2-(4-chloro)benzamide-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester | 52535-71-4

• 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: 2-(4-chloro)benzamide-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester
• 英文别名: 2-(4-chloro-benzoylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester；Benzo(b)thiophene-3-carboxylic acid, 4,5,6,7-tetrahydro-2-((4-chlorobenzoyl)amino)-, ethyl ester；ethyl 2-[(4-chlorobenzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• CAS: 52535-71-4
• 化学式: C₁₈H₁₈ClNO₃S
• mdl: MFCD00264856
• 分子量: 363.865
• InChiKey: VEBJXARNPPZDKS-UHFFFAOYSA-N

物化性质

• 熔点：
  137 °C(Solv: ethanol (64-17-5); benzene (71-43-2))
• 沸点：
  472.9±45.0 °C(Predicted)
• 密度：
  1.342±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-chloro)benzamide-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 4-chloro-N-(4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-benzamide
  参考文献：
  名称：

  Functional derivatives of thiophene

  摘要：

  DOI：

  10.1007/bf00477559
• 作为产物：
  描述：

  乙酰乙酸乙酯 在 吗啉 、 sulfur 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-(4-chloro)benzamide-6-ethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  四氢苯并噻吩类化合物及药物组合物的制备方法和用途

  摘要：

  本发明属于医药领域，具体涉及一种四氢苯并噻吩类化合物及药物组合物和其制备方法和用途。四氢苯并噻吩类化合物为如式I所示化合物I；其中，R1和R2为C1‑4饱和/不饱和烃基、‑OCH3、‑OCH2CH3、苯基、取代苯基、‑NO2、‑COR、‑OH、‑F、‑Cl、‑Br、‑I、‑H其中的一种；R1与R2相同或不同；R3为‑F、‑Cl、‑Br、‑I、‑OH、氨基、C1‑4饱和/不饱和烃基、‑OCH3、‑OCH2CH3、‑H其中的一种；n≥5，n为整数。该化合物通过抑制脂多糖合成通路中的ATP依赖性转运蛋白的合成，有效抑制沙门氏菌、铜绿假单胞菌、抗大肠杆菌、抗金黄色葡萄球菌。

  公开号：

  CN113501807A

文献信息

• Design, Synthesis, and Anti-Bacterial Evaluation of Tetrahydrobenzothiophene Derivatives as Lipopolysaccharide Biogenesis Inhibitors
  作者：Jun Chen、Shuchen Pei、Jinhua Yang、Shihao Xia、Shuting Tang、Kangyao Yuan

  DOI：10.2174/1570180819666220317151208

  日期：2023.3

  Bacterial infections caused by multidrug-resistant bacteria have emerged as major threats to human communities worldwide. There is a great need to develop new mechanisms by which anti-bacterial agents can combat bacterial antibiotic resistance.

  This study aims to synthesize and characterize a series of novel tetrahydrobenzothiophene derivatives and evaluate their anti-bacterial activities.

  In this study, we have synthesized 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxylic acid derivatives (3a-3r) and investigated their anti-bacterial activities against E. coli, P. aeruginosa, Salmonella, and S. aureus.

  The MIC values demonstrated that all synthesized derivatives possessed potent anti-bacterial activity properties. Compounds 3b, 3e, 3f, 3g, 3h, 3n, and 3q exhibited in vitro excellent anti-bacterial efficiency. Compounds 3b, 3e, 3f, and 3p were evaluated by in vitro time-kill assay; they displayed concentration- dependent bacteriostatic effects. Compounds 3b, 3e, 3f, and 3p showed moderate water solubility, high stability in plasma, and moderate acute oral toxicity.

  Most of the 2-benzamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid derivatives exhibited potent anti-bacterial activities. The data reported in this paper may guide the design of tetrahydrobenzothiophene derivatives.

  背景：多药耐药细菌引起的细菌感染已经成为全球人类社区的主要威胁。迫切需要开发新的机制来对抗细菌抗生素耐药性。 目的：本研究旨在合成和表征一系列新型四氢苯并噻吩衍生物，并评估它们的抗菌活性。 方法：在本研究中，我们合成了2-苯甲酰胺-4,5,6,7-四氢苯并[b]噻吩-3-羧酸衍生物（3a-3r），并研究了它们对大肠杆菌、铜绿假单胞菌、沙门氏菌和金黄色葡萄球菌的抗菌活性。 结果：最小抑菌浓度（MIC）值表明，所有合成的衍生物都具有强大的抗菌活性。化合物3b、3e、3f、3g、3h、3n和3q表现出极好的体外抗菌效率。化合物3b、3e、3f和3p经过体外时间杀菌实验评估，它们显示出浓度依赖的细菌抑制效果。化合物3b、3e、3f和3p表现出中等的水溶性，高稳定性和中等的急性口服毒性。 结论：大多数2-苯甲酰胺-4,5,6,7-四氢苯并[b]噻吩-3-羧酸衍生物表现出强大的抗菌活性。本文报告的数据可以指导四氢苯并噻吩衍生物的设计。
• Novel therapeutic targets for the treatment of mycobacterial infections and compounds useful therefor
  申请人：——

  公开号：US20040171603A1

  公开（公告）日：2004-09-02

  Described herein is the discovery that certain mycobacterial serine/threonine protein kinases, particularly protein kinase G (PknG), are effective therapeutic targets for the treatment of mycobacterial infections. Furthermore, the present application refers to the use of mycobacterial serine/threonine protein kinases for developing methods for detection and determination of these kinases for recognizing and monitoring diseases and for controlling therapy of diseases. Additionally disclosed are novel 4,5,6,7-tetrahydrobenzo[b]thiophene compounds, benzo(g)quinoxaline compounds, and pharmaceutically acceptable salts thereof, and methods of using such compounds and salts thereof for the prophylaxis and/or treatment of virally and/or bacterially induced infections, particularly mycobacteria-induced infections, including opportunistic infections, as well as pharmaceutical compositions containing at least one 4,5,6,7-tetrahydrobenzo[b]thiophene compound and/or benzo(g)quinoxaline compound and/or pharmaceutically acceptable salts thereof in a pharmaceutically acceptable carrier.

  本文描述的是发现某些分枝杆菌丝氨酸/苏氨酸蛋白激酶，特别是蛋白激酶 G (PknG)，是治疗分枝杆菌感染的有效治疗靶点。此外，本申请还涉及利用分枝杆菌丝氨酸/苏氨酸蛋白激酶开发检测和测定这些激酶的方法，用于识别和监测疾病以及控制疾病的治疗。此外，还公开了新型 4,5,6,7-四氢苯并[b]噻吩化合物、苯并（g）喹喔啉化合物及其药学上可接受的盐，以及使用此类化合物及其盐预防和/或治疗病毒和/或细菌引起的感染，特别是分枝杆菌引起的感染（包括机会性感染）的方法，以及含有至少一种 4,5,6,7-四氢苯并&lsqb；b]噻吩化合物和/或苯并(g)喹喔啉化合物和/或其药学上可接受的盐，并将其置于药学上可接受的载体中。
• Perrissin; Duc; Narcisse, European Journal of Medicinal Chemistry, 1980, vol. 15, # 5, p. 413 - 418
  作者：Perrissin、Duc、Narcisse、et al.

  DOI：——

  日期：——
• PERRISSIN M.; LUU DUC C.; NARCISSE G.; BAKRI-LOGEAIS F.; HUGUET F., EUR. J. MED. CHEM.-CHIM. THER., 1980, 15, NO 5, 413-418
  作者：PERRISSIN M.、 LUU DUC C.、 NARCISSE G.、 BAKRI-LOGEAIS F.、 HUGUET F.

  DOI：——

  日期：——
• Synthesis and Anti‐Inflammatory Activity of 2‐Amino‐4,5,6,7‐tetrahydrobenzo[ <i>b</i> ]thiophene‐Derived NRF2 Activators
  作者：Kit‐Kay Mak、Zhang Shiming、Ola Epemolu、Albena T. Dinkova‐Kostova、Geoffrey Wells、Irina G. Gazaryan、Raghavendra Sakirolla、Zulkefeli Mohd、Mallikarjuna Rao Pichika

  DOI：10.1002/open.202200181

  日期：2022.10

  AbstractThis is the first study investigating the nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) activity of compounds containing a new scaffold, tetrahydrobenzo[b]thiophene. Eighteen compounds were synthesised and confirmed their NRF2 activation through NQO1 enzymatic activity and mRNA expression of NQO1 and HO‐1 in Hepa‐1c1c7 cells. The compounds disrupted the interaction between Kelch‐like ECH‐associated protein 1 (KEAP1) and NRF2 via interfering with the KEAP1’s Kelch domain. The compounds exhibited anti‐inflammatory activity in Escherichia coli Lipopolysaccharide (LPSEc)‐stimulated RAW 264.7 cells. The anti‐inflammatory activity of the compounds was associated with their ability to activate NRF2. The compounds reversed the elevated levels of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and IFN‐γ) and inflammatory mediators (PGE2, COX‐2, and NF‐κB). The compounds were metabolically stable in human, rat, and mouse liver microsomes and showed optimum half‐life (T1/2) and intrinsic clearance (Clint). The binding mode of the compounds and physicochemical properties were predicted via in silico studies.