2-Methyl-6-chloroimidazo<2,1-b>thiazole-5-carboxaldehyde | 123772-36-1

• 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-Methyl-6-chloroimidazo<2,1-b>thiazole-5-carboxaldehyde
• 英文别名: 6-chloro-2-methylimidazo[2,1-b]thiazole-5-carbaldehyde；6-chloro-2-methylimidazo[2,1-b][1,3]thiazole-5-carbaldehyde
• CAS: 123772-36-1
• 化学式: C₇H₅ClN₂OS
• 分子量: 200.649
• InChiKey: CFYCBRXFKYRXLM-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-Methyl-6-chloroimidazo<2,1-b>thiazole-5-carboxaldehyde 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-chloroimidazo<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：

  2-Methyl-6-chloroimidazo<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， 以60%的产率得到2-Methyl-6-chloroimidazo<2,1-b>thiazole-5-carboxaldehyde
  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：

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。
• Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents
  作者：Rita Morigi、Alessandra Locatelli、Alberto Leoni、Mirella Rambaldi、Roberta Bortolozzi、Elena Mattiuzzo、Roberto Ronca、Federica Maccarinelli、Ernest Hamel、Ruoli Bai、Andrea Brancale、Giampietro Viola

  DOI：10.1016/j.ejmech.2019.01.049

  日期：2019.3

  small library of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones has been synthesized and screened according to protocols available at the National Cancer Institute (NCI). Some derivatives were potent antiproliferative agents, showing GI50 values in the nanomolar range. Remarkably, when most active compounds against leukemia cells were tested in human peripheral blood lymphocytes from healthy donors

  根据国家癌症研究所（NCI）提供的协议，合成并筛选了3-（5-咪唑并[2,1- b ]噻唑基亚甲基）-2-吲哚满酮的小型文库。一些衍生物是有效的抗增殖剂，在纳摩尔范围内显示GI 50值。值得注意的是，当在健康捐献者的人外周血淋巴细胞中检测到大多数针对白血病细胞的活性化合物时，其细胞毒性要低100-200倍。NCI生物学评估委员会选择了一些化合物，以确定微管蛋白组装抑制作用。此外，对HeLa，HT-29和A549细胞进行的流式细胞术研究表明，化合物14和25在G2 / M阶段造成了封锁。有趣的是，这些衍生物通过线粒体死亡途径诱导细胞凋亡，同时引起caspase-3和-9的显着激活，PARP裂解以及抗凋亡蛋白Bcl-2和Mcl-1的下调。最后，还在小鼠BL6-B16黑色素瘤和E0771乳腺癌细胞中对化合物25进行了体内测试，在两种情况下均导致肿瘤体积显着减少。
• 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。
• 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.
• 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.