6-chloro-1-(3,5-dimethylbenzyl)-1,3-dihydro-2H-benzimidazole-2-thione | 1061732-18-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 6-chloro-1-(3,5-dimethylbenzyl)-1,3-dihydro-2H-benzimidazole-2-thione
• 英文别名: 5-chloro-3-[(3,5-dimethylphenyl)methyl]-1H-benzimidazole-2-thione
• CAS: 1061732-18-0
• 化学式: C₁₆H₁₅ClN₂S
• 分子量: 302.827
• InChiKey: XSPCPGMXRMWJOO-UHFFFAOYSA-N

物化性质

• 熔点：
  263-265 °C(Solvent: Ethanol)
• 沸点：
  461.0±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  47.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-chloro-1-(3,5-dimethylbenzyl)-1,3-dihydro-2H-benzimidazole-2-thione 、 N-(2-溴-苯基)-2-氯-乙酰胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以92%的产率得到2-{[6-chloro-1-(3,5-dimethylbenzyl)-1H-benzimidazol-2-yl]sulfanyl}-N-2-bromophenylacetamide
  参考文献：
  名称：

  Design and synthesis of N1-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors

  摘要：

  A series of novel N-1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.045
• 作为产物：
  描述：

  3,5-二甲基溴苄 在 盐酸 、 sodium hydride 、 锌 作用下， 以 吡啶 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 6-chloro-1-(3,5-dimethylbenzyl)-1,3-dihydro-2H-benzimidazole-2-thione
  参考文献：
  名称：

  Design and synthesis of N1-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors

  摘要：

  A series of novel N-1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.045

文献信息

• Novel N1-substituted 1,3-dihydro-2H-benzimidazol-2-ones as potent non-nucleoside reverse transcriptase inhibitors
  作者：Anna-Maria Monforte、Angela Rao、Patrizia Logoteta、Stefania Ferro、Laura De Luca、Maria Letizia Barreca、Nunzio Iraci、Giovanni Maga、Erik De Clercq、Christophe Pannecouque、Alba Chimirri

  DOI：10.1016/j.bmc.2008.06.012

  日期：2008.8

  synthesized and evaluated as anti-HIV agents. Some of them proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentration as potent non-nucleoside HIV-1 RT inhibitors (NNRTIs) with low cytotoxicity. SAR studies highlighted that the nature of the substituents at N(1) and on the benzene ring of benzimidazolone moiety significantly influenced the anti-HIV activity of this class

  合成了多个N（1）-取代的1,3-二氢-2H-苯并咪唑-2-酮，并作为抗HIV药物进行了评估。它们中的一些被证明在纳摩尔浓度下作为抑制细胞毒性低的有效非核苷HIV-1 RT抑制剂（NNRTIs）能有效抑制HIV-1复制。SAR研究突出表明，苯并咪唑酮部分的N（1）和苯环上的取代基的性质显着影响此类有效的抗逆转录病毒药物的抗HIV活性。
• Design and synthesis of N1-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors
  作者：Anna-Maria Monforte、Stefania Ferro、Laura De Luca、Giuseppa Lo Surdo、Francesca Morreale、Christophe Pannecouque、Jan Balzarini、Alba Chimirri

  DOI：10.1016/j.bmc.2013.12.045

  日期：2014.2

  A series of novel N-1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies. (C) 2014 Elsevier Ltd. All rights reserved.
• Discovery of benzimidazole-based<i>Leishmania mexicana</i>cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis
  作者：Laura De Luca、Stefania Ferro、Maria Rosa Buemi、Anna-Maria Monforte、Rosaria Gitto、Tanja Schirmeister、Louis Maes、Antonio Rescifina、Nicola Micale

  DOI：10.1111/cbdd.13326

  日期：2018.9

  Chemotherapy is currently the only effective approach to treat all forms of leishmaniasis. However, its effectiveness is severely limited due to high toxicity, long treatment length, drug resistance, or inadequate mode of administration. As a consequence, there is a need to identify new molecular scaffolds and targets as potential therapeutics for the treatment of this disease. We report a small series of 1,2‐substituted‐1H‐benzo[d]imidazole derivatives (9a–d) showing affinity in the submicromolar range (Ki = 0.15–0.69 μM) toward Leishmania mexicanaCPB2.8ΔCTE, one of the more promising targets for antileishmanial drug design. The compounds confirmed activity in vitro against intracellular amastigotes of Leishmania infantum with the best result being obtained with derivative 9d (IC50 = 6.8 μM), although with some degree of cytotoxicity (CC50 = 8.0 μM on PMM and CC50 = 32.0 μM on MCR‐5). In silico molecular docking studies and ADME‐Tox properties prediction were performed to validate the hypothesis of the interaction with the intended target and to assess the drug‐likeness of these derivatives.