(RS)-2-{[(9H-fluoren-9-yl)methoxy]carbonyl}-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid | 1199776-90-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (RS)-2-{[(9H-fluoren-9-yl)methoxy]carbonyl}-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid
• 英文别名: 2-(((9H-fluoren-9-yl)methoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid；2-(9H-fluoren-9-ylmethoxycarbonyl)-3,4-dihydro-1H-isoquinoline-4-carboxylic acid
• CAS: 1199776-90-3
• 化学式: C₂₅H₂₁NO₄
• 分子量: 399.446
• InChiKey: NUOJTTAZVSDNDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异唑-5-羧酸 、 (RS)-2-{[(9H-fluoren-9-yl)methoxy]carbonyl}-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid 、 FMOC-Β-环己基-L-丙氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.09h， 生成 N-[(2S)-1-(4-carbamoyl-3,4-dihydroisoquinolin-2(1H)-yl)-3-cyclohexyl-1-oxopropan-2-yl]isoxazole-5-carboxamide 、 N-[(2S)-1-(4-carbamoyl-3,4-dihydroisoquinolin-2(1H)-yl)-3-cyclohexyl-1-oxopropan-2-yl]isoxazole-5-carboxamide
  参考文献：
  名称：

  Discovery of Novel Nonpeptidic PAR2 Ligands

  摘要：

  Proteinase-activated receptor 2 (PAR2) is a class A G protein-coupled receptor whose activation has been associated with inflammatory diseases and cancer, thus representing a valuable therapeutic target. Pathophysiological roles of PAR2 are often characterized using peptidic PAR2 agonists. Peptidic ligands are frequently unstable in vivo and show poor bioavailability, and only a few approaches toward drug-like nonpeptidic PAR2 ligands have been described. The herein-described ligand 5a (IK187) is a nonpeptidic PAR2 agonist with submicromolar potency in a functional assay reflecting G protein activation. The ligand also showed substantial ss-arrestin recruitment. The development of the compound was guided by the crystal structure of PAR2, when the C-terminal end of peptidic agonists was replaced by a small molecule based on a disubstituted phenylene scaffold. IK187 shows preferable metabolic stability and may serve as a lead compound for the development of nonpeptidic drugs addressing PAR2.

  DOI：

  10.1021/acsmedchemlett.0c00154
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 1,2,3,4-四氢异喹啉-4-羧酸 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以98%的产率得到(RS)-2-{[(9H-fluoren-9-yl)methoxy]carbonyl}-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid
  参考文献：
  名称：

  Discovery of Novel Nonpeptidic PAR2 Ligands

  摘要：

  Proteinase-activated receptor 2 (PAR2) is a class A G protein-coupled receptor whose activation has been associated with inflammatory diseases and cancer, thus representing a valuable therapeutic target. Pathophysiological roles of PAR2 are often characterized using peptidic PAR2 agonists. Peptidic ligands are frequently unstable in vivo and show poor bioavailability, and only a few approaches toward drug-like nonpeptidic PAR2 ligands have been described. The herein-described ligand 5a (IK187) is a nonpeptidic PAR2 agonist with submicromolar potency in a functional assay reflecting G protein activation. The ligand also showed substantial ss-arrestin recruitment. The development of the compound was guided by the crystal structure of PAR2, when the C-terminal end of peptidic agonists was replaced by a small molecule based on a disubstituted phenylene scaffold. IK187 shows preferable metabolic stability and may serve as a lead compound for the development of nonpeptidic drugs addressing PAR2.

  DOI：

  10.1021/acsmedchemlett.0c00154