tert-butyl [(2S,3S)-1-{(4′-propylbiphenyl-4-yl)-[(1R,2R)-2-(pyridin-2-yl)cyclopropanecarbonyl]amino}-3-methylpentan-2-yl]carbamate | 1287205-79-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl [(2S,3S)-1-{(4′-propylbiphenyl-4-yl)-[(1R,2R)-2-(pyridin-2-yl)cyclopropanecarbonyl]amino}-3-methylpentan-2-yl]carbamate
• 英文别名: ((1S,2S)-1-{[(4'-propylbiphenyl-4-yl)-(2-pyridin-2-ylcyclopropanecarbonyl)amino]methyl}-2-methylbutyl)carbamic acid tert-butyl ester；tert-butyl N-[(2S,3S)-3-methyl-1-[4-(4-propylphenyl)-N-[(1R,2R)-2-pyridin-2-ylcyclopropanecarbonyl]anilino]pentan-2-yl]carbamate
• CAS: 1287205-79-1
• 化学式: C₃₅H₄₅N₃O₃
• 分子量: 555.761
• InChiKey: ZQSKMVRGUOOIHI-OTJVGIONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl [(2S,3S)-1-{(4′-propylbiphenyl-4-yl)-[(1R,2R)-2-(pyridin-2-yl)cyclopropanecarbonyl]amino}-3-methylpentan-2-yl]carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以97 mg的产率得到(1R,2R)-2-(pyridin-2-yl)cyclopropanecarboxylic acid ((2S,3S)-2-amino-3-methylpentyl)-(4′-propylbiphenyl-4-yl)amide
  参考文献：
  名称：

  Synthesis, Pharmacological Characterization, and Structure–Activity Relationship Studies of Small Molecular Agonists for the Orphan GPR88 Receptor

  摘要：

  GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorders. The signal transduction pathway and receptor functions of GPR88, however, are still largely unknown due to the lack of endogenous and synthetic ligands. In this paper, we report the synthesis of a GPR88 agonist 2-PCCA and its pure diastereomers, which were functionally characterized in both transiently and stably expressing GPR88 HEK293 cells. 2-PCCA inhibited isoproterenol-stimulated cAMP accumulation in a concentration-dependent manner in cells expressing GPR88 but not in the control cells, suggesting that the observed cAMP inhibition is mediated through GPR88 and that GPR88 is coupled to G alpha(i). 2-PCCA did not induce calcium mobilization in GPR88 cells, indicating no G alpha(q)-mediated response. A structure activity relationship (SAR) study of 2-PCCA was also conducted to explore the key structural features for GPR88 agonist activity.

  DOI：

  10.1021/cn500082p
• 作为产物：
  描述：

  tert-butyl (1R,2R)-2-(pyridin-2-yl)cyclopropanecarboxylate 在 盐酸 、 potassium phosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 草酰氯 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.1h， 生成 tert-butyl [(2S,3S)-1-{(4′-propylbiphenyl-4-yl)-[(1R,2R)-2-(pyridin-2-yl)cyclopropanecarbonyl]amino}-3-methylpentan-2-yl]carbamate
  参考文献：
  名称：

  Synthesis, Pharmacological Characterization, and Structure–Activity Relationship Studies of Small Molecular Agonists for the Orphan GPR88 Receptor

  摘要：

  GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorders. The signal transduction pathway and receptor functions of GPR88, however, are still largely unknown due to the lack of endogenous and synthetic ligands. In this paper, we report the synthesis of a GPR88 agonist 2-PCCA and its pure diastereomers, which were functionally characterized in both transiently and stably expressing GPR88 HEK293 cells. 2-PCCA inhibited isoproterenol-stimulated cAMP accumulation in a concentration-dependent manner in cells expressing GPR88 but not in the control cells, suggesting that the observed cAMP inhibition is mediated through GPR88 and that GPR88 is coupled to G alpha(i). 2-PCCA did not induce calcium mobilization in GPR88 cells, indicating no G alpha(q)-mediated response. A structure activity relationship (SAR) study of 2-PCCA was also conducted to explore the key structural features for GPR88 agonist activity.

  DOI：

  10.1021/cn500082p

文献信息

• [EN] MODULATORS OF G PROTEIN-COUPLED RECEPTOR 88<br/>[FR] MODULATEURS DE RÉCEPTEUR 88 COUPLÉ AUX PROTÉINES G
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011044212A1

  公开（公告）日：2011-04-14

  The present disclosure is generally directed to compounds which can modulate G-protein coupled receptor 88, compositions comprising such compounds, and methods for modulating G-protein coupled receptor 88.

  本公开涉及的是能够调节G蛋白偶联受体88的化合物，包含这种化合物的组合物，以及调节G蛋白偶联受体88的方法。
• Modulators of G Protein-Coupled Receptor 88
  申请人：Bi Yingzhi

  公开号：US20110251204A1

  公开（公告）日：2011-10-13

  The present disclosure is generally directed to compounds which can modulate G-protein coupled receptor 88, compositions comprising such compounds, and methods for modulating G-protein coupled receptor 88.

  本公开涉及一般性的化合物，可以调节G-蛋白偶联受体88，包括这些化合物的组合物和调节G-蛋白偶联受体88的方法。
• MODULATORS OF G PROTEIN-COUPLED RECEPTOR 88
  申请人：Bristol-Myers Squibb Company

  公开号：EP2486014B1

  公开（公告）日：2013-07-31
• US8426414B2
  申请人：——

  公开号：US8426414B2

  公开（公告）日：2013-04-23