4-(3-cyclohexyl-[1,2,4]oxadiazol-5-yl)piperidine | 276237-04-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(3-cyclohexyl-[1,2,4]oxadiazol-5-yl)piperidine
• 英文别名: 3-cyclohexyl-5-(piperidin-4-yl)-1,2,4-oxadiazole；4-(3-Cyclohexyl-1,2,4-oxadiazol-5-yl)piperidine；3-cyclohexyl-5-piperidin-4-yl-1,2,4-oxadiazole
• CAS: 276237-04-8
• 化学式: C₁₃H₂₁N₃O
• mdl: MFCD11046773
• 分子量: 235.329
• InChiKey: FFXHDVOOCRRMLJ-UHFFFAOYSA-N

物化性质

• 沸点：
  385.2±52.0 °C(Predicted)
• 密度：
  1.083±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.846
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,4,4-三氟丁酸 、 4-(3-cyclohexyl-[1,2,4]oxadiazol-5-yl)piperidine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以45%的产率得到1-[4-(3-cyclohexyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-4,4,4-trifluorobutan-1-one
  参考文献：
  名称：

  Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors

  摘要：

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.

  DOI：

  10.1021/jm200825u
• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(3-cyclohexyl-[1,2,4]oxadiazol-5-yl)piperidine
  参考文献：
  名称：

  Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors

  摘要：

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.

  DOI：

  10.1021/jm200825u

文献信息

• NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS
  申请人：Son Jung Beom

  公开号：US20130274268A1

  公开（公告）日：2013-10-17

  The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.

  本发明涉及一种用于调节G蛋白偶联受体的双环化合物。该创新化合物可用于预防或治疗与调节G蛋白偶联受体相关的疾病，特别是GPR119 G蛋白偶联受体。
• Discovery of orally active sulfonylphenyl thieno[3,2-d]pyrimidine derivatives as GPR119 agonists
  作者：Heecheol Kim、Minjung Kim、Kyujin Oh、Sohee Lee、Sunyoung Lim、Sangdon Lee、Young Hoon Kim、Kwee Hyun Suh、Kyung Hoon Min

  DOI：10.1016/j.ejmech.2023.115584

  日期：2023.10

  G-protein-coupled receptor 119 (GPR119) has great potential as a therapeutic target for the treatment of type II diabetes. Novel thieno[3,2-d]pyrimidine derivatives were discovered as GPR119 agonists through a bioisosteric replacement strategy. The sulfonylphenyl thieno[3,2-d] pyrimidine scaffold was introduced, and its derivatives exhibited potent agonistic activity for GPR119 in cell-based assays. The representative

  G蛋白偶联受体119（GPR119）作为治疗II型糖尿病的治疗靶点具有巨大潜力。通过生物等排替代策略发现了新型噻吩并[3,2-d]嘧啶衍生物作为 GPR119 激动剂。引入了磺酰基苯基噻吩并[3,2-d]嘧啶支架，其衍生物在基于细胞的测定中对 GPR119 显示出有效的激动活性。代表性衍生物43在啮齿动物中表现出优异的药代动力学特征，并显着改善体内葡萄糖耐量。在OGTT 研究中，化合物43显着降低小鼠和大鼠的血糖水平。
• US8853213B2
  申请人：——

  公开号：US8853213B2

  公开（公告）日：2014-10-07
• [EN] NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS<br/>[FR] NOUVEAU COMPOSÉ BICYCLIQUE POUR LA MODULATION DE RÉCEPTEURS COUPLÉS À LA PROTÉINE G
  申请人：HANMI PHARM IND CO LTD

  公开号：WO2012093809A2

  公开（公告）日：2012-07-12

  The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.