5-(1-naphthalenylmethyl)-2-thiazolamine | 207463-35-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(1-naphthalenylmethyl)-2-thiazolamine
• 英文别名: 5-(1-naphthylmethyl)thiazol-2-amine；5-(Naphthalen-1-ylmethyl)-1,3-thiazol-2-amine
• CAS: 207463-35-2
• 化学式: C₁₄H₁₂N₂S
• mdl: MFCD00547830
• 分子量: 240.329
• InChiKey: WKKWSBMLQGKXKT-UHFFFAOYSA-N

物化性质

• 熔点：
  180-181 °C(Solv: carbon tetrachloride (56-23-5))
• 沸点：
  448.2±14.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(1-naphthalenylmethyl)-2-thiazolamine 在 sodium carbonate 、 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 4.25h， 生成 2-(2-aminophenyl)sulfanyl-N-[5-(1-naphthylmethyl)thiazol-2-yl]acetamide
  参考文献：
  名称：

  氨基噻唑类作为有效和选择性Sirt2抑制剂的结构-活性关系研究

  摘要：

  Sirtuins是NAD +-依赖性蛋白脱酰基酶，其从组蛋白和其他底物蛋白中的赖氨酸的ε-氨基上裂解掉乙酰基以及其他酰基。人类Sirt2（hSirt2）活性的失调与癌症，炎症和神经退行性病变的发病机制有关，这使得对hSirt2活性的调节成为药物干预的有前途的策略。sirtuin重排配体（SirReals）最近已被我们发现为高效且同型选择性的hSirt2抑制剂。在这里，我们提出了一个定义明确的结构-活性关系研究，该研究合理化了SirReals的独特功能，并探讨了该支架在抑制剂效能方面的修饰极限。而且，我们提出了具有优化的SirReal衍生物的hSirt2晶体结构，该衍生物具有改善的体外活性。最后，我们显示了由我们改良的前导结构导致的hSirt2靶向微管蛋白的细胞过度乙酰化。

  DOI：

  10.1021/acs.jmedchem.5b01517
• 作为产物：
  描述：

  1-naphthyldiazonium chloride 在 盐酸 、 iron(III) chloride hexahydrate 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 5-(1-naphthalenylmethyl)-2-thiazolamine
  参考文献：
  名称：

  氨基噻唑类作为有效和选择性Sirt2抑制剂的结构-活性关系研究

  摘要：

  Sirtuins是NAD +-依赖性蛋白脱酰基酶，其从组蛋白和其他底物蛋白中的赖氨酸的ε-氨基上裂解掉乙酰基以及其他酰基。人类Sirt2（hSirt2）活性的失调与癌症，炎症和神经退行性病变的发病机制有关，这使得对hSirt2活性的调节成为药物干预的有前途的策略。sirtuin重排配体（SirReals）最近已被我们发现为高效且同型选择性的hSirt2抑制剂。在这里，我们提出了一个定义明确的结构-活性关系研究，该研究合理化了SirReals的独特功能，并探讨了该支架在抑制剂效能方面的修饰极限。而且，我们提出了具有优化的SirReal衍生物的hSirt2晶体结构，该衍生物具有改善的体外活性。最后，我们显示了由我们改良的前导结构导致的hSirt2靶向微管蛋白的细胞过度乙酰化。

  DOI：

  10.1021/acs.jmedchem.5b01517

文献信息

• Synthesis and biological evaluation of aminothiazoles against Histoplasma capsulatum and Cryptococcus neoformans
  作者：Keisuke Ishita、Stavros Stefanopoulos、Ahmed Khalil、Xiaolin Cheng、Werner Tjarks、Chad A. Rappleye

  DOI：10.1016/j.bmc.2018.01.024

  日期：2018.5

  group, the thiazole core, and the methylene linker between these two structural elements. In general, compounds with lipophilic [5+6] bicyclic ring systems, such as the 7-benzothiophenyl- and 4-indanyl groups, at the 5-position were 2–3 times more active against both fungal species as compared to 41F5. Also, introduction of a carbonyl group at the methylene linker of 41F5 resulted in a 2–3-fold increase

  描述了四十种新型 2-氨基唑类似物库的设计和合成，以及它们作为抗荚膜组织胞浆菌和新型隐球菌的抗真菌化合物的评估。这些结构源自N -[5-(1-萘基甲基)-2-噻唑基]环己烷甲酰胺 (41F5)，这是一种先前通过表型筛选鉴定的抑真菌剂（ Antimicrob Agents Chemother. 2013；57:4349）。提高 41F5 效力和水溶性的修饰主要集中在 5-萘基、噻唑核心以及这两个结构元件之间的亚甲基连接基。一般来说，5 位具有亲脂性 [5+6] 双环系统（例如 7-苯并噻吩基和 4-茚满基）的化合物对两种真菌的活性比 41F5 高 2-3 倍。此外，在 41F5 的亚甲基连接基上引入羰基导致效力增加 2-3 倍。这些高活性化合物还对鼠 P388D1 巨噬细胞表现出较低的毒性，导致选择性指数范围为 63 至 >200。对氟康唑敏感的新型隐球菌菌株具有高度活性的化合物对这种真菌的氟康唑抗性变种具有几乎相同的活性，表明
• Obushak; Matiichuk; Ganushchak, Russian Journal of Organic Chemistry, 1997, vol. 33, # 7, p. 1010 - 1013
  作者：Obushak、Matiichuk、Ganushchak

  DOI：——

  日期：——
• Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans
  作者：Ahmed Khalil、Jessica A. Edwards、Chad A. Rappleye、Werner Tjarks

  DOI：10.1016/j.bmc.2014.12.006

  日期：2015.2

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.
• Non-Peptidic Inhibitors of AKAP/PKA Interaction
  申请人：Klussmann Enno

  公开号：US20090176773A1

  公开（公告）日：2009-07-09

  The invention relates to non-peptidic molecules which modulate, especially inhibit, the interaction of protein kinase A (PKA) and A kinase anchor proteins (AKAP) and to a host or target organism that comprises said non-peptidic compounds or recognition molecules directed to said compounds, such as e.g. antibodies or chelating agents. The invention also relates to a pharmaceutical agent, especially for use in the treatment of diseases that are associated with a disturbance of the cAMP signal path, especially insipid diabetes, hypertonia, pancreatic diabetes, duodenal ulcer, asthma, heart failure, obesity, AIDS, edema, hepatic cirrhosis, schizophrenia and others. The invention also relates to the use of the inventive molecules.
• Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study
  作者：Matthias Schiedel、Tobias Rumpf、Berin Karaman、Attila Lehotzky、Judit Oláh、Stefan Gerhardt、Judit Ovádi、Wolfgang Sippl、Oliver Einsle、Manfred Jung

  DOI：10.1021/acs.jmedchem.5b01517

  日期：2016.2.25

  Here, we present a well-defined structure–activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the

  Sirtuins是NAD +-依赖性蛋白脱酰基酶，其从组蛋白和其他底物蛋白中的赖氨酸的ε-氨基上裂解掉乙酰基以及其他酰基。人类Sirt2（hSirt2）活性的失调与癌症，炎症和神经退行性病变的发病机制有关，这使得对hSirt2活性的调节成为药物干预的有前途的策略。sirtuin重排配体（SirReals）最近已被我们发现为高效且同型选择性的hSirt2抑制剂。在这里，我们提出了一个定义明确的结构-活性关系研究，该研究合理化了SirReals的独特功能，并探讨了该支架在抑制剂效能方面的修饰极限。而且，我们提出了具有优化的SirReal衍生物的hSirt2晶体结构，该衍生物具有改善的体外活性。最后，我们显示了由我们改良的前导结构导致的hSirt2靶向微管蛋白的细胞过度乙酰化。