2-羟基-5-硫脲基苯甲酸 | 728918-63-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-羟基-5-硫脲基苯甲酸
• 英文名称: 2-hydroxy-5-thioureido-benzoic acid
• 英文别名: 5-Thioureido-salicylsaeure；2-Hydroxy-5-thioureido-benzoesaeure；2-Hydroxy-5-thioureidobenzoic acid；5-(carbamothioylamino)-2-hydroxybenzoic acid
• CAS: 728918-63-6
• 化学式: C₈H₈N₂O₃S
• 分子量: 212.229
• InChiKey: RBBIOYKZQUEJHZ-UHFFFAOYSA-N

物化性质

• 沸点：
  434.2±55.0 °C(Predicted)
• 密度：
  1.651±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  2-羟基-5-硫脲基苯甲酸 、 2-bromo-1-(4-fluoro-3-methyl-phenyl)-ethanone 以 乙醇 为溶剂， 反应 2.0h， 以88%的产率得到5-(4-(4-fluoro-3-methylphenyl)thiazol-2-ylamino)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Identification of a novel selective small-molecule inhibitor of protein arginine methyltransferase 5 (PRMT5) by virtual screening, resynthesis and biological evaluations

  摘要：

  As one of the most promising anticancer target in protein arginine methyltransferase (PRMT) family, PRMT5 has been drawing more and more attentions, and many efforts have been devoted to develop its inhibitors. In this study, three PRMT5 inhibitors (9, 16, and 23) with novel scaffolds were identified by performing pharmacophore-and docking-based virtual screening combined with in vitro radiometric- based scintillation proximity assay (SPA). Substructure search based on the scaffold of the most active 9 afforded 26 additional analogues, and SPA results indicated that two analogues (9-1 and 9-2) showed increased PRMT5 inhibitory activity compared with the parental compound. Resynthesis of 9, 9-1, and 92 confirmed their PRMT5 enzymatic inhibition activity. In addition, compound 9-1 displayed selectivity against PRMT5 over other key homological members (PRMT1 and CARM1 (PRMT4)). While the structureactivity relationship (SAR) of this series of compounds was discussed to provide clues for further structure optimization, the probable binding modes of active compounds were also probed by molecular docking and molecular dynamics simulations. Finally, the antiproliferative effect of 9-1 on MV4-11 leukemia cell line was confirmed and its impact on regulating the target gene of PRMT5 was also validated. The hit compounds identified in this work have provided more novel scaffolds for future hit-to-lead optimization of small-molecule PRMT5 inhibitors. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.087
• 作为产物：
  描述：

  5-氨基水杨酸 、 苯甲酰基异硫氰酸酯 在 sodium methylate 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 以73 %的产率得到2-羟基-5-硫脲基苯甲酸
  参考文献：
  名称：

  4-Trifluoromethyl bithiazoles as broad-spectrum antimicrobial agents for virus-related bacterial infections or co-infections

  摘要：

  Is magic trifluoromethyl a thing? Replacing 4-CH₃ with 4-CF₃ in bithiazoles, allowed to identify broad antimicrobial agents active against multiple viruses and also against Gram-positive/negative bacteria.

  DOI：

  10.1039/d3md00686g

文献信息

• IDO Inhibitors
  申请人：Mautino Mario

  公开号：US20110053941A1

  公开（公告）日：2011-03-03

  Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; and (f) treating immunosuppression associated with an infectious disease, e.g., HIV-I infection, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount a compound as described in one of the aspects described herein.

  目前提供以下方法：(a) 通过接触本文中描述的化合物的调节有效量与吲哚胺2,3-二氧化酶相互作用，从而调节吲哚胺2,3-二氧化酶的活性；(b) 治疗需要吲哚胺2,3-二氧化酶(IDO)介导的免疫抑制的患者，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(c) 治疗需要抑制吲哚胺-2,3-二氧化酶酶活性的医疗状况，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(d) 增强抗癌治疗的有效性，包括给予抗癌剂和本文中描述的化合物；(e) 治疗与癌症相关的肿瘤特异性免疫抑制，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(f) 治疗与传染病相关的免疫抑制，例如HIV-1感染，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量。
• Thiazolidinone CFTR inhibitors with improved water solubility identified by structure–activity analysis
  作者：N.D. Sonawane、A.S. Verkman

  DOI：10.1016/j.bmc.2008.07.044

  日期：2008.9

  The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator ( CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modi. cations in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with similar to 1 mu M CFTR inhibition potency and solubility >180 mu M(>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease. (C) 2008 Elsevier Ltd. All rights reserved.
• DE377412
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification of a novel selective small-molecule inhibitor of protein arginine methyltransferase 5 (PRMT5) by virtual screening, resynthesis and biological evaluations
  作者：Kongkai Zhu、Chengshi Jiang、Hongrui Tao、Jingqiu Liu、Hua Zhang、Cheng Luo

  DOI：10.1016/j.bmcl.2018.03.087

  日期：2018.5

  As one of the most promising anticancer target in protein arginine methyltransferase (PRMT) family, PRMT5 has been drawing more and more attentions, and many efforts have been devoted to develop its inhibitors. In this study, three PRMT5 inhibitors (9, 16, and 23) with novel scaffolds were identified by performing pharmacophore-and docking-based virtual screening combined with in vitro radiometric- based scintillation proximity assay (SPA). Substructure search based on the scaffold of the most active 9 afforded 26 additional analogues, and SPA results indicated that two analogues (9-1 and 9-2) showed increased PRMT5 inhibitory activity compared with the parental compound. Resynthesis of 9, 9-1, and 92 confirmed their PRMT5 enzymatic inhibition activity. In addition, compound 9-1 displayed selectivity against PRMT5 over other key homological members (PRMT1 and CARM1 (PRMT4)). While the structureactivity relationship (SAR) of this series of compounds was discussed to provide clues for further structure optimization, the probable binding modes of active compounds were also probed by molecular docking and molecular dynamics simulations. Finally, the antiproliferative effect of 9-1 on MV4-11 leukemia cell line was confirmed and its impact on regulating the target gene of PRMT5 was also validated. The hit compounds identified in this work have provided more novel scaffolds for future hit-to-lead optimization of small-molecule PRMT5 inhibitors. (C) 2018 Elsevier Ltd. All rights reserved.
• 4-Trifluoromethyl bithiazoles as broad-spectrum antimicrobial agents for virus-related bacterial infections or co-infections
  作者：Francesca Barbieri、Vincent Carlen、Maria Grazia Martina、Filomena Sannio、Sacha Cancade、Cecilia Perini、Margherita Restori、Emmanuele Crespan、Giovanni Maga、Jean-Denis Docquier、Valeria Cagno、Marco Radi

  DOI：10.1039/d3md00686g

  日期：——

  Is magic trifluoromethyl a thing? Replacing 4-CH₃ with 4-CF₃ in bithiazoles, allowed to identify broad antimicrobial agents active against multiple viruses and also against Gram-positive/negative bacteria.