6-(4-(trifluoromethyl)phenyl)imidazo[2,1-b]thiazole | 1308398-12-0

• 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-(trifluoromethyl)phenyl)imidazo[2,1-b]thiazole
• 英文别名: 6-[4-(Trifluoromethyl)phenyl]imidazo[2,1-b][1,3]thiazole
• CAS: 1308398-12-0
• 化学式: C₁₂H₇F₃N₂S
• mdl: MFCD23148733
• 分子量: 268.262
• InChiKey: GKVSMKPDDNNWOC-UHFFFAOYSA-N

物化性质

• 熔点：
  165-175 °C
• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(4-(trifluoromethyl)phenyl)imidazo[2,1-b]thiazole 在 四丁基溴化铵 作用下， 以 乙腈 为溶剂， 以70%的产率得到5-bromo-6-(4-(trifluoromethyl)phenyl)imidazo[2,1-b]thiazole
  参考文献：
  名称：

  咪唑-杂芳烃的无金属区域选择性溴化：有机溴化物盐在电催化中的双重作用

  摘要：

  本文通过证明有机溴化物盐的双重作用来代表电化学转化，即四氮-丁基溴化铵 (TBAB)，作为溴化剂和电解质，用于几种咪唑杂芳族基序的区域选择性溴化。该方法不使用过渡金属/外部氧化剂，而是通过阳极氧化和阴极还原利用电子空穴和电子在环境温度下以良好至极好的产率形成所需的产物。该方法简单、环境友好且与各种官能团兼容。这种可持续的绿色溴化技术的意义在于，现成的低成本电极 (C(+)/C(-)) 可以重复使用多达 40 次而不会损失任何电化学活性。电氧化方法可以有效地扩大规模，也可以扩展到氯化。而且，

  DOI：

  10.1039/d1gc01069g
• 作为产物：
  描述：

  2-溴-4'-(三氟甲基)苯乙酮 在 lithium aluminium tetrahydride 、 potassium tert-butylate 、 氧气 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 22.0h， 生成 6-(4-(trifluoromethyl)phenyl)imidazo[2,1-b]thiazole
  参考文献：
  名称：

  含杂芳基的伯醇和仲醇中的无金属好氧氧化选择性C–C键裂解。

  摘要：

  据报道，伯和仲杂芳基醇中无过渡金属的需氧氧化选择性C–C键断裂反应。该反应是高效的并且耐受各种杂芳基醇，产生羧酸衍生物和中性杂芳族化合物。实验研究与密度泛函理论计算相结合，揭示了选择性C–C键断裂的机理。该策略还提供了另一种简单的羧化反应方法。

  DOI：

  10.1021/acs.orglett.9b00563

文献信息

• Novel Chlorination of Imidazo‐Fused Heterocycles via Dichloro(aryl)‐λ ³ ‐iodanes
  作者：Peng‐Fei Dai、Huiqin Xu

  DOI：10.1002/ejoc.202200779

  日期：2022.8.12

  An efficient protocol for chlorination of imidazo-fused heterocycles with dichloro(4-(trifluoromethyl)phenyl)-λ3-iodanes has been developed under very mild conditions. The present approach avoids the need of toxic chlorinating reagents, strong stoichiometric oxidants, metal catalysts and harsh reaction conditions. Control experiments indicate that the chlorinated reaction proceeds through an electrophilic

  已经在非常温和的条件下开发了一种用二氯（4-（三氟甲基）苯基）-λ 3 -碘烷氯化咪唑稠合杂环的有效方案。本方法避免了对有毒氯化试剂、强化学计量氧化剂、金属催化剂和苛刻反应条件的需要。对照实验表明氯化反应通过亲电芳香取代进行。
• Discovery of Novel Human Constitutive Androstane Receptor Agonists with the Imidazo[1,2-<i>a</i>]pyridine Structure
  作者：Ivana Mejdrová、Jan Dušek、Kryštof Škach、Alžbeta Stefela、Josef Skoda、Karel Chalupský、Klára Dohnalová、Ivona Pavkova、Thales Kronenberger、Azam Rashidian、Lucie Smutná、Vojtěch Duchoslav、Tomas Smutny、Petr Pávek、Radim Nencka

  DOI：10.1021/acs.jmedchem.2c01140

  日期：2023.2.23

  The nuclear constitutive androstane receptor (CAR, NR1I3) plays significant roles in many hepatic functions, such as fatty acid oxidation, biotransformation, liver regeneration, as well as clearance of steroid hormones, cholesterol, and bilirubin. CAR has been proposed as a hypothetical target receptor for metabolic or liver disease therapy. Currently known prototype high-affinity human CAR agonists

  核组成型雄烷受体 (CAR, NR1I3) 在许多肝功能中起着重要作用，例如脂肪酸氧化、生物转化、肝再生以及类固醇激素、胆固醇和胆红素的清除。CAR 已被提议作为代谢或肝病治疗的假设目标受体。目前已知的原型高亲和力人CAR激动剂如CITCO(6-(4-chlorophenyl)imidazo[2,1- b ][1,3]thiazole-5-carbaldehyde- O- (3,4-dichlorobenzyl)oxime)具有有限的选择性，激活孕烷 X 受体 (PXR) 受体，NR1I 亚家族的相关受体。我们发现了 3-(1 H -1,2,3-triazol-4-yl)imidazo[1,2- a的几种衍生物]在纳摩尔浓度下直接激活人类 CAR 的吡啶。虽然化合物39在人源化 CAR 小鼠和人类肝细胞中调节 CAR 靶基因，但它不会激活其他核受体，并且在细胞和遗传毒性测定以及啮齿动物毒性
• Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies
  作者：Dongdong Liang、Linhao Li、Caitlin Lynch、Bryan Mackowiak、William D. Hedrich、Yong Ai、Yue Yin、Scott Heyward、Menghang Xia、Hongbing Wang、Fengtian Xue

  DOI：10.1016/j.ejmech.2019.06.031

  日期：2019.10

  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.
• DL5050, a Selective Agonist for the Human Constitutive Androstane Receptor
  作者：Dongdong Liang、Linhao Li、Caitlin Lynch、Benjamin Diethelm-Varela、Menghang Xia、Fengtian Xue、Hongbing Wang

  DOI：10.1021/acsmedchemlett.9b00079

  日期：2019.7.11

  The constitutive androstane receptor (CAR) is a xenobiotic sensor governing the transcription of genes involved in drug disposition, energy homeostasis, and cell proliferation. However, currently available human CAR (hCAR) agonists are nonselective, which commonly activate hCAR along with other nuclear receptors, especially the closely related human pregnane X receptor (hPXR). Using a well-known hCAR agonist CITCO as a template, we report our efforts in the discovery of a potent and highly selective hCAR agonist. Two of the new compounds of the series, 18 and 19 (DL5050), demonstrated excellent potency and selectivity for hCAR over hPXR. DL5050 preferentially induced the expression of CYP2B6 (target of hCAR) over CYP3A4 (target of hPXR) on both the mRNA and protein levels. The selective hCAR agonist DL5050 represents a valuable tool molecule to further define the biological functions of hCAR, and may also be used as a new lead in the discovery of hCAR agonists for various therapeutic applications.
• 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.