6-(4-chlorophenyl)-2-methylimidazo[2,1-b]thiazole-5-carbaldehyde | 123772-37-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-(4-chlorophenyl)-2-methylimidazo[2,1-b]thiazole-5-carbaldehyde
• 英文别名: 6-(4-Chlorophenyl)-2-methylimidazo[2,1-B][1,3]thiazole-5-carbaldehyde
• CAS: 123772-37-2
• 化学式: C₁₃H₉ClN₂OS
• 分子量: 276.746
• InChiKey: CKEKNWYPPSGWTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-chlorophenyl)-2-methylimidazo[2,1-b]thiazole-5-carbaldehyde 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 2-Methyl-6-p-chlorophenylimidazo<2,1-b>thiazol-5-ylmethyl m-Trifluoromethylphenylcarbamate
  参考文献：
  名称：

  Andreani, Aldo; Rambaldi, Mirella; Carloni, Patricia, Journal of Heterocyclic Chemistry, 1989, vol. 26, p. 525 - 529

  摘要：

  DOI：
• 作为产物：
  描述：

  6-(4-chlorophenyl)-2-methylimidazo[2,1-b]thiazole 、 N,N-二甲基甲酰胺 在 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 6.0h， 以67%的产率得到6-(4-chlorophenyl)-2-methylimidazo[2,1-b]thiazole-5-carbaldehyde
  参考文献：
  名称：

  Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies

  摘要：

  The DNA alkylating prodrug cyclophosphamide (CPA), alone or in combination with other agents, is one of the most commonly used anti-cancer agents. As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Therefore, hCAR agonists represent novel sensitizers for CPA-based therapies. Among known hCAR agonists, compound 6-(4-chlorophenyl)imidazo-[2,1-b]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) is the most potent and broadly utilized in biological studies. Through structural modification of CITCO, we have developed a novel compound DL5016 (32), which has an EC50 value of 0.66 mu M and E-MAX value of 4.9 when activating hCAR. DL5016 robustly induced the expression of hCAR target gene CYP2B6, at both the mRNA and protein levels, and caused translocation of hCAR from the cytoplasm to the nucleus in human primary hepatocytes. The effects of DL5016 were highlighted by dramatically enhancing the efficacy of CPA-based cytotoxicity to non-Hodgkin lymphoma cells. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.031

文献信息

• Potential Antitumor Agents. 24. Synthesis and Pharmacological Behavior of Imidazo[2,1-<i>b</i>]thiazole Guanylhydrazones Bearing at Least One Chlorine
  作者：Aldo Andreani、Mirella Rambaldi、Alberto Leoni、Alessandra Locatelli、Rosaria Bossa、Alessandra Fraccari、Iraklis Galatulas、Gaetano Salvatore

  DOI：10.1021/jm9509307

  日期：1996.1.1

  research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other

  结合先前有关咪唑并[2,1-b]-噻唑胍酰肼的抗肿瘤活性的研究，本文报道了合成的新衍生物的合成，这些衍生物经测试具有抗肿瘤和正性肌力活性。在大多数情况下，体外实验（HeLa）的细胞毒性数据与体内抗肿瘤数据（Ehrlich）一致。活性化合物在6位带有苯环。另一方面，最活跃的强心剂没有苯环。
• Dihydropyridines bearing an imidazo[2,1-b]thiazole system
  作者：A Andreani、A Leoni、M Rambaldi、A Locatelli、R Bossa、I Galatulas、M Chiericozzi、M Bissoli

  DOI：10.1016/s0223-5234(97)87542-3

  日期：1997.1

  This paper reports the synthesis of imidazo[2,1-b]thiazoles, bearing a dihydropyridine ring at the 5 or 6 position, which were tested for antiarrhythmic, inotropic and chronotropic activities. Nine of the ten compounds bearing double bond at the 2,3 position and the same dihydropyridine as nifedipine at the 5 position, were antiarrhythmic; moreover one of them (bearing a methyl group at the 2 position) was devoid of negative inotropic activity.
• Substituted 3-(5-Imidazo[2,1-<i>b</i>]thiazolylmethylene)-2-indolinones and Analogues: Synthesis, Cytotoxic Activity, and Study of the Mechanism of Action
  作者：Aldo Andreani、Massimiliano Granaiola、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Lucilla Varoli、Natalia Calonghi、Concettina Cappadone、Giovanna Farruggia、Claudio Stefanelli、Lanfranco Masotti、Tam L. Nguyen、Ernest Hamel、Robert H. Shoemaker

  DOI：10.1021/jm2012694

  日期：2012.3.8

  The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.
• Antitumor Activity of New Substituted 3-(5-Imidazo[2,1-<i>b</i>]thiazolylmethylene)-2-indolinones and 3-(5-Imidazo[2,1-<i>b</i>]thiadiazolylmethylene)-2-indolinones: Selectivity against Colon Tumor Cells and Effect on Cell Cycle-Related Events
  作者：Aldo Andreani、Silvia Burnelli、Massimiliano Granaiola、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Lucilla Varoli、Natalia Calonghi、Concettina Cappadone、Manuela Voltattorni、Maddalena Zini、Claudio Stefanelli、Lanfranco Masotti、Robert H. Shoemaker

  DOI：10.1021/jm800827q

  日期：2008.12.11

  The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
• CAR ACTIVATOR AGENTS FOR CYCLOPHOSPHAMIDE-BASED TREATMENTS OF CANCER
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE

  公开号：US20200352915A1

  公开（公告）日：2020-11-12

  The invention relates to selective small molecule human constitutive androstane receptor (hCAR) activators of Formula (I) or (II), pharmaceutical compositions thereof, and use thereof for the treatment of hematologic malignancies and other cancers. The small molecule hCAR activator in combination with CPA based chemotherapy regimen provides a synergistic effect to help promote cytoxicity of the cyclophosphamide (CPA) based anticancer treatments including CHOP regimen (CPA, doxorubicin, vincristine, and prednisone) by preferential induction of CYP2B6 over CYP3A4 and promoting the formation of therapeutically active CPA metabolite 4-OH-CPA.