(5aR,6S)-1-(4-fluorophenyl)-6-[(S)-1-methoxy-1-(thiophen-2-yl)ethyl]-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline*TFA salt | 1150845-19-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5aR,6S)-1-(4-fluorophenyl)-6-[(S)-1-methoxy-1-(thiophen-2-yl)ethyl]-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline*TFA salt
• 英文别名: (5aR,6S)-1-(4-fluorophenyl)-6-[(1S)-1-methoxy-1-thiophen-2-ylethyl]-5a-methyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-b]isoquinoline;2,2,2-trifluoroacetic acid
• CAS: 1150845-19-4
• 化学式: C₂HF₃O₂*C₂₅H₂₇FN₂OS
• 分子量: 536.591
• InChiKey: YISVMUVFWQFTEP-ZBNLYPIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.15
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  92.6
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (5aR,6S)-1-(4-fluorophenyl)-6-[(S)-1-methoxy-1-(thiophen-2-yl)ethyl]-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline 、 三氟乙酸 以 甲醇 、 水 为溶剂， 以15 mg的产率得到(5aR,6S)-1-(4-fluorophenyl)-6-[(S)-1-methoxy-1-(thiophen-2-yl)ethyl]-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline*TFA salt
  参考文献：
  名称：

  Novel Synthesis of the Hexahydroimidazo[1,5b]isoquinoline Scaffold: Application to the Synthesis of Glucocorticoid Receptor Modulators

  摘要：

  The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure - activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticold receptor (GR) in terms of binding affinity, although the partial agonist activity in the transrepressive assays depends on the substitution pattern on the B-ring. More importantly, most compounds in the HHII series bearing a tertiary alcohol moiety on the B-ring are either inactive or significantly less active in inducing GR-mediated transactivation, thus displaying a "dissociated" pharmacology in vitro.

  DOI：

  10.1021/jm901551w

文献信息

• Novel Synthesis of the Hexahydroimidazo[1,5b]isoquinoline Scaffold: Application to the Synthesis of Glucocorticoid Receptor Modulators
  作者：Hai-Yun Xiao、Dauh-Rurng Wu、Mary F. Malley、Jack Z. Gougoutas、Sium F. Habte、Mark D. Cunningham、John E. Somerville、John H. Dodd、Joel C. Barrish、Steven G. Nadler、T. G. Murali Dhar

  DOI：10.1021/jm901551w

  日期：2010.2.11

  The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure - activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticold receptor (GR) in terms of binding affinity, although the partial agonist activity in the transrepressive assays depends on the substitution pattern on the B-ring. More importantly, most compounds in the HHII series bearing a tertiary alcohol moiety on the B-ring are either inactive or significantly less active in inducing GR-mediated transactivation, thus displaying a "dissociated" pharmacology in vitro.