2-(4-cyclohexyl-phenyl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester | 900019-66-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 2-(4-cyclohexyl-phenyl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester
• 英文别名: Methyl 2-(4-cyclohexylphenyl)imidazo[1,2-a]pyridine-6-carboxylate
• CAS: 900019-66-1
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: JPRJISIWZBJFLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  2-(4-cyclohexyl-phenyl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester 在 lithium aluminium tetrahydride 作用下， 以 乙酸乙酯 为溶剂， 生成 [2-(4-Cyclohexylphenyl)imidazo[1,2-a]pyridin-6-yl]methanol
  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
• 作为产物：
  描述：

  4'-环己基苯乙酮 在 sodium carbonate 、 copper(ll) bromide 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 生成 2-(4-cyclohexyl-phenyl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester
  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

• 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。
• IMIDAZO[1,2-a]PYRIDINES AND THEIR USE AS PHARMACEUTICALS
  申请人：ZOLLER Gerhard

  公开号：US20100113412A1

  公开（公告）日：2010-05-06

  The present invention relates to derivatives of imidazo[1,2-a]pyridines of 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 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 formula I, to pharmaceutical compositions comprising them, and to the use of compounds of formula I 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.

  本发明涉及公式I的咪唑[1,2-a]吡啶衍生物，其中R、R1至R4和n具有所述权利要求中所示的含义，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。具体地，公式I的化合物上调内皮型NO合酶的表达，并可应用于需要增加该酶的表达或增加NO水平或恢复降低的NO水平的情况。本发明还涉及制备公式I的化合物的方法，包括它们的制药组合物，以及使用公式I的化合物刺激内皮型NO合酶的表达或治疗各种疾病，包括心血管疾病，如动脉粥样硬化、血栓形成、冠状动脉疾病、高血压和心脏衰竭等。
• IMIDAZO[1,2-A]PYRIDINES AND THEIR USE AS PHARMACEUTICALS
  申请人：Sanofi-Aventis

  公开号：EP2129375A1

  公开（公告）日：2009-12-09
• US8399476B2
  申请人：——

  公开号：US8399476B2

  公开（公告）日：2013-03-19
• [EN] IMIDAZO[1,2-A] PYRIDINES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] IMIDAZO[1,2-A] PYRIDINES ET LEUR UTILISATION EN TANT QUE PRODUITS PHARMACEUTIQUES
  申请人：SANOFI AVENTIS

  公开号：WO2008104278A1

  公开（公告）日：2008-09-04

  [EN] 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.
  [FR] La présente invention concerne des dérivés d'imidazo[1,2-a]pyridines de formule (I), dans laquelle R, R1 à R4 et n ont les significations indiquées dans les revendications, ces dérivés modulant la transcription de la synthase de l'oxyde nitrique endothélial et constituant des composés précieux, actifs pharmacologiquement. Plus spécifiquement, les composés de la formule (I) régulent positivement l'expression de la synthase de l'oxyde nitrique endothélial et peuvent être utilisés dans des conditions où est souhaitée une expression accentuée de l'enzyme ou un niveau d'oxyde nitrique accru ou de la normalisation un niveau d'oxyde nitrique réduit. Cette invention concerne aussi des procédés de préparation de composés de formule (I), des compositions pharmaceutiques les contenant et l'utilisation des composés de formule (I) dans la fabrication d'un médicament destiné à la stimulation de l'expression de la synthase de l'oxyde nitrique endothélial ou au traitement de divers maladies, notamment des troubles cardio-vasculaires telles que l'athérosclérose, la thrombose, la coronaropathie, l'hypertension et l'insuffisance cardiaque, par exemple.