(S)-1-[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]-1-(thiophen-2-yl)ethanol | 1150845-16-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-1-[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]-1-(thiophen-2-yl)ethanol
• 英文别名: (S)-1-((5aR,6S)-1-(4-Fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-(thiophen-2-yl)ethanol；(1S)-1-[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-b]isoquinolin-6-yl]-1-thiophen-2-ylethanol
• CAS: 1150845-16-1
• 化学式: C₂₄H₂₅FN₂OS
• 分子量: 408.54
• InChiKey: VQXYALIFGGOXRU-OYDLWJJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-1-[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]-1-(thiophen-2-yl)ethanol 、 碘甲烷 在 sodium hydride 、 三氟乙酸 作用下， 以 N-甲基乙酰胺 、 甲醇 、 水 为溶剂， 以87%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
  参考文献：
  名称：

  NONSTEROIDAL COMPOUNDS USEFUL AS MODULATORS OF GLUCOCORTICOID RECEPTOR AP-1 AND/OR NF-KAPPAB ACITIVITY AND USE THEREOF

  摘要：

  公开的是具有以下结构的化合物（I）：其中：A和D中的一个是—N—，另一个是—C—；或其对映体、非对映体异构体或药用盐。还公开了使用这些化合物调节糖皮质激素受体活性的方法和包含这些化合物的药物组合物。

  公开号：

  US20110263494A1
• 作为产物：
  描述：

  [(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl](thiophen-2-yl)methanone 、 甲基溴化镁 以 四氢呋喃 、 乙醚 为溶剂， 以58 mg的产率得到(S)-1-[(5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl]-1-(thiophen-2-yl)ethanol
  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

• NONSTEROIDAL COMPOUNDS USEFUL AS MODULATORS OF GLUCOCORTICOID RECEPTOR AP-1 AND/OR NF-KAPPAB ACITIVITY AND USE THEREOF
  申请人：Dhar T.G. Murali

  公开号：US20110263494A1

  公开（公告）日：2011-10-27

  Disclosed are compounds of Formula (I) wherein: one of A and D is —N— and the other of A and D is —C—; or enantiomers, diastereomers, or pharmaceutically-acceptable salts thereof. Also disclosed are methods of using such compounds to modulate the function of glucocorticoid receptor activity and pharmaceutical compositions comprising such compounds.

  公开的是具有以下结构的化合物（I）：其中：A和D中的一个是—N—，另一个是—C—；或其对映体、非对映体异构体或药用盐。还公开了使用这些化合物调节糖皮质激素受体活性的方法和包含这些化合物的药物组合物。
• Nonsteroidal compounds useful as modulators of glucocorticoid receptor AP-1 and/or NF-kappab acitivity and use thereof
  申请人：Bristol-Myers Squibb Company

  公开号：US08309730B2

  公开（公告）日：2012-11-13

  Disclosed are compounds of Formula (I) wherein: one of A and D is —N— and the other of A and D is —C—; or enantiomers, diastereomers, or pharmaceutically-acceptable salts thereof. Also disclosed are methods of using such compounds to modulate the function of glucocorticoid receptor activity and pharmaceutical compositions comprising such compounds.

  本发明揭示了一种化合物，其化学式为（I），其中：A和D中的一个为—N—，而另一个为—C—；或其对映体、非对映体或药学上可接受的盐。本发明还揭示了使用这些化合物调节糖皮质激素受体活性的方法，以及包含这些化合物的药物组合物。
• NONSTEROIDAL COMPOUNDS USEFUL AS MODULATORS OF GLUCOCORTICOID RECEPTOR AP-1 AND/OR NF- KAPPA B ACTIVITY AND USE THEREOF
  申请人：Bristol-Myers Squibb Company

  公开号：EP2209780A2

  公开（公告）日：2010-07-28
• US8309730B2
  申请人：——

  公开号：US8309730B2

  公开（公告）日：2012-11-13
• [EN] NONSTEROIDAL COMPOUNDS USEFUL AS MODULATORS OF GLUCOCORTICOID RECEPTOR AP-1 AND/OR NF-?B ACTIVITY AND USE THEREOF<br/>[FR] COMPOSÉS NON STÉROÏDIENS UTILES EN TANT QUE MODULATEURS DE L'ACTIVITÉ AP-1 ET/OU NF-?B DU RÉCEPTEUR DES GLUCOCORTICOÏDES ET LEUR UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009058944A2

  公开（公告）日：2009-05-07

  Disclosed are compounds of Formula (I) wherein: one of A and D is -N- and the other of A and D is -C-; or enantiomers, diastereomers, or pharmaceutically-acceptable salts thereof. Also disclosed are methods of using such compounds to modulate the function of glucocorticoid receptor activity and pharmaceutical compositions comprising such compounds.