4-氟-2-甲基硫代苯并噻唑 | 154327-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 4-氟-2-甲基硫代苯并噻唑
• 英文名称: 4-fluoro-2-(methylthio)benzo[d]thiazole
• 英文别名: 4-fluoro-2-(methylthio)benzothiazole；2-methylthio-4-fluoro-benzothiazole；4-fluoro-2-methylsulfanyl-1,3-benzothiazole
• CAS: 154327-25-0
• 化学式: C₈H₆FNS₂
• mdl: MFCD12756452
• 分子量: 199.273
• InChiKey: PDJMWBTVBFQLAY-UHFFFAOYSA-N

物化性质

• 熔点：
  37.1-37.4 °C
• 沸点：
  306.5±34.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934200090

反应信息

• 作为反应物：
  描述：

  4-氟-2-甲基硫代苯并噻唑 在 苯甲醚 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.0h， 生成 (2Z,5E)-3-ethyl-5-(4-fluoro-3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-(pyridin-2-ylmethylene)thiazolidin-4-one
  参考文献：
  名称：

  具有增强代谢稳定性的热休克蛋白 70 (Hsp70) 抑制剂可降低 tau 水平

  摘要：

  分子伴侣热休克蛋白 70 (Hsp70) 是一种新兴的神经退行性疾病药物靶点，因为它能够促进微管相关蛋白 tau (MAPT/tau) 的降解。最近，我们报道了 YM-08 作为脑渗透剂、变构 Hsp70 抑制剂，可降低 tau 水平。然而，YM-08 的苯并噻唑部分易受 CYP3A4 代谢的影响，限制了其作为化学探针的进一步应用。在这篇手稿中，我们通过将卤素原子系统地引入苯并噻唑环并改变末端吡啶中杂原子的位置，设计并合成了 17 种 YM-08 衍生物。在微粒体测定中，我们发现化合物 JG-23 的代谢稳定性提高了 12 倍，并且在两种基于细胞的模型中保留了降低 tau 水平的能力。

  DOI：

  10.1016/j.bmcl.2021.128025
• 作为产物：
  描述：

  2-氯-6-氟苯胺 在 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-氟-2-甲基硫代苯并噻唑
  参考文献：
  名称：

  Analogues of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, As Anti-Cancer Agents

  摘要：

  The rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chemical probe or potential therapeutic. We report the synthesis and characterization of MKT-077 analogues designed for greater stability. The most potent molecules, such as 30 (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 +/- 0.03 and 0.7 +/- 0.2 mu M, respectively). The analogues modestly destabilized the chaperone clients, Aka and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t(1/2) = 37 min) compared to MKT-077 (t(1/2) < 5 min). Finally, NMR titration experiments suggested that these analogues bind an allosteric site that is known to accommodate MKT-077. These studies advance MKT-077 analogues as chemical probes for studying Hsp70s roles in cancer.

  DOI：

  10.1021/ml400204n

文献信息

• General Entry into <i>o</i> -,<i>o′</i> -Heteroatom-Linked <i>N</i> -(Hetero)aryl-Imidazole Motifs by Gold-Catalysed Formal [3+2]-Dipolar Cycloaddition
  作者：Miguel Garzón、Elsa M. Arce、Raju Jannapu Reddy、Paul W. Davies

  DOI：10.1002/adsc.201700249

  日期：2017.6.6

  general redox‐neutral approach into the o‐,o′‐heteroatom‐linked N‐(hetero)aryl‐imidazole family of heteroaromatics has been developed. New types of heteroatom substituted carbimidoyl nitrenoids are efficiently realised from robust, bench‐stable N‐(heteroaryl)‐pyridinium‐N‐aminides by formal gold‐catalysed [3+2]‐dipolar cycloadditions across ynamides. Broad structural variety and functional group tolerance

  已开发出一种将杂芳烃的邻，邻杂原子连接的N-（杂）芳基-咪唑家族的氧化还原中性方法。新型的杂原子取代的碳酰亚胺基亚硝基化合物可以通过稳定的，稳定的N-（杂芳基）-吡啶鎓-N-胺类化合物，通过正式的金催化的[3 + 2]-偶极环加成酰胺类有效地实现。广泛的结构多样性和官能团耐受性允许快速进入各种功能化的支架，如制备8个不同的杂芳族核心所示。
• New herbicidal fluorobenzothiazolyloxyacetamides
  申请人：Bayer Aktiengesellschaft

  公开号：US05356864A1

  公开（公告）日：1994-10-18

  Novel herbicidal fluorobenzothiazolyloxyacetamides of the formula ##STR1## in which R.sup.1 represents hydrogen or an optionally substituted radical from the group consisting of alkyl, alkenyl, alkinyl and aralkyl, R.sup.2 represents an optionally substituted radical from the group consisting of alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkenyl, aralkyl, aryl, alkoxy, alkenyloxy or alkinyloxy, or R.sup.1 and R.sup.2, together with the nitrogen atom to which they are bonded, form an optionally substituted, saturated or unsaturated nitrogen heterocycle which can contain further heteroatoms and to which a benzo group can be fused.

  化学式为##STR1##的新型除草药物氟苯并噻唑氧基乙酰胺，其中R.sup.1代表氢或选自烷基，烯基，炔基和芳基烷基等基团的可选择性取代基团，R.sup.2代表选自烷基，烯基，炔基，环烷基，环烯基，芳基烷基，芳基，烷氧基，烯氧基或炔氧基的可选择性取代基团，或者R.sup.1和R.sup.2与它们连接的氮原子一起形成可选择性取代的饱和或不饱和氮杂环，该氮杂环可以含有更多的杂原子，并且可以与苯并环结合。
• Fluorbenzthiazolyloxyacetamide
  申请人：BAYER AG

  公开号：EP0588183A1

  公开（公告）日：1994-03-23

  Die Erfindung betrifft neue Fluorbenzthiazolyloxyacetamide der Formel (I), in welcher R¹für Wasserstoff oder für einen gegebenenfalls substituierten Rest aus der Reihe Alkyl, Alkenyl, Alkinyl oder Aralkyl steht, R²für einen gegebenenfalls substituierten Rest aus der Reihe Alkyl, Alkenyl, Alkinyl, Cycloalkyl, Cycloalkenyl, Aralkyl, Aryl, Alkoxy, Alkenyloxy oder Alkinyloxy steht, oder R¹ und R²zusammen mit dem Stickstoffatom, an welches sie gebunden sind, einen gegebenenfalls substituierten, gesättigten oder ungesättigten Stickstoff-Heterocyclus bilden, der weitere Heteroatome enthalten kann und an den eine Benzo-Gruppierung anelliert sein kann, ein Verfahren und neue Zwischenprodukte zu ihrer Herstellung sowie ihre Verwendung als Herbizide.

  本发明涉及式 (I) 的新型氟苯并噻唑基氧基乙酰胺、 其中 R¹代表氢或由烷基、烯基、炔基或芳烷基组成的系列中的任选取代基、 R² 代表由烷基、烯基、炔基、环烷基、环烯基、芳基、烷氧基、烯氧基或炔氧基组成的系列中的任选取代基，或 R¹和 R²与它们所结合的氮原子一起形成任选取代的饱和或不饱和氮杂环，该杂环可含有更多的杂原子，并可与苯并基团融合、 制备它们的工艺和新中间体，以及它们作为除草剂的用途。
• Novel KCNQ2/Q3 Agonists as Potential Therapeutics for Epilepsy and Neuropathic Pain
  作者：Paul C. Fritch、Grant McNaughton-Smith、George S. Amato、James F. Burns、C. Wesley Eargle、Rosemarie Roeloffs、William Harrison、Leslie Jones、Alan D. Wickenden

  DOI：10.1021/jm901497b

  日期：2010.1.28

  Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GABAergic activity and thus a number of associated side effects. Modulation of the M-current through opening of KCNQ channels has been proposed as a way to attenuate neuroexcitability and have a therapeutic benefit for the treatment Of seizure disorders. Therefore, as part Of our program to identify new treatments for epilepsy, we set out to identify agonists of KCNQ channels. High throughput screening of our corporate collection led to the identification of 1, adamantane-1-carboxylic acid (3-methyl-3H-benzothiazol-2-ylidine) hydrazide, a potent KCNQ2/Q3 agonist. Herein, we describe the syntheses and structure-activity relationships of analogues of I its well as their in vivo activity in animal models of epilepsy and neuropathic pain.
• Water Networks Contribute to Enthalpy/Entropy Compensation in Protein–Ligand Binding
  作者：Benjamin Breiten、Matthew R. Lockett、Woody Sherman、Shuji Fujita、Mohammad Al-Sayah、Heiko Lange、Carleen M. Bowers、Annie Heroux、Goran Krilov、George M. Whitesides

  DOI：10.1021/ja4075776

  日期：2013.10.16

  The mechanism (or mechanisms) of enthalpy-entropy (HIS) compensation in protein ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands-human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination-that we use to define enthalpy/entropy (HIS) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.