isopropyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate | 329222-97-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: isopropyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
• 英文别名: 2-Amino-6-methyl-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid isopropyl ester；propan-2-yl 2-amino-6-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• CAS: 329222-97-1
• 化学式: C₁₃H₁₉NO₂S
• mdl: MFCD00783380
• 分子量: 253.365
• InChiKey: PMEGAOJOWAZQLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.615
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  isopropyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 isopropyl 2-(2-(2-imino-4-oxothiazolidin-5-yl)acetamido)-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups

  摘要：

  N-甲基-d-天冬氨酸受体（NMDAR）是大脑中的一种重要受体，与多种神经系统疾病有关。许多非选择性 NMDAR 靶向药物的耐受性都很差，因此人们努力靶向 NMDAR 亚型以提高治疗指数。我们在此介绍了一系列在饱和浓度下具有亚最大抑制作用的负异构 NMDAR 调节剂。化学结构的适度变化可将负调制与正调制相互转换。所有调节剂都具有增强激动剂效力的能力，并且具有使用依赖性，在调节剂发挥高效力之前需要同时与两种激动剂结合。数据表明，这些调节剂（包括两种对映体）与受体上的相同位点结合，并具有共同的作用结构决定因素。由于调制剂的特性，该系列中的亚最大负性调制剂可能会使突触处的 NMDAR 免受影响，同时增强 NMDAR 在突触外空间的反应。这些调节剂可作为探究突触外 NMDAR 作用的有用工具。

  DOI：

  10.7554/elife.34711
• 作为产物：
  描述：

  氰乙酸异丙酯 、 4-甲基环己酮 在 吗啉 、 sulfur 作用下， 以 异丙醇 为溶剂， 以98%的产率得到isopropyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups

  摘要：

  N-甲基-d-天冬氨酸受体（NMDAR）是大脑中的一种重要受体，与多种神经系统疾病有关。许多非选择性 NMDAR 靶向药物的耐受性都很差，因此人们努力靶向 NMDAR 亚型以提高治疗指数。我们在此介绍了一系列在饱和浓度下具有亚最大抑制作用的负异构 NMDAR 调节剂。化学结构的适度变化可将负调制与正调制相互转换。所有调节剂都具有增强激动剂效力的能力，并且具有使用依赖性，在调节剂发挥高效力之前需要同时与两种激动剂结合。数据表明，这些调节剂（包括两种对映体）与受体上的相同位点结合，并具有共同的作用结构决定因素。由于调制剂的特性，该系列中的亚最大负性调制剂可能会使突触处的 NMDAR 免受影响，同时增强 NMDAR 在突触外空间的反应。这些调节剂可作为探究突触外 NMDAR 作用的有用工具。

  DOI：

  10.7554/elife.34711

文献信息

• 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。
• Structure-Based Virtual Screening, Compound Synthesis, and Bioassay for the Design of Chitinase Inhibitors
  作者：Yawen Dong、Xi Jiang、Tian Liu、Yun Ling、Qing Yang、Li Zhang、Xiongkui He

  DOI：10.1021/acs.jafc.8b00017

  日期：2018.4.4

  Chitinases play a vital part in the molting phase of insect pests. Inhibiting their activities by the use of drug-like small chemical molecules is thought to be an efficient strategy in pesticide design and development. On the basis of the crystal structure of Of ChtI, a chitinase indispensable for the molting of the insect pest Ostrinia furnacalis (Asian corn borer), here we report a chemical fragment and five variant compounds as inhibitors of Of ChtI obtained from a library of over 200 000 chemicals by a structure-based-virtual-screening approach. The compounds were synthesized with high atom economy and tested for their. Of ChtI-inhibitory activities in a bioassay. Compound 3 showed preferential inhibitory activity with a K-i value of 1.5 mu M against Of ChtI. Analysis of the structure-activity relationships of the compounds provided insight into their interactions with the enzyme active site, which may inform future work in improving the potencies of their inhibitory activities.
• 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives and methods for medical intervention against mycobacterial infections
  申请人：Missio Andrea

  公开号：US20090018149A1

  公开（公告）日：2009-01-15

  Described are 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives and pharmaceutically acceptable salts thereof, the use of these derivatives for the prophylaxis and/or treatment of mycobacteria-induced infections and opportunistic infections, as well as compositions containing at least one 4,5,6,7-tetrahydrobenzo[b]thiophene derivative and/or pharmaceutically acceptable salts thereof. Furthermore, the present application refers to the use of mycobacterial protein serine/threonine kinases for developing methods for detection and determination of these kinases for recognising and monitoring diseases and for controlling therapy of diseases.
• Design, Synthesis, and Structure–Activity Relationship of <i>N</i>-Aryl-<i>N</i>′-(thiophen-2-yl)thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
  作者：Zhipeng Chen、Lina Zhang、Junjie Yang、Lu Zheng、Fanjie Hu、Siqin Duan、Kutty Selva Nandakumar、Shuwen Liu、Hang Yin、Kui Cheng

  DOI：10.1021/acs.jmedchem.0c02266

  日期：2021.6.10

  cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release

  之前对 1000 万种化合物的虚拟筛选产生了两种新的非脂肽样化学型作为 TLR2 激动剂。在此，我们介绍了我们最初命中的 1-苯基-3-(噻吩-2-基) 脲的化学优化，这导致将 SMU-C80 (EC 50 = 31.02 ± 1.01 nM)鉴定为 TLR2 特异性生物活性提高 370 倍的激动剂。机理研究表明，SMU-C80 通过 TLR1/2 募集接头蛋白 MyD88 并触发 NF-κB 通路以从人类而非鼠类细胞中释放细胞因子，例如 TNF-α 和 IL-1β。据我们所知，它是迄今为止报道的第一个物种特异性 TLR1/2 激动剂。此外，SMU-C80 增加了离体T、B 和 NK 细胞的百分比并激活免疫细胞，从而抑制体外癌细胞的生长。总之，我们获得了一种高效且特异的人 TLR1/2 激动剂，它通过 MyD88 和 NF-κB 途径起作用，促进细胞因子的释放和免疫细胞的同时激活，进而影响癌细胞的凋亡。
• An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups
  作者：Riley Perszyk、Brooke M Katzman、Hirofumi Kusumoto、Steven A Kell、Matthew P Epplin、Yesim A Tahirovic、Rhonda L Moore、David Menaldino、Pieter Burger、Dennis C Liotta、Stephen F Traynelis

  DOI：10.7554/elife.34711

  日期：——

  N-methyl-d-aspartate receptors (NMDARs) are an important receptor in the brain and have been implicated in multiple neurological disorders. Many non-selective NMDAR-targeting drugs are poorly tolerated, leading to efforts to target NMDAR subtypes to improve the therapeutic index. We describe here a series of negative allosteric NMDAR modulators with submaximal inhibition at saturating concentrations. Modest changes to the chemical structure interconvert negative and positive modulation. All modulators share the ability to enhance agonist potency and are use-dependent, requiring the binding of both agonists before modulators act with high potency. Data suggest that these modulators, including both enantiomers, bind to the same site on the receptor and share structural determinants of action. Due to the modulator properties, submaximal negative modulators in this series may spare NMDAR at the synapse, while augmenting the response of NMDAR in extrasynaptic spaces. These modulators could serve as useful tools to probe the role of extrasynaptic NMDARs.

  N-甲基-d-天冬氨酸受体（NMDAR）是大脑中的一种重要受体，与多种神经系统疾病有关。许多非选择性 NMDAR 靶向药物的耐受性都很差，因此人们努力靶向 NMDAR 亚型以提高治疗指数。我们在此介绍了一系列在饱和浓度下具有亚最大抑制作用的负异构 NMDAR 调节剂。化学结构的适度变化可将负调制与正调制相互转换。所有调节剂都具有增强激动剂效力的能力，并且具有使用依赖性，在调节剂发挥高效力之前需要同时与两种激动剂结合。数据表明，这些调节剂（包括两种对映体）与受体上的相同位点结合，并具有共同的作用结构决定因素。由于调制剂的特性，该系列中的亚最大负性调制剂可能会使突触处的 NMDAR 免受影响，同时增强 NMDAR 在突触外空间的反应。这些调节剂可作为探究突触外 NMDAR 作用的有用工具。