1-octyl-5-phenyl-1H-imidazol-2-amine | 1261076-14-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-octyl-5-phenyl-1H-imidazol-2-amine
• 英文别名: 1-Octyl-5-phenylimidazol-2-amine
• CAS: 1261076-14-5
• 化学式: C₁₇H₂₅N₃
• 分子量: 271.406
• InChiKey: MUTKNZVISPDHQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-octyl-5-phenyl-1H-imidazol-2-amine 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以103 mg的产率得到1-octyl-5-phenyl-1H-imidazol-2-amine hydrochloride
  参考文献：
  名称：

  1,5-二取代-2-氨基咪唑的简便合成：第一代文库的抗生素活性

  摘要：

  已经开发了从容易获得的氨基酸和醛制备1，5-二取代的2-氨基咪唑的有效合成途径。合成了一个简单的类似物文库，并显示了几种化合物对多种细菌菌株（包括耐多药分离株）表现出显着的抗生素活性。

  DOI：

  10.1016/j.bmcl.2011.05.123
• 作为产物：
  描述：

  在 氰胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 1-octyl-5-phenyl-1H-imidazol-2-amine
  参考文献：
  名称：

  1,5-二取代-2-氨基咪唑的简便合成：第一代文库的抗生素活性

  摘要：

  已经开发了从容易获得的氨基酸和醛制备1，5-二取代的2-氨基咪唑的有效合成途径。合成了一个简单的类似物文库，并显示了几种化合物对多种细菌菌株（包括耐多药分离株）表现出显着的抗生素活性。

  DOI：

  10.1016/j.bmcl.2011.05.123

文献信息

• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR CONTROLLING BIOFILMS<br/>[FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS DE LUTTE CONTRE LES BIOFILMS
  申请人：UNIV LEUVEN KATH

  公开号：WO2017070755A1

  公开（公告）日：2017-05-04

  The present invention relates to substituted 5-aryl-2-aminoimidiazole compounds being active against microbial biofilm formation. The invention also relates to compositions comprising a microbial biofilm inhibiting amount of said substituted 5-aryl-2-aminoimidiazole compounds in combination with excipients. Methods for inhibiting or controlling microbial biofilm formation in a plant, a body part of a human or an animal, or a surface with which a human or an animal may come into contact are also disclosed.

  本发明涉及对微生物生物膜形成具有活性的取代5-芳基-2-氨基咪唑化合物。该发明还涉及包含所述取代5-芳基-2-氨基咪唑化合物的微生物生物膜抑制量与赋形剂结合的组合物。还公开了在植物、人类或动物的身体部位，或人类或动物可能接触的表面上抑制或控制微生物生物膜形成的方法。
• Modulation of the Substitution Pattern of 5-Aryl-2-Aminoimidazoles Allows Fine-Tuning of Their Antibiofilm Activity Spectrum and Toxicity
  作者：Elien Peeters、Geert Hooyberghs、Stijn Robijns、Kai Waldrant、Ami De Weerdt、Nicolas Delattin、Veerle Liebens、Soňa Kucharíková、Hélène Tournu、Natalie Verstraeten、Barbara Dovgan、Lenart Girandon、Mirjam Fröhlich、Katrijn De Brucker、Patrick Van Dijck、Jan Michiels、Bruno P. A. Cammue、Karin Thevissen、Jozef Vanderleyden、Erik Van der Eycken、Hans P. Steenackers

  DOI：10.1128/aac.00035-16

  日期：2016.11

  We previously synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N 1- and 2 N -substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N 1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2 N -substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N 1 and 2 N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N 1-,2 N -disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N 1-,2 N -disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N 1 and 2 N of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity.

  摘要 我们以前合成了几个基于 5-芳基-2-氨基咪唑支架的化合物系列，这些化合物显示出了防止肠炎沙门氏菌形成的活性。 肠炎沙门氏菌 血清伤寒沙门氏菌和 铜绿假单胞菌 生物膜的形成。在此，我们进一步研究了一些活性最强的 N 1- 和 2 N -取代的 5-芳基-2-氨基咪唑类化合物对单种和混合种细菌和真菌形成的多种生物膜的活性谱。对 N 1 取代的化合物对革兰氏阴性和革兰氏阳性细菌形成的生物膜以及真菌 白色念珠菌 但以前的研究表明，它对多种真核细胞系具有毒性。相比之下，2 N -取代的化合物对革兰氏阴性细菌和白念珠菌形成的生物膜无毒且具有活性。 白僵菌 但对革兰氏阳性菌形成的生物膜的活性降低。为了开发对革兰氏阳性菌形成的生物膜具有强效活性的无毒化合物，并将其应用于医疗植入物的抗生物膜涂层，我们合成了新型化合物，其取代基位于 N 1 和 2 N 位置上都有取代基的新型化合物，并测试了这些化合物的抗生物膜活性和毒性。有趣的是，这些化合物中的大多数 N 1-,2 N -二取代的 5-芳基-2-氨基咪唑对革兰氏阳性菌和白僵菌形成的生物膜具有很强的活性。 白僵菌 但对革兰氏阴性菌形成的生物膜却失去了活性。鉴于这些化合物可用作骨科植入物的抗感染涂层，我们测试了它们对两种骨细胞系的毒性以及这些细胞的功能。结果表明 N 1-,2 N -二取代的 5-芳基-2-氨基咪唑一般不会影响骨细胞的活力，甚至还会诱导钙沉积。这表明，通过改变 N N 1和2 N 位上的取代模式，可以对抗生纤活性谱和毒性进行微调。
• Structure−Activity Relationship of 4(5)-Aryl-2-amino-1<i>H</i>-imidazoles, <i>N</i>1-Substituted 2-Aminoimidazoles and Imidazo[1,2-<i>a</i>]pyrimidinium Salts as Inhibitors of Biofilm Formation by <i>Salmonella</i> Typhimurium and <i>Pseudomonas aeruginosa</i>
  作者：Hans P. L. Steenackers、Denis S. Ermolat’ev、Bharat Savaliya、Ami De Weerdt、David De Coster、Anamik Shah、Erik V. Van der Eycken、Dirk E. De Vos、Jozef Vanderleyden、Sigrid C. J. De Keersmaecker

  DOI：10.1021/jm1011148

  日期：2011.1.27

  A library of 112 4(5)-aryl-2-amino-1H-imidazoles, 4,5-diphenyl-2-amino-1H-imidazoles, and N1-substituted 4(5)-phenyl-2-aminoimidazoles was synthesized and tested for the antagonistic effect against biofilm formation by Salmonella Typhimurium and Pseudomonas aeruginosa. The substitution pattern of the 4(5)phenyl group and the nature of the N1-substituent were found to have a major effect on the biofilm inhibitory activity. The most active compounds of this series were shown to inhibit the biofilm formation at low micromolar concentrations. Furthermore, the influence of 6 imidazo[1,2-a]pyrimidines and 18 imidazo[1,2-a]pyrimidinium salts on the biofilm formation was tested. These compounds are the chemical precursors of the 2-aminoimidazoles in our synthesis pathway. A good correlation was found between the activity of the imidazo[1,2-a]pyrimidinium salts and their corresponding 2-aminoimidazoles, supporting the hypothesis that the imidazo[1,2-a]pyrimidinium salts are possibly cleaved by cellular nucleophiles to form the active 2-aminoimidazoles. However, the imidazo[1,2-a]pyrimidines did not show any biofilm inhibitory activity, indicating that these molecules are not susceptible to in situ degradation to 2-aminoimidazoles. Finally, we demonstrated the lack of biofilm inhibitory activity of an array of 37 2N-substituted 2-aminopyrimidines, which are the chemical precursors of the imidazo[1,2-a]pyrimidinium salts in our synthesis pathway.
• A facile synthesis of 1,5-disubstituted-2-aminoimidazoles: Antibiotic activity of a first generation library
  作者：Tyler L. Harris、Roberta J. Worthington、Christian Melander

  DOI：10.1016/j.bmcl.2011.05.123

  日期：2011.8

  An efficient synthetic route to 1,5-disubstituted 2-aminoimidazoles from readily available amino acids and aldehydes has been developed. A library of simple analogues was synthesized and several compounds were shown to exhibit notable antibiotic activity against a variety of bacterial strains including multi-drug resistant isolates.

  已经开发了从容易获得的氨基酸和醛制备1，5-二取代的2-氨基咪唑的有效合成途径。合成了一个简单的类似物文库，并显示了几种化合物对多种细菌菌株（包括耐多药分离株）表现出显着的抗生素活性。