6-(甲氧羰基)-2-(4-甲基苯基)咪唑并[1,2-a]吡啶 | 917252-78-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 6-(甲氧羰基)-2-(4-甲基苯基)咪唑并[1,2-a]吡啶
• 英文名称: methyl 2-(4-methylphenyl)imidazo[1,2-a]pyridine-6-carboxylate
• 英文别名: methyl 2-(p-tolyl)imidazo[1,2-a]pyridine-6-carboxylate；2-p-tolyl-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester；methyl 2-(4-tolyl)imidazo[1,2-a]pyridine-6-carboxylate；6-(Methoxycarbonyl)-2-(4-methylphenyl)imidazo[1,2-A]pyridine
• CAS: 917252-78-9
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: GGBGKTKRISZKAC-UHFFFAOYSA-N

物化性质

• 熔点：
  191-192°C
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(甲氧羰基)-2-(4-甲基苯基)咪唑并[1,2-a]吡啶 在 吡啶 、 盐酸羟胺 、 sodium acetate 、 溶剂黄146 、 sodium hydroxide 、 锌 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors

  摘要：

  A new series of DPP‐4 inhibitors with imidazo[1,2‐a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2‐benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4‐dichlorophenyl group at the 2‐position as a potent (IC50 = 0.13 μm), selective (DPP‐8/DPP‐4 = 215 and DPP‐9/DPP‐4 = 192) and in vivo efficacious DPP‐4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP‐4 with the pyridine moiety of imidazo[1,2‐a]pyridine ring providing an additional π−π interaction with Phe357 of DPP‐4. Compound 5d might be a promising lead for further development of novel DPP‐4 inhibitor treating T2DM.

  DOI：

  10.1111/cbdd.12560
• 作为产物：
  描述：

  对甲基苯乙酮 在 sodium carbonate 、 copper(ll) bromide 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 生成 6-(甲氧羰基)-2-(4-甲基苯基)咪唑并[1,2-a]吡啶
  参考文献：
  名称：

  Discovery of novel potent GPR40 agonists containing imidazo[1,2-a]pyridine core as antidiabetic agents

  摘要：

  Free fatty acid receptor 1 (FFA1 or GPR40) has been studied for many years as a target for the treatment of type 2 diabetes mellitus. In order to increase potency and reduce hepatotoxicity, a series of novel compounds containing imidazo[1,2-a]pyridine scaffold as GPR40 agonist were synthesized. Compound I-14 was identified as an effective agonist as shown by the conspicuous drop in blood glucose in normal and diabetic mice. It had no risk of hepatotoxicity compared with TAK-875. Moreover, good pharmacokinetic (PK) properties of I-14 were observed (CL = 27.26 ml/h/kg, t1/2 = 5.93 h). The results indicate that I-14 could serve as a possible candidate to treat diabetes.

  DOI：

  10.1016/j.bmc.2020.115574

文献信息

• ANTITUMOR DERIVATIVES FOR DIFFERENTIATION THERAPY
  申请人：THE CLEVELAND CLINIC FOUNDATION

  公开号：US20170253589A1

  公开（公告）日：2017-09-07

  Imidazopyridine derivatives according to formula I are described wherein X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R 1 and optional R 2 are independently selected from H, OH, substituted or unsubstituted C 1 -C 6 alkyl, and substituted or unsubstituted C 4 -C 6 cycloalkyl or cycloheteroalkyl, R 3 is selected from H, OH, substituted or unsubstituted C 1 -C 6 alkyl, and optional Z is selected from OH, NH 2 , NH(CO)R 4 , NH(SO 2 )R 4 , guanidine, alkylguanidine, and fluoroguanidine, R 4 is polyethylene glycol or substituted or unsubstituted C 1 -C 6 alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.

  根据公式I描述的咪唑吡啶衍生物，其中X选自CH、N、S和O，Y选自S、CO和O，R1和可选的R2分别选自H、OH、取代或未取代的C1-C6烷基，以及取代或未取代的C4-C6环烷基或环杂烷基，R3选自H、OH、取代或未取代的C1-C6烷基，可选的Z选自OH、NH2、NH(CO)R4、NH(SO2)R4、胍、烷基胍和氟代胍，R4为聚乙二醇或取代或未取代的C1-C6烷基，及其药用盐。这些咪唑吡啶衍生物可用于治疗受试者的癌症。
• Major Metabolites of Zolpidem: Expeditious Synthesis and Mass Spectra
  作者：Frédérique Klupsch、Raymond Houssin、Luc Humbert、Michel Imbenotte、Jean-Pierre Hénichart、Michel Lhermitte

  DOI：10.1248/cpb.54.1318

  日期：——

  An expeditious route to the two major metabolites of Zolpidem—and readily applicable to the synthesis of the drug—was established via a cyclization reaction between a 2-aminopyridine and a suitable α-bromoacetophenone. The structures of the target compounds were confirmed from a 2D 1H–15N NMR correlation. Their mass spectra contribute to a reliable toxicological identification of the drug in the case of drug-facilitated crimes.

  通过2-氨基吡啶与适当的α-溴乙酰苯酮之间的环化反应，建立了一条快速合成唑吡坦两个主要代谢物的路线，并且该路线可直接应用于药物的合成。目标化合物的结构通过二维^1H–^15N NMR相关进行确认。它们的质谱为药物在药物促进犯罪中的可靠毒理学鉴定提供了支持。
• Imidazo[1,2-a]pyridines and their use as pharmaceuticals
  申请人：sanofi-aventis

  公开号：EP1964840A1

  公开（公告）日：2008-09-03

  Imidazo[1,2-a]pyridines and their use as pharmaceuticals The present invention relates to derivatives of imidazo[1,2-a]pyridines of the formula (I), in which R, R1 to R4 and n have the meanings indicated in the claims, which modulate the transcription of endothelial nitric oxide (NO) synthase and are valuable pharmacologically active compounds. Specifically, the compounds of the formula I upregulate the expression of the enzyme endothelial NO synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention further relates to processes for the preparation of compounds of the formula I, to pharmaceutical compositions comprising them, and to the use of compounds of the formula I for the manufacture of a medicament for the stimulation of the expression of endothelial NO synthase or for the treatment of various diseases including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency, for example.

  咪唑[1,2-a]吡啶及其作为药物的用途。本发明涉及咪唑[1,2-a]吡啶衍生物的公式(I)，其中R、R1至R4和n具有声明中指示的含义，这些衍生物调节内皮型一氧化氮(NO)合酶的转录，并且是有价值的药理活性化合物。具体来说，公式I的化合物上调内皮型NO合酶酶的表达，并可应用于需要增加该酶的表达或增加NO水平或正常化降低的NO水平的情况。该发明还涉及公式I化合物的制备方法，包括它们的药物组合物，以及公式I化合物用于制造刺激内皮型NO合酶表达或治疗各种疾病的药物，包括心血管疾病如动脉粥样硬化、血栓形成、冠状动脉疾病、高血压和心脏功能不全等。
• Design, synthesis, and biological evaluation of novel dual FFA1 (GPR40)/PPARδ agonists as potential anti-diabetic agents
  作者：Zheng Li、Lijun Hu、Xuekun Wang、Zongtao Zhou、Liming Deng、Yawen Xu、Luyong Zhang

  DOI：10.1016/j.bioorg.2019.103254

  日期：2019.11

  free fatty acid receptor 1 (FFA1) and peroxisome proliferator-activated receptor δ (PPARδ) were considered as potential anti-diabetic targets, and the dual FFA1/PPARδ agonists might provide synergistic effect in insulin secretion and sensibility. Herein, we further develop dual agonists by screening 7 series of heterocycles, resulting in the discovery of compound 19 with considerable oral pharmacokinetic

  游离脂肪酸受体1（FFA1）和过氧化物酶体增殖物激活受体δ（PPARδ）被认为是潜在的抗糖尿病靶标，而双重FFA1 /PPARδ激动剂可能在胰岛素分泌和敏感性方面提供协同作用。在本文中，我们通过筛选7个杂环系列进一步开发了双重激动剂，从而发现了具有相当大的口服药代动力学特征的化合物19。化合物19在FFA1和PPARδ之间显示出平衡的效能，并且对PPARα和PPARγ具有高选择性。此外，化合物19以剂量依赖性的方式发挥了改善的降糖作用和胰岛素敏感性，这可能归因于其同时调节胰岛素分泌和抵抗力的双重作用。我们的结果扩展了现有的化学空间，并提供了一种有效的工具化合物19。
• IMMUNOASSAY WITH EXTENDED DETECTION WINDOW
  申请人：Fitzgerald Stephen Peter

  公开号：US20110189794A1

  公开（公告）日：2011-08-04

  The immunoassay method and kit are provided for the detection and/or the determination of zolpidem. The disclosure provides novel antibodies, derived from a novel immunogen, that are highly sensitive and bind to zolpidem and its main urinary metabolite [3-(2-N,N-dimethylamino-2-oxoethyl)-6-methylimidazo[1,2-a]pyridin-2-yl]benzoic acid, enabling an extension of the detection window of zolpidem in individuals who have abused the drug, or have been victim of its side-effects or its criminal misuse.

  提供了用于检测和/或测定唑吡坦的免疫分析方法和试剂盒。该公开提供了源自新型免疫原的新型抗体，这些抗体对唑吡坦及其主要尿代谢物[3-(2-N,N-二甲基氨基-2-氧乙基)-6-甲基咪唑[1,2-a]吡啶-2-基]苯甲酸具有高灵敏度并结合，从而延长了滥用该药物的个体中唑吡坦的检测窗口，或者是受其副作用或非法滥用的受害者。