(2-amino-6-[9-(4-nitrophenoxy)nonyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(3,4-dichlorophenyl)-methanone | 1223426-10-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-amino-6-[9-(4-nitrophenoxy)nonyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(3,4-dichlorophenyl)-methanone
• 英文别名: [2-amino-6-[9-(4-nitrophenoxy)nonyl]-5,7-dihydro-4H-thieno[2,3-c]pyridin-3-yl]-(3,4-dichlorophenyl)methanone
• CAS: 1223426-10-5
• 化学式: C₂₉H₃₃Cl₂N₃O₄S
• 分子量: 590.571
• InChiKey: LJDQXSIHJOQHRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-amino-6-[9-(4-nitrophenoxy)nonyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(3,4-dichlorophenyl)-methanone 在 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 生成 (2-amino-6-[9-(4-aminophenoxy)nonyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(3,4-dichlorophenyl)-methanone
  参考文献：
  名称：

  Hybrid Ortho/Allosteric Ligands for the Adenosine A₁ Receptor

  摘要：

  Many G protein-coupled receptors (GPCRs), including the adenosine A(1) receptor (A(1)AR), have been shown to be allosterically modulated by small molecule ligands. So far, in the absence of structural information, the exact location of the allosteric site on the A(1)AR is not known. We synthesized a series of bivalent ligands (4) with an increasing linker length between the orthosteric and allosteric pharmacophores and used these as tools to search for the allosteric site on the A(1)AR. The compounds were tested in both equilibrium radioligand displacement and functional assays in the absence and presence of a reference allosteric enhancer, (2-amino-4,5-dimethy1-3-thienyl)-[3-(trifluoromethyl)phenyl]methanone, PD81,723 (1). Bivalent ligand N-6-[2-amino-3-(3,4-dichlorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]-pyridin-6-yl-9-nonyloxy-4-phenyl]-adenosine 4h (LUF6258) with a 9 carbon atom spacer did not show significant changes in affinity or potency in the presence of 1, indicating that this ligand bridged both sites on the receptor. Furthermore, 4h displayed an increase in efficacy, but not potency, compared to the parent, monovalent agonist 2. From molecular modeling studies, we speculate that the allosteric site of the A(1)AR is located in the proximity of the orthosteric site, possibly within the boundaries of the second extracellular loop of the receptor.

  DOI：

  10.1021/jm901252a
• 作为产物：
  描述：

  1-[9-(4-nitrophenoxy)nonyl]piperidin-4-one 、 3,4-二氯苯甲酰乙腈 在 sulfur 、 二乙胺 作用下， 以 乙醇 为溶剂， 以17%的产率得到(2-amino-6-[9-(4-nitrophenoxy)nonyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-3-yl)-(3,4-dichlorophenyl)-methanone
  参考文献：
  名称：

  Hybrid Ortho/Allosteric Ligands for the Adenosine A₁ Receptor

  摘要：

  Many G protein-coupled receptors (GPCRs), including the adenosine A(1) receptor (A(1)AR), have been shown to be allosterically modulated by small molecule ligands. So far, in the absence of structural information, the exact location of the allosteric site on the A(1)AR is not known. We synthesized a series of bivalent ligands (4) with an increasing linker length between the orthosteric and allosteric pharmacophores and used these as tools to search for the allosteric site on the A(1)AR. The compounds were tested in both equilibrium radioligand displacement and functional assays in the absence and presence of a reference allosteric enhancer, (2-amino-4,5-dimethy1-3-thienyl)-[3-(trifluoromethyl)phenyl]methanone, PD81,723 (1). Bivalent ligand N-6-[2-amino-3-(3,4-dichlorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]-pyridin-6-yl-9-nonyloxy-4-phenyl]-adenosine 4h (LUF6258) with a 9 carbon atom spacer did not show significant changes in affinity or potency in the presence of 1, indicating that this ligand bridged both sites on the receptor. Furthermore, 4h displayed an increase in efficacy, but not potency, compared to the parent, monovalent agonist 2. From molecular modeling studies, we speculate that the allosteric site of the A(1)AR is located in the proximity of the orthosteric site, possibly within the boundaries of the second extracellular loop of the receptor.

  DOI：

  10.1021/jm901252a

文献信息

• Hybrid Ortho/Allosteric Ligands for the Adenosine A₁ Receptor
  作者：Rajeshwar Narlawar、J. Robert Lane、Munikumar Doddareddy、Judy Lin、Johannes Brussee、Adriaan P. IJzerman

  DOI：10.1021/jm901252a

  日期：2010.4.22

  Many G protein-coupled receptors (GPCRs), including the adenosine A(1) receptor (A(1)AR), have been shown to be allosterically modulated by small molecule ligands. So far, in the absence of structural information, the exact location of the allosteric site on the A(1)AR is not known. We synthesized a series of bivalent ligands (4) with an increasing linker length between the orthosteric and allosteric pharmacophores and used these as tools to search for the allosteric site on the A(1)AR. The compounds were tested in both equilibrium radioligand displacement and functional assays in the absence and presence of a reference allosteric enhancer, (2-amino-4,5-dimethy1-3-thienyl)-[3-(trifluoromethyl)phenyl]methanone, PD81,723 (1). Bivalent ligand N-6-[2-amino-3-(3,4-dichlorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]-pyridin-6-yl-9-nonyloxy-4-phenyl]-adenosine 4h (LUF6258) with a 9 carbon atom spacer did not show significant changes in affinity or potency in the presence of 1, indicating that this ligand bridged both sites on the receptor. Furthermore, 4h displayed an increase in efficacy, but not potency, compared to the parent, monovalent agonist 2. From molecular modeling studies, we speculate that the allosteric site of the A(1)AR is located in the proximity of the orthosteric site, possibly within the boundaries of the second extracellular loop of the receptor.