methyl 4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carboxylate | 897774-23-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡咯类
• 英文名称: methyl 4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carboxylate
• 英文别名: methyl 4-[(4-chlorophenyl)methyl]thieno[3,2-b]pyrrole-5-carboxylate
• CAS: 897774-23-1
• 化学式: C₁₅H₁₂ClNO₂S
• mdl: MFCD15096640
• 分子量: 305.785
• InChiKey: VWMUUTXGJXBETC-UHFFFAOYSA-N

物化性质

• 沸点：
  467.8±40.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(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：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 65.0h， 生成 (R)-1-(4-(4-fluorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl)-N-(1-phenylethyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis

  摘要：

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.

  DOI：

  10.1021/jm300214e
• 作为产物：
  描述：

  4H-噻唑[3,2-B]吡咯-5-甲酸 在 potassium carbonate 、 potassium hydrogencarbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 methyl 4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carboxylate
  参考文献：
  名称：

  Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis

  摘要：

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.

  DOI：

  10.1021/jm300214e

文献信息

• Design, synthesis and evaluation of 3-phenoxypyrazine-2-carboxamide derivatives as potent TGR5 agonists
  作者：Shizhen Zhao、Le Wang、Jie Wang、Chenwei Wang、Shaowei Zheng、Yajie Fu、Yunfu Li、Wei-Dong Chen、Ruifang Hou、Dongbin Yang、Yan-Dong Wang

  DOI：10.1039/d1ra08867j

  日期：——

  TGR5 is emerging as an important and promising target for the treatment of non-alcoholic steatohepatitis, type 2 diabetes mellitus (T2DM), and obesity. A series of novel 3-phenoxypyrazine-2-carboxamide derivatives were designed, synthesized and evaluated in vitro and in vivo. The most potent compounds 18g and 18k exhibited excellent hTGR5 agonist activity, which was superior to those of the reference

  TGR5 正在成为治疗非酒精性脂肪性肝炎、2 型糖尿病 (T2DM) 和肥胖症的重要且有希望的靶点。设计、合成并在体外和体内评估了一系列新型 3-苯氧基吡嗪-2-甲酰胺衍生物。最有效的化合物18g和18k表现出优异的 hTGR5 激动剂活性，优于参考药物 INT-777。此外，化合物18k可显着降低 C57 BL/6 小鼠的血糖水平，并刺激 NCI-H716 细胞和 C57 BL/6 小鼠的 GLP-1 分泌。
• New Sulfanilamide Derivatives Incorporating Heterocyclic Carboxamide Moieties as Carbonic Anhydrase Inhibitors
  作者：Andrea Angeli、Victor Kartsev、Anthi Petrou、Mariana Pinteala、Roman M. Vydzhak、Svitlana Y. Panchishin、Volodymyr Brovarets、Viviana De Luca、Clemente Capasso、Athina Geronikaki、Claudiu T. Supuran

  DOI：10.3390/ph14080828

  日期：——

  of activity. We report here a novel series of sulfanilamide derivatives containing heterocyclic carboxamide moieties which were evaluated as CA inhibitors against the physiological relevant isoforms hCA I, II, IX, and XII. Some of them showed selectivity toward isoform hCA II and hCA XII. Molecular docking was performed for some of these compounds on isoforms hCA II and XII to understand the possible

  碳酸酐酶 (CA) 是普遍存在的金属酶，涉及多种疾病。有 15 种人类 CA (hCA) 亚型，它们的高度同源性对发现没有脱靶副作用的潜在药物提出了挑战。出于这个原因，正在进行许多合成和药理学研究工作，以实现 CA 活性调节剂的全部药理学潜力。我们在这里报告了一系列含有杂环甲酰胺部分的新型磺胺衍生物，这些衍生物被评估为针对生理相关亚型 hCA I、II、IX 和 XII 的 CA 抑制剂。其中一些对同种型 hCA II 和 hCA XII 显示出选择性。对这些化合物中的一些在同种型 hCA II 和 XII 上进行了分子对接，以了解与活性位点氨基酸残基的可能相互作用，
• [EN] COMPOSITIONS FOR INHIBITION OF HERPESVIRUSES<br/>[FR] COMPOSITIONS POUR L'INHIBITION DE VIRUS DE L'HERPÈS
  申请人：BOGER RAVIT

  公开号：WO2021150998A1

  公开（公告）日：2021-07-29

  The disclosure herein provides compounds of formulas I-V which are useful in the inhibition of viral diseases in a subject. In some embodiments, the compounds of formulas I-V are useful in the inhibition of herpes viruses.

  本公开提供了公式I-V的化合物，这些化合物对于抑制受试者体内的病毒性疾病是有用的。在某些实施方式中，公式I-V的化合物对于抑制疱疹病毒是有用的。
• Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus
  作者：Arun Kapoor、Ayan K. Ghosh、Michael Forman、Xin Hu、Wenjuan Ye、Noel Southall、Juan Marugan、Robert F. Keyes、Brian C. Smith、David J. Meyers、Marc Ferrer、Ravit Arav-Boger

  DOI：10.1021/acs.jmedchem.9b01501

  日期：2020.4.23

  The critical consequences of human cytomegalovirus (HCMV) infection in the transplant population and in congenitally infected infants, the limited treatment options for HCMV, and the rise of resistant mutants toward existing therapies has fueled the search for new anti-HCMV agents. A pp28-luciferase recombinant HCMV was used as a reporter system for high-throughput screening of HCMV inhibitors. Approximately 400 000 compounds from existing libraries were screened. Subsequent validation assays using resynthesized compounds, several virus strains, and detailed virology assays resulted in the identification of five structurally unique and selective HCMV inhibitors, active at sub to low micromolar concentrations. Further characterization revealed that each compound inhibited a specific stage of HCMV replication. One compound was also active against herpes simplex virus (HSV1 and HSV2), and another compound was active against Epstein-Barr virus (EBV). Drug combination studies revealed that all five compounds were additive with ganciclovir or letermovir. Future studies will focus on optimization of these new anti-HCMV compounds along with mechanistic studies.
• Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis
  作者：Janice A. Sindac、Bryan D. Yestrepsky、Scott J. Barraza、Kyle L. Bolduc、Pennelope K. Blakely、Richard F. Keep、David N. Irani、David J. Miller、Scott D. Larsen

  DOI：10.1021/jm300214e

  日期：2012.4.12

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.