Di Santo、Luigi Scipione、Roberta Costi、Larissa M. Podust

  DOI：10.1021/acs.jmedchem.3c01898

  日期：2023.12.28
• US6943183B2
  申请人：——

  公开号：US6943183B2

  公开（公告）日：2005-09-13
• Structural Basis for Rational Design of Inhibitors Targeting <i>Trypanosoma cruzi</i> Sterol 14α-Demethylase: Two Regions of the Enzyme Molecule Potentiate Its Inhibition
  作者：Laura Friggeri、Tatiana Y. Hargrove、Girish Rachakonda、Amanda D. Williams、Zdzislaw Wawrzak、Roberto Di Santo、Daniela De Vita、Michael R. Waterman、Silvano Tortorella、Fernando Villalta、Galina I. Lepesheva

  DOI：10.1021/jm500739f

  日期：2014.8.14

  Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global, becoming a new worldwide challenge with no cure available. The disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14 alpha-demethylase (CYP51) inhibitors. Here we explore the spectral binding parameters, inhibitory effects on T. cruzi CYP51 activity, and antiparasitic potencies of a new set of beta-phenyl imidazoles. Comparative structural characterization of the T. cruzi CYP51 complexes with the three most potent inhibitors reveals two opposite binding modes of the compounds ((R)-6, EC50 = 1.2 nM, vs (S)-2/(S)-3, EC50 = 1.0/5.5 nM) and suggests the entrance into the CYP51 substrate access channel and the heme propionate-supporting ceiling of the binding cavity as two distinct areas of the protein that enhance molecular recognition and therefore could be used for the development of more effective antiparasitic drugs.