6-(2,5-dimethoxyphenyl)imidazo[2,1-b]thiazole-5-carboxaldehyde | 143951-29-5

• 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-(2,5-dimethoxyphenyl)imidazo[2,1-b]thiazole-5-carboxaldehyde
• 英文别名: 6-(2,5-Dimethoxyphenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde
• CAS: 143951-29-5
• 化学式: C₁₄H₁₂N₂O₃S
• 分子量: 288.327
• InChiKey: KCCKYYCMPUBMGV-UHFFFAOYSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  81.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(2,5-dimethoxyphenyl)imidazo[2,1-b]thiazole-5-carboxaldehyde 在 sodium dithionite 、 ammonium cerium(IV) nitrate 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 2.0h， 生成 6-(2,5-Dihydroxyphenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde
  参考文献：
  名称：

  潜在的抗肿瘤药。37.由咪唑并[2，1-b]噻唑和新的杂环系统噻唑并[2′，3′：2，3]咪唑并[4，5-c]喹啉合成胍基hydr并具有抗肿瘤活性。

  摘要：

  本文报道了由咪唑并[2,1-b]噻唑和杂环新体系噻唑并[2'，3'：2,3]咪唑并[4,5-c]喹啉合成的新胍hydr及其抗肿瘤活性。这些化合物已在美国国家癌症研究所测试为潜在的抗肿瘤药物。研究了2-氯-6-（2,5-二甲氧基-4-硝基苯基）咪唑并[2,1-b]噻唑-5-甲醛的胍hydr的作用（41），发现其是抑制剂线粒体呼吸链复合物III的合成，能够诱导细胞株HT29和HL60凋亡。

  DOI：

  10.1021/jm040888s
• 作为产物：
  描述：

  6-(2,5-Dimethoxyphenyl)imidazo[2,1-b][1,3]thiazole 、 N,N-二甲基甲酰胺 在 吡啶 、 三氯氧磷 作用下， 以 氯仿 为溶剂， 生成 6-(2,5-dimethoxyphenyl)imidazo[2,1-b]thiazole-5-carboxaldehyde
  参考文献：
  名称：

  Synthesis and cardiotonic activity of 2,5-dimethyoxyphenylimidazo[2,1-b]thiazoles

  摘要：

  DOI：

  10.1016/0223-5234(92)90159-x

文献信息

• Cystic Fibrosis: A New Target for 4-Imidazo[2,1-<i>b</i>]thiazole-1,4-dihydropyridines
  作者：Roberta Budriesi、Pierfranco Ioan、Alberto Leoni、Nicoletta Pedemonte、Alessandra Locatelli、Matteo Micucci、Alberto Chiarini、Luis J. V. Galietta

  DOI：10.1021/jm200199r

  日期：2011.6.9

  The pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel has attracted significant interest in recent years with the aim to search for rational new therapies for diseases caused by CFTR malfunction. Mutations that abolish the function of CFTR cause the life-threatening genetic disease cystic fibrosis (CF). The most common cause of CF is the deletion of phenylalanine 508 (Delta F508) in the CFTR chloride channel. Felodipine, nifedipine, and other antihypertensive 1,4-dihydropyridines (1,4-DHPs) that block L-type Ca2+ channels are also effective potentiators of CFTR gating, able to correct the defective activity of Delta F508 and other CFTR mutants (Mol. Pharmacol. 2005, 68, 1736). For this purpose, we evaluated the ability of the previously and newly synthesized 4-imidazo[2,1-b]thiazoles-1,4-dihydropyridines without vascular activity and inotropic and/or chronotropic cardiac effects (J. Med. Chem. 2008, 51, 1592) to enhance the activity of Delta F508-CFTR. Our studies indicate compounds 17, 18, 20, 21, 38, and 39 as 1,4-DHPs with an interesting profile of activity.
• 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.
• Imidazo[2,1-<i>b</i>]thiazole System: A Scaffold Endowing Dihydropyridines with Selective Cardiodepressant Activity
  作者：Roberta Budriesi、Pierfranco Ioan、Alessandra Locatelli、Sandro Cosconati、Alberto Leoni、Maria P. Ugenti、Aldo Andreani、Rosanna Di Toro、Andrea Bedini、Santi Spampinato、Luciana Marinelli、Ettore Novellino、Alberto Chiarini

  DOI：10.1021/jm070681+

  日期：2008.3.1

  The synthesis, characterization, and functional in vitro assays in cardiac tissues and smooth muscle (vascular and nonvascular) of a number of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. The binding properties for the novel compounds have been investigated and the interaction with the binding site common to other aryl-dihydropyridines has been demonstrated. Interestingly, the novel 4-aryl-dihydropyridines are L-type calcium channel blockers with a peculiar pharmacological behavior. Indeed, the imidazo[2,1-b]thiazole system is found to confer to the dihydropyridine scaffold an inotropic and/or chronotropic cardiovascular activity with a high selectivity toward the nonvascular tissue. Finally, molecular modeling studies were undertaken for the most representative compounds with the aim of describing the binding properties of the new ligands at molecular level and to rationalize the found structure-activity relationship data. Due to the observed pharmacological behavior of our compounds, they might be promising agents for the treatment of specific cardiovascular pathologies such as cardiac hypertrophy and ischemia.
• Ligand Based Approach to L-Type Calcium Channel by Imidazo[2,1-<i>b</i>]thiazole-1,4-Dihydropyridines: from Heart Activity to Brain Affinity
  作者：Alessandra Locatelli、Sandro Cosconati、Matteo Micucci、Alberto Leoni、Luciana Marinelli、Andrea Bedini、Pierfranco Ioan、Santi Mario Spampinato、Ettore Novellino、Alberto Chiarini、Roberta Budriesi

  DOI：10.1021/jm301839q

  日期：2013.5.23

  The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. To define the calcium blocker nature of the imidazo[2,1-b]thiazole-1,4-DHPs and their selectivity on Ca(v)1.2 and Ca(v)1.3 isoforms, we performed binding studies on guinea pig atrial and ventricular membranes on intact cells expressing the cloned Ca(v)1.2a subunit and on rat brain cortex. To get major insights into the reasons for the affinity for Ca(v)1.2 and/or Ca(v)1.3, molecular modeling studies were also undertaken. Some physicochemical and pharmacokinetic properties of selected compounds were calculated and compared. All the biological data collected and reported herein allowed us to rationalize the structure-activity relationship of the 4-imidazo[2,1-b]thiazole-1,4-DHPs and to identify which of these enhanced the activity at the central level.
• Synthesis and potential coanthracyclinic activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones
  作者：A Andreani、A Locatelli、A Leoni、M Rambaldi、R Morigi、R Bossa、M Chiericozzi、A Fraccari、I Galatulas

  DOI：10.1016/s0223-5234(97)82778-x

  日期：1997.11

  A compound endowed with coanthracyclinic activity should potentiate the antitumor activity of anthracyclines report the synthesis and configuration of a series of substituted while counteracting their cardiodepressant effect. We now the 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones which were tested for both cardiotonic and cytotoxic activity. Several compounds were potent cytotoxic agents and two of them (in particular 3-[6-(2,5-dimethoxyphenyl)-5-imidazo[2,1-b]thiazolylmethylene]-2-indolinone), which showed even cardiotonic activity, are potential coanthracyclinic agents.