methyl 2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate | 312950-39-3

• 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 2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
• 英文别名: Methyl 2-[(phenylcarbamothioyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate；methyl 2-(phenylcarbamothioylamino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• CAS: 312950-39-3
• 化学式: C₁₇H₁₈N₂O₂S₂
• mdl: MFCD01134356
• 分子量: 346.474
• InChiKey: AZTPNBVWBLYMPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 生成 2-疏基-3-苯基-5,6,7,8-四氢-3H-苯并[4,5]噻吩并[2,3-d]嘧啶-4-酮
  参考文献：
  名称：

  Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action

  摘要：

  From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.013
• 作为产物：
  描述：

  2-氨基-4,5,6,7-四氢苯并噻酚-3-羧酸乙酯 在 三乙胺 、 sodium hydroxide 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 20.0h， 生成 methyl 2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action

  摘要：

  From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.013

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。
• Design and synthesis of thiourea derivatives with sulfur-containing heterocyclic scaffolds as potential tyrosinase inhibitors
  作者：Pingping Liu、Chen Shu、Lujie Liu、Qingchun Huang、Yanqing Peng

  DOI：10.1016/j.bmc.2016.03.013

  日期：2016.4

  animals. A class of novel N-aryl-N′-substituted phenylthiourea derivatives (3a–i, 6a–k) were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed some 4,5,6,7-tetrahydro-2-[[(phenylamino)thioxomethyl]amino]-benzo[b]thiophene-3-carboxylic acid derivatives (3a–i) exhibited moderate inhibitory potency on diphenolase activity

  酪氨酸酶是植物和动物体内黑色素生成过程中的关键酶。设计，合成了一类新型的N-芳基-N'-取代的苯硫脲衍生物（3a – i，6a – k），并评价了它们对蘑菇酪氨酸酶双酚酶活性的抑制作用。结果表明，某些4,5,6,7-四氢-2-[[[（（苯基氨基）硫代甲基]氨基]-苯并[ b ]噻吩-3-羧酸衍生物（3a – i）对中和酚的双酚酶活性具有中等抑制作用。酪氨酸酶。当4,5,6,7-四氢苯并[ b用2-（1,3,4-噻二唑-2-基）硫代乙酸代替]噻吩-3-羧酸，化合物（6a - k）对酪氨酸酶的抑制作用明显提高。特别是化合物6h（IC 50  = 6.13μM）的抑制活性明显高于曲酸（IC 50  = 33.3μM）。此外，对抑制机理的分析表明，化合物6h可能起非竞争性抑制剂的作用。
• COMPOSITIONS AND METHODS FOR LUNG REGENERATION
  申请人：AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)

  公开号：US20150125490A1

  公开（公告）日：2015-05-07

  Described herein are stein cells and related factors for treating degenerative and inflammatory disorders of lung tissue.
• USE OF TOLL-LIKE RECEPTOR 2 (TLR-2) AGONIST FOR MODULATING HUMAN IMMUNE RESPONSE
  申请人：Children's Medical Center Corporation

  公开号：US20210236632A1

  公开（公告）日：2021-08-05

  Provided herein are Toll-like receptor 2 (TLR2) agonists for use in enhancing human immune response and/or as adjuvants in vaccines. The TLR2 agonists include thiophenes, imidazoles, or phenyl-containing compounds, which may be compounds of Formulae (I), (II), (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein are used as enhancers of an immune response (e.g., innate and/or adaptive immune response), and are useful in treating and/or preventing a disease, as adjuvants in a vaccine for the disease, (e.g., proliferative disease, inflammatory disease, autoimmune disease, infectious disease, or chronic disease). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
• Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action
  作者：Jonathan E. Hempel、Adrian G. Cadar、Charles C. Hong

  DOI：10.1016/j.bmcl.2016.03.013

  日期：2016.4

  From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation. Published by Elsevier Ltd.