isopropyl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate | 351983-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环七噻吩
• 英文名称: isopropyl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate
• 英文别名: propan-2-yl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate
• CAS: 351983-32-9
• 化学式: C₁₃H₁₉NO₂S
• mdl: MFCD01114971
• 分子量: 253.365
• InChiKey: WUJCNUNGGPFMTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 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

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  isopropyl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-(4-methylpiperazine-1-thiocarboxamido)-5,6,7,8-tetrahydro-4H-cyclohepteno[b]thiophene-3-carboxylic acid isopropyl ester
  参考文献：
  名称：

  Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors

  摘要：

  Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as toll-like receptor 2 (TLR2) agonists. In this report, compounds belonging to four areas of structural modification of ZINC6662436 were evaluated for biological activity using human HEK-Blue TLR2 reporter cells, and human THP-1 monocytic cells, yield SMU-C13 as an optimized, direct and high potent (EC50 = 160 nM) agonist of human TLR2. Moreover, preliminary mechanism studies indicated that SMU-C13 through activates TLR1 and TLR2 then stimulates the NF-kappa B activation to trigger the downstream cytokines, such as TNF-alpha and secreted alkaline phosphatase (SEAP). (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.067
• 作为产物：
  描述：

  氰乙酸异丙酯 、 环庚酮 在 sulfur 、 N-甲基吗啉 作用下， 以 乙醇 为溶剂， 反应 24.17h， 生成 isopropyl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate
  参考文献：
  名称：

  通过从头设计，合成和生物学评估，设计基于结构的选择性SHP2抑制剂。

  摘要：

  PTPN11基因编码的SHP2磷酸酶是一种非受体PTP，在生长因子，细胞因子，整联蛋白，激素信号传导途径中起着重要作用，并调节细胞反应，例如增殖，分化，粘附迁移和凋亡。许多研究报告说，SHP2表达的上调与人类癌症（如乳腺癌，肝癌和胃癌）密切相关。因此，SHP2已成为癌症免疫疗法的有希望的靶标。在本文中，我们报道了化合物1作为SHP2抑制剂的鉴定。进行了基于片段的配体设计，从头设计，ADMET和分子对接，以探索基于SHP836的潜在选择性SHP2变构抑制剂。对接研究的结果表明，所选化合物比现有抑制剂具有更高的选择性SHP2抑制作用。发现化合物1具有针对SHP2的新选择性，其体外酶活性IC50值为9.97μM。荧光滴定实验证实化合物1直接与SHP2结合。此外，结合自由能的结果表明，静电能是阐明SHP2抑制机理的主要因素。动态互相关研究也支持对接和分子动力学模拟的结果。这一系列分析为设计新的选择

  DOI：

  10.1007/s10822-019-00213-z

文献信息

• 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。
• A new class of small molecule RNA polymerase inhibitors with activity against Rifampicin-resistant Staphylococcus aureus1
  作者：Francis Arhin、Odette Bélanger、Stéphane Ciblat、Mohammed Dehbi、Daniel Delorme、Evelyne Dietrich、Dilip Dixit、Yanick Lafontaine、Dario Lehoux、Jing Liu、Geoffrey A. McKay、Greg Moeck、Ranga Reddy、Yannick Rose、Ramakrishnan Srikumar、Kelly S.E. Tanaka、Daniel M. Williams、Philippe Gros、Jerry Pelletier、Thomas R. Parr、Adel Rafai Far

  DOI：10.1016/j.bmc.2006.05.035

  日期：2006.9

  The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase. (c) 2006 Elsevier Ltd. All rights reserved.