2-chloro-6-methylimidazo[2,1-b]thiazole-5-carboxaldehyde | 851076-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并噻唑类
• 英文名称: 2-chloro-6-methylimidazo[2,1-b]thiazole-5-carboxaldehyde
• 英文别名: 2-Chloro-6-methylimidazo[2,1-b][1,3]thiazole-5-carbaldehyde；2-chloro-6-methylimidazo[2,1-b][1,3]thiazole-5-carbaldehyde
• CAS: 851076-74-9
• 化学式: C₇H₅ClN₂OS
• 分子量: 200.649
• InChiKey: LZBKZZBBWCVFFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 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：

  2-chloro-6-methylimidazo[2,1-b]thiazole-5-carboxaldehyde 在 sodium tetrahydroborate 、 三氟化硼乙醚 、 silver(l) oxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 为溶剂， 反应 17.0h， 生成 2-(2-Chloro-6-methyl-imidazo[2,1-b]thiazol-5-ylmethyl)-5,6-dimethoxy-3-methyl-[1,4]benzoquinone
  参考文献：
  名称：

  Effects of new ubiquinone-imidazo[2,1-b]thiazoles on mitochondrial complex I (NADH-ubiquinone reductase) and on mitochondrial permeability transition pore

  摘要：

  In this work we describe the synthesis of a series of imidazo[2,1-b]thiazoles and 2,3-dihydroimidazo[2,1-b]thiazoles connected by means of a methylene bridge to CoQ(0). These compounds were tested as specific inhibitors of the NADH:ubiquinone reductase activity in mitochondrial membranes. The imidazothiazole system when bound to the quinone ring in place of the isoprenoid lateral side chain, may increase the inhibitory effect (with an IC50 for NADH-Q(1) activity ranging between 0.25 and 0.96 muM) whereas the benzoquinone moiety seems to lose the capability to accept electrons from complex I as indicated by very low maximal velocity elicited by the compounds tested. Moreover the low rotenone sensitivity for almost all of these compounds suggests that they are only partially able to interact with the physiological ubiquinone-reduction site. The compounds were investigated for the capability of increasing the permeability transition of the inner mitochondrial membrane in isolated mitochondria. Unlike CoQ(0), which is considered a mitochondrial membrane permeability transition inhibitor, the new compounds were inducers. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.08.012
• 作为产物：
  描述：

  N,N-二甲基甲酰胺 、 2-chloro-6-methylimidazo[2,1-b]thiazole 在 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 8.0h， 以65%的产率得到2-chloro-6-methylimidazo[2,1-b]thiazole-5-carboxaldehyde
  参考文献：
  名称：

  Effects of new ubiquinone-imidazo[2,1-b]thiazoles on mitochondrial complex I (NADH-ubiquinone reductase) and on mitochondrial permeability transition pore

  摘要：

  In this work we describe the synthesis of a series of imidazo[2,1-b]thiazoles and 2,3-dihydroimidazo[2,1-b]thiazoles connected by means of a methylene bridge to CoQ(0). These compounds were tested as specific inhibitors of the NADH:ubiquinone reductase activity in mitochondrial membranes. The imidazothiazole system when bound to the quinone ring in place of the isoprenoid lateral side chain, may increase the inhibitory effect (with an IC50 for NADH-Q(1) activity ranging between 0.25 and 0.96 muM) whereas the benzoquinone moiety seems to lose the capability to accept electrons from complex I as indicated by very low maximal velocity elicited by the compounds tested. Moreover the low rotenone sensitivity for almost all of these compounds suggests that they are only partially able to interact with the physiological ubiquinone-reduction site. The compounds were investigated for the capability of increasing the permeability transition of the inner mitochondrial membrane in isolated mitochondria. Unlike CoQ(0), which is considered a mitochondrial membrane permeability transition inhibitor, the new compounds were inducers. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.08.012

文献信息

• Antitumor Activity of New Substituted 3-(5-Imidazo[2,1-<i>b</i>]thiazolylmethylene)-2-indolinones and Study of Their Effect on the Cell Cycle
  作者：Aldo Andreani、Massimiliano Granaiola、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Vida Garaliene、William Welsh、Sonia Arora、Giovanna Farruggia、Lanfranco Masotti

  DOI：10.1021/jm050353e

  日期：2005.8.1

  This paper reports the synthesis of a new series of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones which were tested as potential antitumor agents at the National Cancer Institute. Two derivatives are now under review by BEC (Biological Evaluation Committee of NCI). To investigate the mechanism of action, the effect on cell cycle progression was studied by monitoring them in colon adenocarcinoma

  本文报道了一系列新的3-（5-咪唑并[2,1-b]噻唑基亚甲基）-2-吲哚满酮的合成方法，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。BEC（NCI生物评估委员会）目前正在审查两种衍生物。为了研究其作用机理，通过在结肠腺癌HT-29中监测它们来研究其对细胞周期进程的影响：两者均能够阻断有丝分裂中的HT-29。3-[（2,6-二甲基咪唑并[2,1-b]噻唑-5-基）亚甲基] -5-氯-2-吲哚满酮是活性最高的化合物。
• 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.
• Effects of new ubiquinone-imidazo[2,1-b]thiazoles on mitochondrial complex I (NADH-ubiquinone reductase) and on mitochondrial permeability transition pore
  作者：Aldo Andreani、Massimiliano Granaiola、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Maurizio Recanatini、Giorgio Lenaz、Romana Fato、Christian Bergamini

  DOI：10.1016/j.bmc.2004.08.012

  日期：2004.11

  In this work we describe the synthesis of a series of imidazo[2,1-b]thiazoles and 2,3-dihydroimidazo[2,1-b]thiazoles connected by means of a methylene bridge to CoQ(0). These compounds were tested as specific inhibitors of the NADH:ubiquinone reductase activity in mitochondrial membranes. The imidazothiazole system when bound to the quinone ring in place of the isoprenoid lateral side chain, may increase the inhibitory effect (with an IC50 for NADH-Q(1) activity ranging between 0.25 and 0.96 muM) whereas the benzoquinone moiety seems to lose the capability to accept electrons from complex I as indicated by very low maximal velocity elicited by the compounds tested. Moreover the low rotenone sensitivity for almost all of these compounds suggests that they are only partially able to interact with the physiological ubiquinone-reduction site. The compounds were investigated for the capability of increasing the permeability transition of the inner mitochondrial membrane in isolated mitochondria. Unlike CoQ(0), which is considered a mitochondrial membrane permeability transition inhibitor, the new compounds were inducers. (C) 2004 Elsevier Ltd. All rights reserved.