methyl 3-chloro-4-[(2-chloroacetyl)amido]benzoate

• 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: methyl 3-chloro-4-[(2-chloroacetyl)amido]benzoate
• 英文别名: Methyl 3-chloro-4-[(2-chloroacetyl)amino]benzoate；methyl 3-chloro-4-[(2-chloroacetyl)amino]benzoate
• 化学式: C₁₀H₉Cl₂NO₃
• 分子量: 262.092
• InChiKey: KYRSICOSUYFIDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-chloro-4-[(2-chloroacetyl)amido]benzoate 、 1-(3,5-dimethylphenylsulfonyl)-1,3-dihydro-2H-benzimidazole-2-thione 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以56%的产率得到methyl-3-chloro-4-{[({1-[(3,5-dimethylphenyl)sulfonyl]-1H-benzimidazol-2-yl}sulfanyl)acetyl]amino}benzoate
  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：

  甲基4-氨基-3-氯化苯甲酸盐 、 氯乙酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以75%的产率得到methyl 3-chloro-4-[(2-chloroacetyl)amido]benzoate
  参考文献：
  名称：

  N 1-芳基-苯并咪唑类化合物的结构优化，用于发现对野生型和突变型HIV-1菌株具有活性的新型非核苷类逆转录酶抑制剂

  摘要：

  非核苷逆转录酶抑制剂（NNRTIs）是推荐的抗逆转录病毒联合疗法的成分，可用于治疗人类免疫缺陷病毒（HIV）感染。这些方案在抑制病毒复制方面极为有效。最近，我们的研究小组确定了一些N 1-芳基-2-芳基硫代乙酰氨基-苯并咪唑类作为一类新的NNRTIs。在这项研究工作中，我们报告了新化合物的设计，合成以及结构与活性之间的关系（20 – 34），其中已引入一些结构修饰，以研究其对逆转录酶（RT）抑制的影响并更好地定义增加抗病毒活性所需的功能。事实证明，大多数新化合物都能以最小的细胞毒性抑制纳摩尔浓度的RT酶和MT4细胞中HIV-1的复制。其中，最有前途的N 1-芳基-2-芳硫基乙酰乙酰氨基-苯并咪唑和N 1-芳基-2-芳氧基乙酰胺基-苯并咪唑也针对一组对NNRTIs具有抗性的单突变体和双突变体菌株进行了测试，显示了体外对单个突变体L100I，K103N，Y181C，Y188L和E138K的抗病

  DOI：

  10.1016/j.bmc.2017.12.033

文献信息

• Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: Optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches
  作者：Boshi Huang、Cuicui Li、Wenmin Chen、Tao Liu、Mingyan Yu、Lu Fu、Yueyue Sun、Huiqing Liu、Erik De Clercq、Christophe Pannecouque、Jan Balzarini、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2015.01.042

  日期：2015.3

  In our arduous efforts to develop new potent HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs), novel piperidine-linked [1,2,4]triazolo[1,5-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiviral activities in MT-4 cell cultures. Biological results showed that all of the title compounds displayed moderate to excellent activities against wild-type (wt)

  在我们努力开发新的有效HIV-1非核苷逆转录酶（RT）抑制剂（NNRTIs）的过程中，设计，合成和合成了新的哌啶连接的[1,2,4]三唑并[1,5- a ]嘧啶衍生物。评估其在MT-4细胞培养物中的抗病毒活性。生物学结果表明，在基于细胞的测定中，所有标题化合物均显示出对野生型（wt）HIV-1菌株（III B）的中等至优异的活性，EC 50值为8.1 nM至2284 nM。其中，最有前途的类似物7d对野生型HIV-1的EC 50值为8.1 nM，比参考药物DDI，3 TC，NVP和DLV更有力。此外，7天证明对双重突变HIV-1菌株（K103N + Y181C）的活性较弱，并且在RT抑制试验中比NVP更有效。此外，还详细讨论了7d的一些测量和计算的理化性质，例如log P和水溶性，以及结构-活性关系（SARs）分析。此外，通过分子模拟研究使活性化合物7d的结合模式合理化。
• 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.
• Tri-substituted triazoles as potent non-nucleoside inhibitors of the HIV-1 reverse transcriptase
  作者：Martha De La Rosa、Hong Woo Kim、Esmir Gunic、Cheryl Jenket、Uyen Boyle、Yung-hyo Koh、Ilia Korboukh、Matthew Allan、Weijian Zhang、Huanming Chen、Wen Xu、Shahul Nilar、Nanhua Yao、Robert Hamatake、Stanley A. Lang、Zhi Hong、Zhijun Zhang、Jean-Luc Girardet

  DOI：10.1016/j.bmcl.2006.06.048

  日期：2006.9

  A new series of 1,2,4-triazoles was synthesized and tested against several NNRTI-resistant HIV-1 isolates. Several of these compounds exhibited potent antiviral activities against efavirenz- and nevirapine-resistant viruses, containing K103N and/or Y181C mutations or Y188L mutation. Triazoles were first synthesized from commercially available substituted phenylthio-semicarbazides, then from isothiocyanates, and later by condensing the desired substituted anilines with thiosemicarbazones. (c) 2006 Elsevier Ltd. All rights reserved.
• Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors
  作者：Xiao Li、Xueyi Lu、Wenmin Chen、Huiqing Liu、Peng Zhan、Christophe Pannecouque、Jan Balzarini、Erik De Clercq、Xinyong Liu

  DOI：10.1016/j.bmc.2014.08.001

  日期：2014.10

  A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations.