3,3-Diphenyl-propyl-isothiocyanat | 32265-78-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,3-Diphenyl-propyl-isothiocyanat
• 英文别名: 3,3-Diphenylpropylisothiocyanate；(3-isothiocyanato-1-phenylpropyl)benzene
• CAS: 32265-78-4
• 化学式: C₁₆H₁₅NS
• 分子量: 253.368
• InChiKey: GJBSEMINGSKFNL-UHFFFAOYSA-N

物化性质

• 沸点：
  389.6±31.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,3-Diphenyl-propyl-isothiocyanat 、 di-tert-butyl butane-1,4-diylbis((3-aminopropyl)carbamate) 以 二氯甲烷 为溶剂， 以89%的产率得到1,12-bis-{3-[1-(3,3-diphenylpropyl)thioureado]}-4,9-[N-(tert-butyl)oxycarbonyl]-4,9-diazadodecane
  参考文献：
  名称：

  (Bis)urea and (Bis)thiourea Inhibitors of Lysine-Specific Demethylase 1 as Epigenetic Modulators

  摘要：

  The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of isosteric ureas and thioureas that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2 and.transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.

  DOI：

  10.1021/jm100217a
• 作为产物：
  描述：

  triethylamine (3,3-diphenylpropyl)carbamodithioate 在 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 3,3-Diphenyl-propyl-isothiocyanat
  参考文献：
  名称：

  [EN] (BIS) UREA AND (BIS) THIOUREA COMPOUNDS AS EPIGENIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS
  [FR] COMPOSÉS (BIS)URÉE ET (BIS)THIOURÉE EN TANT QUE MODULATEURS ÉPIGÉNIQUES DE LA DÉMÉTHYLASE 1 SPÉCIFIQUE À LA LYSINE ET MÉTHODES DE TRAITEMENT DE TROUBLES

  摘要：

  公开号：

  WO2011022489A3

文献信息

• Discovery of Novel Alkylated (bis)Urea and (bis)Thiourea Polyamine Analogues with Potent Antimalarial Activities
  作者：Bianca K. Verlinden、Jandeli Niemand、Janette Snyman、Shiv K. Sharma、Ross J. Beattie、Patrick M. Woster、Lyn-Marie Birkholtz

  DOI：10.1021/jm200463z

  日期：2011.10.13

  A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3 μM, with the majority having effective IC50 values in the 100–650 nM range. Analogues arrested parasitic

  合成了一系列烷基化（双）脲和（双）硫脲多胺类似物，并在体外筛选了对氯喹敏感和耐药株恶性疟原虫的抗疟活性。所有类似物在小于 3 μM 时均显示出对恶性疟原虫的生长抑制活性，其中大多数具有100–650 nM 范围内的有效 IC 50值。由于核分裂和无性发育的阻滞，类似物在暴露后 24 小时内阻止了寄生生长。此外，这种作用似乎对疟原虫具有细胞毒性和高度选择性（对恶性疟原虫的IC 50低 7000 倍以上）) 并且通过多胺的外源加成是不可逆的。随着含有 3-7-3 或 3-6-3 个碳骨架和取代的末端脲或硫脲部分的多胺类似物的强效抗疟活性的首次报道，我们提出这些化合物代表了一类结构新颖的抗疟药。
• (BIS)UREA AND (BIS)THIOREA COMPOUNDS AS EIPGENIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS
  申请人：Casero Robert A.

  公开号：US20120322877A1

  公开（公告）日：2012-12-20

  The invention provides for novel (bis)urea and (bis)thiourea compounds which are inhibitors of lysine-specific demethylase 1 (LSD1). Such compounds may be used to treat disorders, including cancer.

  该发明提供了一种新型的(双)脲和(双)硫脲化合物，它们是赖氨酸特异性去甲基化酶1 (LSD1)的抑制剂。这些化合物可用于治疗包括癌症在内的多种疾病。
• WO2008/6625
  申请人：——

  公开号：——

  公开（公告）日：——
• Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites
  作者：Bianca K. Verlinden、Marna de Beer、Boobalan Pachaiyappan、Ethan Besaans、Warren A. Andayi、Janette Reader、Jandeli Niemand、Riette van Biljon、Kiplin Guy、Timothy Egan、Patrick M. Woster、Lyn-Marie Birkholtz

  DOI：10.1016/j.bmc.2015.01.036

  日期：2015.8

  A new series of potent potent aryl/alkylated (bis)urea- and (bis) thiourea polyamine analogues were synthesized and evaluated in vitro for their antiplasmodial activity. Altering the carbon backbone and terminal substituents increased the potency of analogues in the compound library 3-fold, with the most active compounds, 15 and 16, showing half-maximal inhibitory concentrations (IC50 values) of 28 and 30 nM, respectively, against various Plasmodium falciparum parasite strains without any cross-resistance. In vitro evaluation of the cytotoxicity of these analogues revealed marked selectivity towards targeting malaria parasites compared to mammalian HepG2 cells (>5000-fold lower IC50 against the parasite). Preliminary biological evaluation of the polyamine analogue antiplasmodial phenotype revealed that (bis) urea compounds target parasite asexual proliferation, whereas (bis) thiourea compounds of the same series have the unique ability to block transmissible gametocyte forms of the parasite, indicating pluripharmacology against proliferative and non-proliferative forms of the parasite. In this manuscript, we describe these results and postulate a refined structure-activity relationship (SAR) model for antiplasmodial polyamine analogues. The terminally aryl/alkylated (bis) urea-and (bis) thiourea-polyamine analogues featuring a 3-5-3 or 3-6-3 carbon backbone represent a structurally novel and distinct class of potential antiplasmodials with activities in the low nanomolar range, and high selectivity against various lifecycle forms of P. falciparum parasites. (C) 2015 Elsevier Ltd. All rights reserved.
• (BIS) UREA AND (BIS) THIOUREA COMPOUNDS AS EPIGENIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS
  申请人：The Johns Hopkins University

  公开号：EP2467359A2

  公开（公告）日：2012-06-27