[(2-Tert-butylcyclohexylidene)amino]thiourea | 452298-78-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(2-Tert-butylcyclohexylidene)amino]thiourea
• CAS: 452298-78-1
• 化学式: C₁₁H₂₁N₃S
• 分子量: 227.374
• InChiKey: HBLUEMIUZULTIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(2-Tert-butylcyclohexylidene)amino]thiourea 在 sodium acetate 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 3-benzyl-2-(2-(2-tert-butylcyclohexylidene)hydrazono)thiazolidin-4-one
  参考文献：
  名称：

  1,3-噻唑烷丁-4-酮衍生物的合成，生物学评估和定量构效关系。具有高抗真菌效力和低细胞毒性的有前途的化学支架

  摘要：

  参考有关噻唑烷酮支架各种生物学特性的最新研究报告，我们合成了一百多种化合物，这些化合物的特征是1,2噻唑烷酮-4-酮核在C2处衍生化，并带有与（环）脂族连接的肼桥。或杂（芳基）部分，以及它们的N-苄基衍生物。这些分子被作为潜在的抗念珠菌药物进行了分析，显示它们具有与成熟的局部和全身性抗真菌药物（即克霉唑，氟康唑，酮康唑，咪康唑，噻康唑，两性霉素B）相当的生物活性，在某些情况下具有更高的生物学活性。具有最低MIC的化合物进行了进一步测试，以评估其细胞毒性作用（CC 50）在Hep2细胞上，证明了其相对安全性。最后，使用QSAR和3-D QSAR模型预测1,3-噻唑烷丁-4-酮支架的假定化学修饰，以设计针对念珠菌的新的和潜在的更具活性的化合物。

  DOI：

  10.1016/j.ejmech.2017.09.026
• 作为产物：
  描述：

  2-叔-丁基环己酮 、 氨基硫脲 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 [(2-Tert-butylcyclohexylidene)amino]thiourea
  参考文献：
  名称：

  1,3-噻唑烷丁-4-酮衍生物的合成，生物学评估和定量构效关系。具有高抗真菌效力和低细胞毒性的有前途的化学支架

  摘要：

  参考有关噻唑烷酮支架各种生物学特性的最新研究报告，我们合成了一百多种化合物，这些化合物的特征是1,2噻唑烷酮-4-酮核在C2处衍生化，并带有与（环）脂族连接的肼桥。或杂（芳基）部分，以及它们的N-苄基衍生物。这些分子被作为潜在的抗念珠菌药物进行了分析，显示它们具有与成熟的局部和全身性抗真菌药物（即克霉唑，氟康唑，酮康唑，咪康唑，噻康唑，两性霉素B）相当的生物活性，在某些情况下具有更高的生物学活性。具有最低MIC的化合物进行了进一步测试，以评估其细胞毒性作用（CC 50）在Hep2细胞上，证明了其相对安全性。最后，使用QSAR和3-D QSAR模型预测1,3-噻唑烷丁-4-酮支架的假定化学修饰，以设计针对念珠菌的新的和潜在的更具活性的化合物。

  DOI：

  10.1016/j.ejmech.2017.09.026

文献信息

• Elucidation of the mechanisms governing the thermal diastereomerization of bioactive chiral 1,3,4-thiadiazoline spiro-cyclohexyl derivatives towards their anancomeric stereoisomers
  作者：S. Menta、S. Carradori、G. Siani、D. Secci、L. Mannina、A. P. Sobolev、R. Cirilli、M. Pierini

  DOI：10.1039/c6ra13727j

  日期：——

  The kinetics of the thermal isomerization of some diastereomers of three chiral 1,3,4 thiadiazoline derivatives, selected as case studies of structures resulting from mono-alkyl substitution of the anancomeric 4-acetyl-2-acetamido-1,3,4-thiadiazolinyl-spiro-cyclohexane (TsC) framework, have been investigated in order to elucidate the possible mechanistic pathways and the structural factors responsible

  三种手性1,3,4噻二唑啉衍生物的一些非对映异构体的热异构动力学，被选作结构学研究的实例，该结构是由对乙酰基4-乙酰基-2-乙酰酰胺基-1,3,4-噻二唑啉基的单烷基取代产生的-螺-环己烷（TsC）框架，已进行了研究，以阐明可能的机制途径和负责所观察到的螺结稳定性的结构因素。插入甲基或t相对于螺连接的C 2或C 3位置上的丁基产生两个立体中心，因此存在两对对映异构体。通过分批动力学测定，已经在不同的溶剂和不同的温度下测量了不稳定度较低的对映异构体异构化为最稳定的对映体的一级速率常数。通过DFT计算和线性溶剂化能量关系（LSER）分析，已成功地对获得的数据进行了合理化。所获得的阐明应使得有可能计划更合理地合成这种药理活性化合物，从而提供一种实用的工具，可用于控制所涉及的立体化学和螺连接的不稳定性。
• Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii
  作者：Melissa D'Ascenzio、Bruna Bizzarri、Celeste De Monte、Simone Carradori、Adriana Bolasco、Daniela Secci、Daniela Rivanera、Nathan Faulhaber、Claudia Bordón、Lorraine Jones-Brando

  DOI：10.1016/j.ejmech.2014.08.046

  日期：2014.10

  We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition. (c) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and pharmacological screening of a large library of 1,3,4-thiadiazolines as innovative therapeutic tools for the treatment of prostate cancer and melanoma
  作者：Celeste De Monte、Simone Carradori、Daniela Secci、Melissa D'Ascenzio、Paolo Guglielmi、Adriano Mollica、Stefania Morrone、Susanna Scarpa、Anna Maria Aglianò、Sabrina Giantulli、Ida Silvestri

  DOI：10.1016/j.ejmech.2015.10.023

  日期：2015.11

  Antimitotic agents are widely used in cancer chemotherapy but the numerous side effects and the onset of resistance limit their clinical efficacy. Therefore, with the purpose of discovering more selective and efficient anticancer agents to be administered alone or in combination with traditional drugs, we synthesized a large library of 1,3,4-thiadiazoline analogues, maintaining the pharmacophoric structure of an antiproliferative compound known as K858: this is a new inhibitor of kinesin Eg5, able to induce the mitotic arrest in colorectal cancer cells and in xenograft ovarian cancer cells. We screened 103 compounds to assess their antiproliferative activity on PC3 prostate cancer cell line. Two derivatives, compounds 32 (corresponding to K858) and 33, have shown to be the most effective against prostate tumor cells and also towards two melanoma cell lines (SK-MEL-5 and SK-MEL-28) at low micromolar concentrations, confirming the pharmacological activity of this scaffold and revealing the potential role of 1,3,4-thiadiazolines in the management of cancer. (C) 2015 Elsevier Masson SAS. All rights reserved.
• The Anancomeric Character of the Pharmacophore 1,3,4-Thiadiazoline Framework in Chiral Spiro-Cyclohexyl Derivatives: Effects on Stereochemistry and Spiro-Junction Lability. Thermodynamic Aspects
  作者：Sergio Menta、Simone Carradori、Daniela Secci、Cristina Faggi、Luisa Mannina、Roberto Cirilli、Marco Pierini

  DOI：10.1021/acs.joc.5b01635

  日期：2015.12.18

  Three new and easily accessible chiral compounds, containing the pharmacophore 1,3,4-thiadiazoline nucleus joined by a spiro center to a monoalkyl (methyl or t-butyl) substituted cyclohexyl fragment, have been synthesized and fully characterized from the Structural and stereochemical point Of view. The formation of a spiro-cyclohexyl-thiadiazoline system (sCT) offered the rare opportunity to generate at room temperature both anancomeric structures, displaying alkyl groups bound to the cydohexyl ring in equatorial position; and other quite stable stereoisomers in which the same alkyl moieties are, instead, inserted in axial position, even for the extreme case represented by the really bulky t-butyl group. DFT calculations led to a clear rationalization of such stereochemical behaviors, pointing out that in all cases they arise from the unexpected strong anancomeric character possessed by the sCT framework in its 4-acetyl substituted version. In consideration of the large number of substances in which the 1,3,4-thiadiatoline heterocycle has been found as the active pharmacophore, the results discussed in thiS work may provide solid bases to allow a rational design of new chiral bioactive spiro-thiadiazolines characterized by well-defined stereochemical structures and single anancomeric geometries.