2-(3-氯苯基)-1,3-噻唑-4-甲醛 | 859850-99-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(3-氯苯基)-1,3-噻唑-4-甲醛
• 中文别名: 2-(3-氯苯基)-噻唑-4-甲醛
• 英文名称: 2-(3-chlorophenyl)thiazole-4-carbaldehyde
• 英文别名: 2-(3-chlorophenyl)-1,3-thiazole-4-carbaldehyde
• CAS: 859850-99-0
• 化学式: C₁₀H₆ClNOS
• 分子量: 223.683
• InChiKey: XMXWYXGIKFBCGR-UHFFFAOYSA-N

物化性质

• 熔点：
  103 °C
• 沸点：
  391.0±48.0 °C(Predicted)
• 密度：
  1.388±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934100090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H317,H319

反应信息

• 作为反应物：
  描述：

  罗丹宁 、 2-(3-氯苯基)-1,3-噻唑-4-甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以22%的产率得到(Z)-5-((2-(3-chlorophenyl)thiazol-4-yl)methylene)-2-thioxothiazolidin-4-one
  参考文献：
  名称：

  Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family

  摘要：

  The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and 1(562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC55 of 0.75 mu M against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.02.056
• 作为产物：
  描述：

  3-氯苯腈 在 吡啶 、 manganese(IV) oxide 、 硫酸 、 硫化氢 、 水 、 三乙胺 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 14.0h， 生成 2-(3-氯苯基)-1,3-噻唑-4-甲醛
  参考文献：
  名称：

  多官能化 4-（2-芳基噻唑-4-基）-4H-色烯的合成和体外细胞毒性

  摘要：

  新系列的 4-芳基-4H-色烯在4-位带有2-芳基噻唑-4-基部分被制备为潜在的细胞毒性剂。使用MTT比色法研究合成的4-芳基-4H-色烯与众所周知的抗癌药物依托泊苷的体外细胞毒活性。其中，2-(2-氯苯基)噻唑-4-基类似物4b对鼻咽表皮样癌KB、髓母细胞瘤DAOY和星形细胞瘤1321N1显示出最有效的活性，以及​​带有2-(4-氯苯基)噻唑的化合物4d色烯环4-位的4-基部分对乳腺癌细胞MCF-7、肺癌细胞A549和结肠腺癌细胞SW480表现出最好的抑制活性，IC50值小于5 μM。

  DOI：

  10.1002/ardp.200900198

文献信息

• Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain
  作者：Xue Zhi Zhao、David Hymel、Terrence R. Burke

  DOI：10.1016/j.bmcl.2016.08.098

  日期：2016.10

  potent previously known polo-like kinase 1 (Plk1) polo-box domain (PBD) binding inhibitors. This improved binding may result by accessing a newly identified auxiliary region proximal to a key hydrophobic cryptic pocket on the surface of the protein. Our findings could have general applicability to the design of PBD-binding antagonists.

  通过涉及使用基于肟连接的策略初步筛选一组87个醛的过程，我们能够实现比最有效的先前已知的polo-like激酶1（Plk1）polo-box的亲和力提高数倍。域（PBD）结合抑制剂。这种改善的结合可以通过接近蛋白质表面上关键疏水隐窝的新近识别出的辅助区域来实现。我们的发现可能普遍适用于PBD结合拮抗剂的设计。
• 4-Aryl-4H-Chromene-3-Carbonitrile Derivatives: Evaluation of Src Kinase Inhibitory and Anticancer Activities
  作者：Asal Fallah-Tafti、Rakesh Tiwari、Amir Nasrolahi Shirazi、Tahmineh Akbarzadeh、Deendayal Mandal、Abbas Shafiee、Keykavous Parang、Alireza Foroumadi

  DOI：10.2174/157340611796799258

  日期：2011.9.1

  Src kinase mutations and/or overexpression have been implicated in the development of a number of human cancers including colon, breast, and lung cancers. Thus, designing potent and selective Src kinase inhibitors as anticancer agents is a subject of major interest. A series of 4-aryl substituted derivatives of 2-amino-7-dimethylamino-4H-chromene- 3-carbonitrile were synthesized using one-pot reaction of appropriate substituted aromatic aldehydes, malononitrile, and 3-(dimethylamino)phenol in the presence of piperidine. All 23 compounds were evaluated for inhibition of Src kinase and cell proliferation in human colon adenocarcinoma (HT-29) and leukemia (CCRF-CEM) cell lines. Among the tested compounds, 2-chlorophenyl- (4c), 3-nitrophenyl- (4h), 4-trifluoromethyphenyl- (4i), and 2,3-dichlorophenyl- (4k) substituted chromenes showed Src kinase inhibitory effect with IC50 values of 11.1-18.3 μM. Compound 4c was relatively selective against Src (IC50 = 11.1 μM), when compared with selected kinases, epidermal growth factor receptor (EGFR, IC50 300 μM), C-terminal Src kinase (Csk, IC50 = 101.7 μM), and lymphocyte-specific protein tyrosine kinase (Lck, IC50 = 46.8 μM). 3-Chlorophenyl substituted thiazole (4v) and 2-chlorophenylsubstituted thiazole (4u) chromene derivatives inhibited the cell proliferation of HT-29 and CCRF-CEM by 80% and 50%, respectively, at a concentration of 50 μM. The data indicate that 4H-chromene-3-carbonitrile scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.

  Src 激酶突变和/或过度表达与结肠癌、乳腺癌和肺癌等多种人类癌症的发病有关。因此，设计强效且具有选择性的 Src 激酶抑制剂作为抗癌药物是一个备受关注的课题。在哌啶的存在下，利用适当取代的芳香醛、丙二腈和 3-（二甲基氨基）苯酚的一锅反应，合成了一系列 2-amino-7-dimethylamino-4H-chromene- 3-carbonitrile 的 4-芳基取代衍生物。对所有 23 种化合物在人结肠腺癌（HT-29）和白血病（CCRF-CEM）细胞系中对 Src 激酶和细胞增殖的抑制作用进行了评估。在测试的化合物中，2-氯苯基（4c）、3-硝基苯基（4h）、4-三氟甲基苯基（4i）和 2,3-二氯苯基（4k）取代的色烯类化合物具有抑制 Src 激酶的作用，IC50 值为 11.1-18.3 μM。与选定的激酶、表皮生长因子受体（EGFR，IC50 300 μM）、C-末端 Src 激酶（Csk，IC50 = 101.7 μM）和淋巴细胞特异性蛋白酪氨酸激酶（Lck，IC50 = 46.8 μM）相比，化合物 4c 对 Src 具有相对的选择性（IC50 = 11.1 μM）。3-氯苯基取代的噻唑（4v）和 2-氯苯基取代的噻唑（4u）色烯衍生物在 50 μM 浓度下分别抑制 HT-29 和 CCRF-CEM 细胞增殖 80% 和 50%。这些数据表明，4H-色烯-3-甲腈支架具有进一步优化的潜力，可用于设计更有效的 Src 激酶抑制剂和/或抗癌先导化合物。