1-(2,3-dihydro-1H-inden-5-yl)thiourea | 117174-86-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 1-(2,3-dihydro-1H-inden-5-yl)thiourea
• 英文别名: 2,3-dihydro-1H-inden-5-ylthiourea
• CAS: 117174-86-4
• 化学式: C₁₀H₁₂N₂S
• mdl: MFCD01935531
• 分子量: 192.285
• InChiKey: FFJKDGGVANMBQI-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177 °C(Solv: ethyl acetate (141-78-6); ligroine (8032-32-4))
• 沸点：
  326.5±52.0 °C(Predicted)
• 密度：
  1.311±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  70.1
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(2,3-dihydro-1H-inden-5-yl)thiourea 在 ammonium hydroxide 、 溴 、 溶剂黄146 作用下， 生成 6,7-二氢-5H-茚并[5,6-d][1,3]噻唑-2-胺
  参考文献：
  名称：

  新的1,4-苯并噻嗪衍生物的合成和生物活性。

  摘要：

  合成了新的2H-1,4-苯并噻嗪-3（4H）-在2位具有（4-苯基-1-哌嗪基）烷基部分的衍生物，并测试了其钙拮抗和钙调蛋白拮抗活性。还评估了自发性高血压大鼠的抗高血压作用。通常，这些化合物是相当弱的钙通道阻滞剂，尽管相反，它们中的许多具有中度至强效的钙调蛋白拮抗活性，以及​​2- [3-（4-（4-氟苯基）-1-哌嗪基]丙基]- 2H-1,4-苯并噻嗪-3（4H）-一衍生物45、74和75显示有效的降压作用。

  DOI：

  10.1248/cpb.39.2888
• 作为产物：
  描述：

  5-氨基茚旦 在 ammonium hydroxide 、 三光气 作用下， 以 二氯甲烷 、 氯仿 、 丙酮 为溶剂， 反应 4.17h， 生成 1-(2,3-dihydro-1H-inden-5-yl)thiourea
  参考文献：
  名称：

  Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

  摘要：

  Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.

  DOI：

  10.1021/jm501127s

文献信息

• 4-Pyridylanilinothiazoles That Selectively Target von Hippel−Lindau Deficient Renal Cell Carcinoma Cells by Inducing Autophagic Cell Death
  作者：Michael P. Hay、Sandra Turcotte、Jack U. Flanagan、Muriel Bonnet、Denise A. Chan、Patrick D. Sutphin、Phuong Nguyen、Amato J. Giaccia、William A. Denny

  DOI：10.1021/jm901457w

  日期：2010.1.28

  recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure−activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in

  肾细胞癌 (RCC) 对预后不良的晚期 RCC 的标准治疗无效；因此，晚期 RCC 的治疗代表了未满足的临床需求。von Hippel-Lindau (VHL) 肿瘤抑制基因在大多数 RCC 中发生突变或失活。我们最近发现了一种 4-pyridyl-2-anilinothiazole (PAT)，它对 VHL 缺陷的肾细胞具有选择性的细胞毒性，这种毒性是通过诱导自噬和增加自溶酶体的酸化来介导的。我们报告了围绕此 PAT 导联的构效关系 (SAR) 的探索。使用成对的 RCC4 细胞系合成并在体外测试三个环中每个环上具有取代基的类似物以及环之间的各种接头。描述不同化学特征对效力的相对空间贡献的等高线图说明了一个区域，与吡啶环相邻，具有进一步发展的潜力。探索这个域的例子验证了这种方法，并可能为开发这种新的化学型作为 RCC 治疗的靶向方法提供机会。
• [EN] HETEROARYL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE IN CANCER TREATMENT<br/>[FR] COMPOSÉS HÉTÉROARYLE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2009114552A1

  公开（公告）日：2009-09-17

  Provided herein are novel heteroaryl compounds, compositions comprising the compounds, and methods of treatment or prevention comprising administration of the compounds. The compounds are effective in the targeting of cells defective in the von Hippel-Lindau gene and in inducing autophagic cell death. The methods are directed to treating or preventing diseases such as cancer, and in particular cancers resulting from von Hippel-Lindau disease. The compounds of the invention may be administered in combination with another therapeutic agent.

  本文提供了新颖的杂环芳基化合物，包含这些化合物的组合物，以及包括给予这些化合物的治疗或预防方法。这些化合物在靶向冯·希普尔-林道（von Hippel-Lindau）基因缺陷细胞和诱导自噬性细胞死亡方面具有有效性。这些方法旨在治疗或预防癌症等疾病，特别是由冯·希普尔-林道疾病引起的癌症。本发明的化合物可以与另一种治疗剂联合给药。
• Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas
  作者：C. R. Rasmussen、F. J. Villani, Jr.、L. E. Weaner、B. E. Reynolds、A. R. Hood、L. R. Hecker、S. O. Nortey、A. Hanslin、M. J. Costanzo、E. T. Powell、A. J. Molinari

  DOI：10.1055/s-1988-27605

  日期：——

  An improved procedure for the preparation of arylthioureas consists of the reaction of benzoyl isothiocyanate with anilines in acetone and debenzoylation of the resultant N-aryl-N′-benzoylthioureas with 5% aqueous sodium hydroxide. Bicycloalkylthioureas and N-(arylalkyl)thioureas (e.g., 9H-9-fluorenylthiourea) are directly prepared from the corresponding isothiocyanates and ammonia.

  制备芳基硫脲的改进方法包括将苯甲酰异硫氰酸酯与苯胺在丙酮中反应，然后用5%氢氧化钠水溶液对生成的N-芳基-N'-苯甲酰硫脲进行去苯甲酰化。双环烷基硫脲和N-(芳烷基)硫脲（例如9H-9-芴基硫脲）可直接由相应的异硫氰酸酯与氨反应制备。
• A Versatile Synthesis of Novel<i>N</i>,<i>N</i>,<i>N</i>″-Trisubstituted Guanidines
  作者：C. R. Rasmussen、F. J. Villani, Jr.、B. E. Reynolds、J. N. Plampin、A. R. Hood、L. R. Hecker、S. O. Nortey、A. Hanslin、M. J. Costanzo、R. M. Howse, Jr.、A. J. Molinari

  DOI：10.1055/s-1988-27606

  日期：——

  N,N,N″-Trisubstituted guanidines (most of them N″-aryl-N-azacycloalkanecarboximidamides) are prepared in generally good yields by S-methylation of monosubstituted thioureas with methyl iodide in methanol or acetone and reaction of the resultant methyl carbamimidothioate hydroiodides with secondary amines in boiling tert-butyl alcohol or acetonitrile.

  N,N,N″-三取代胍（大部分是N″-芳基-N-氮杂环烷羧基亚胺）通常以良好的产率通过以下步骤制备：将单取代硫脲与甲基碘在甲醇或丙酮中进行S-甲基化反应，然后将所得的甲基氨基甲亚胺硫醇氢碘酸盐与二级胺在沸腾的叔丁醇或丙酮腈中反应。
• 신규한 디플루오로아세트산 유도체 화합물 및 이를 포함한 조성물
  申请人：Pusan National University Industry-University Cooperation Foundation 부산대학교 산학협력단(220040044843) BRN ▼621-82-06530

  公开号：KR20200011270A

  公开（公告）日：2020-02-03

  본 발명은 신규한 디플루오로아세트산 유도체 화합물 및 이를 포함하는 다양한 용도의 조성물에 관한 것으로, 상기 디플루오로아세트산 유도체 화합물은 PPARα, β 또는 γ 중 어느 하나를 활성화시키는 어고니스트로서 작용할 수 있을 뿐만 아니라, 이중 효능 또는 삼중 효능을 나타낼 수 있는 바, 따라서 PPARs이 관여하는 대사성 질환을 보다 효과적으로 예방, 개선 내지 치료할 수 있고, 더 나아가 미백 및 주름 개선 활성, 항염증 및 항산화 효과까지 나타낼 수 있으므로, 다양한 조성물로서 유용하게 활용될 수 있다.

  本发明涉及一种新型的二氟乙酸衍生物化合物及包含它的各种用途的组合物，所述二氟乙酸衍生物化合物可以作为激活PPARα、β或γ中任一种的激动剂，不仅可以发挥单一作用，还可以表现出双重或三重效应，因此可以更有效地预防、改善或治疗与PPARs相关的代谢性疾病，同时还表现出美白和减少皱纹的活性，具有抗炎和抗氧化效果，因此可以作为各种组合物中有用的成分。