3-iodo-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine | 849628-13-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-iodo-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine
• 英文别名: 3-Iodo-2-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyridine
• CAS: 849628-13-3
• 化学式: C₁₄H₈F₃IN₂
• 分子量: 388.131
• InChiKey: CJJDPDLDXJWXCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  17.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-iodo-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium fluoride 、 copper(l) iodide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 3-(1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl)-2-(4-(trifluoromethyl)phenyl)imidazo[1,2- a]pyridine
  参考文献：
  名称：

  具有咪唑并 [1,2-a] 吡啶结构的新型人体组成型雄甾烷受体激动剂的发现

  摘要：

  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

  DOI：

  10.1021/acs.jmedchem.2c01140
• 作为产物：
  描述：

  2-溴-4'-(三氟甲基)苯乙酮 在 N-碘代丁二酰亚胺 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 生成 3-iodo-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine
  参考文献：
  名称：

  具有咪唑并 [1,2-a] 吡啶结构的新型人体组成型雄甾烷受体激动剂的发现

  摘要：

  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

  DOI：

  10.1021/acs.jmedchem.2c01140

文献信息

• Heterogeneous biomimetic aerobic synthesis of 3-iodoimidazo[1,2-a]pyridines via CuO_x/OMS-2-catalyzed tandem cyclization/iodination and their late-stage functionalization
  作者：Xu Meng、Chaoying Yu、Gexin Chen、Peiqing Zhao

  DOI：10.1039/c4cy00919c

  日期：——

  In this process, I2 not only plays the role of catalyst for the initial cyclization, with assistance from CuOx/OMS-2, but also acts as a reactant for the next electrophilic oxidative iodination, which makes the reaction highly atom economic. Besides, the late-stage functionalization of the I-substituted imidazo[1,2-a]pyridines is also demonstrated by various coupling reactions, which show its potential

  在基于氧化锰的八面体分子筛OMS-2（CuO x / OMS-2）上负载铜的情况下，由苯乙酮，2-氨基吡啶类化合物催化异构合成好氧合成3-碘咪唑并[1,2- a ]吡啶和我2通过以一锅方式实现串联环化/碘化。作为一种非均相催化剂，OMS-2不仅充当催化性铜物种的载体，而且还充当电子传递介体（ETM），该电子传递介体与Cu结合生成低能量途径以实现快速电子传递。这样，仿生催化氧化可在温和条件下直接将空气用作绿色末端氧化剂，并使用极低的催化剂负载量（0.2 mol％Cu）以中等至优异的收率为相应的产品提供宽底物。在此过程中，在CuO x的辅助下，I 2不仅起着初始环化催化剂的作用/ OMS-2，但也可作为下一个亲电子氧化碘化反应的反应物，这使该反应具有很高的原子经济性。此外，还通过各种偶联反应证明了I-取代的咪唑并[1,2- a ]吡啶的后期功能化，表明了其在合成和药物化学中的潜在应用。而且，该催化剂确实是非均质的并且可重复使用。
• [EN] SELECTIVE LIGANDS OF HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR<br/>[FR] LIGANDS SÉLECTIFS DU RÉCEPTEUR D'ANDROSTANE CONSTITUTIF HUMAIN
  申请人：USTAV ORGANICKE CHEMIE A BIOCHEMIE AV CR V V I

  公开号：WO2020221380A1

  公开（公告）日：2020-11-05

  The present invention provides a structurally novel class of heterocyclic compounds of general formula I wherein L1 is heteroaryl and L2 is heteroaryl or aryl. The novel compounds are useful in a method of prevention or treatment of a condition which is mediated by the action, or by loss of action, of Constitutive androstane receptor (CAR) receptor or its endogenous ligands. The present invention thus provides the novel compounds for medicinal use, as well as pharmaceutical composition containing said compounds. (I)

  本发明提供了一类结构新颖的杂环化合物，其通用公式为I，其中L1是杂芳基，L2是杂芳基或芳基。这些新颖化合物在预防或治疗由构成雄烷受体（CAR）受体或其内源性配体的作用或作用丧失介导的疾病的方法中是有用的。因此，本发明提供了用于药用的新颖化合物，以及含有所述化合物的药物组合物。(I)
• I₂O₅-Mediated Iodocyclization Cascade of <i>N</i>-(1-Arylallyl)pyridine-2-amines with Concomitant C═C Bond Cleavage: A Synthesis of 3-Iodoimidazo[1,2-<i>a</i>]pyridines
  作者：Bingwei Zhou、Yuan Yuan、Hongwei Jin、Yunkui Liu

  DOI：10.1021/acs.joc.9b00765

  日期：2019.5.3

  A facile method for the synthesis of 3-iodoimidazo[1,2-a]pyridines has been successfully developed involving an I2O5-mediated iodocyclization cascade of N-(1-arylallyl)pyridin-2-amines with concomitant C═C bond cleavage. Preliminary mechanistic studies reveal that this protocol might undergo an oxidative cyclization/decarboxylation/iodination sequence in which I2O5 is used as both an oxidant and an

  已成功开发了一种简便的合成3-碘咪唑并[1,2- a ]吡啶的方法，该方法涉及I 2 O 5介导的N-（1-芳基烯丙基）吡啶-2-胺与C═C的碘环化级联反应键断裂。初步的机理研究表明，该方案可能会经历氧化环化/脱羧/碘化过程，其中I 2 O 5既用作氧化剂，又用作碘源。本协议具有衬底范围广，操作简单和无金属条件的优点。
• 2,3-Diarylimidazo[1,2-a]pyridines as potential inhibitors of UV-induced keratinocytes apoptosis: synthesis, pharmacological properties and interactions with model membranes and oligonucleotides by NMR
  作者：Cécile Enguehard-Gueiffier、Florence Fauvelle、Jean-Claude Debouzy、André Peinnequin、Isabelle Thery、Vincent Dabouis、Alain Gueiffier

  DOI：10.1016/j.ejps.2004.10.009

  日期：2005.2

  Four 2,3-diarylimidazo[1,2-alpha]pyridines (I, 1a-c) were synthesized as inhibitors of UV-induced apoptosis and showed quite different properties. First, only the pyridinyl derivative I showed protection in molt cells. From the supposed intracellular target, phospholipid membrane models were studied by H-1, H-2 and P-31 NMR spectroscopy. All these molecules can incorporate the membrane bilayer of small unilamellar vesicles of lecithin (SUV). However, I is clearly closed to the external polar head of the lipids, and is relatively mobile in the layer. Conversely, the other molecules are strongly immobilized in the deep part of the external layer. P-31 solid-state NMR spectra recorded on phospholipid dispersions (multilayers vesicles (MLV)) completely excluded any detergent effect or any modification of temperature transition. The only structural or dynamic effect observed was a homogeneous, but limited, reduction in the chemical shift anisotropy in the presence of 1, in agreement with its superficial location. H-2 NMR experiment performed on the same model using perdeuterated phospholipids showed no significant fluidity reduction at the level of terminal CD3 groups in the presence of la-c, according to their deep location. Finaly, their interactions with synthetic oligonucleotide, d(CGATCG)(2) was studied showing non specific interactions of la on the external GC pair, while no interaction was observed with the other derivatives. (C) 2004 Elsevier B.V. All rights reserved.
• SELECTIVE LIGANDS OF HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR
  申请人：USTAV ORGANICKE CHEMIE A BIOCHEMIE AV CR, V.V.I.

  公开号：US20220185822A1

  公开（公告）日：2022-06-16

  A structurally novel class of heterocyclic compounds of general formula I wherein L1 is heteroaryl and L2 is heteroaryl or aryl is disclosed. The novel compounds are useful in a method of prevention or treatment of a condition that is mediated by the action, or by loss of action of Constitutive androstane receptor (CAR) receptor or its endogenous ligands. The present invention provides the novel compounds for medicinal use as well as pharmaceutical composition containing the compounds.