(7'Z,8a'S)-7'-(hydroxymethylene)-8a'-methyl-3',4',8',8a'-tetrahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(7'H)-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (7'Z,8a'S)-7'-(hydroxymethylene)-8a'-methyl-3',4',8',8a'-tetrahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(7'H)-one
• 英文别名: (8'aS)-8'a-methyl-3'-oxospiro[1,3-dioxolane-2,8'-2,5,6,7-tetrahydro-1H-naphthalene]-2'-carbaldehyde
• 化学式: C₁₄H₁₈O₄
• 分子量: 250.295
• InChiKey: MXJNQGFSGSQVLK-HQVZTVAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (7'Z,8a'S)-7'-(hydroxymethylene)-8a'-methyl-3',4',8',8a'-tetrahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(7'H)-one 在 盐酸 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 苯 为溶剂， 生成 (4aS)-1-(4-fluorophenyl)-4a-methyl-1,4,4a,6,7,8-hexahydro-5H-benzo[f]indazol-5-one
  参考文献：
  名称：

  Design and evaluation of novel nonsteroidal dissociating glucocorticoid receptor ligands

  摘要：

  A novel class of phenylpyrazole fused Wieland-Miescher ketone derivatives are high affinity, receptor specific, selective modulators of glucocorticoid receptor (GR) mediated transcription in vitro, dissociating transactivation, AP-1 repression, and NF-kappaB repression from each other. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.052
• 作为产物：
  描述：

  2-methyl-2-(3-oxobutyl)cyclohexane-1,3-dione 在 sodium hydride 、 对甲苯磺酸 、 L-脯氨酸 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 123.5h， 生成 (7'Z,8a'S)-7'-(hydroxymethylene)-8a'-methyl-3',4',8',8a'-tetrahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(7'H)-one
  参考文献：
  名称：

  Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion

  摘要：

  DOI：

  10.1021/acsmedchemlett.1c00379

文献信息

• Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion
  作者：Brandon J. Kennedy、Ashley M. Lato、Alexander R. Fisch、Susan J. Burke、Justin K. Kirkland、Carson W. Prevatte、Lee E. Dunlap、Russell T. Smith、Konstantinos D. Vogiatzis、J. Jason Collier、Shawn R. Campagna

  DOI：10.1021/acsmedchemlett.1c00379

  日期：2021.10.14
• Novel <i>N-</i>Arylpyrazolo[3,2-<i>c</i>]-Based Ligands for the Glucocorticoid Receptor:  Receptor Binding and in Vivo Activity
  作者：Amjad Ali、Christopher F. Thompson、James M. Balkovec、Donald W. Graham、Milton L. Hammond、Nazia Quraishi、James R. Tata、Monica Einstein、Lan Ge、Georgianna Harris、Terri M. Kelly、Paul Mazur、Shilpa Pandit、Joseph Santoro、Ayesha Sitlani、Chuanlin Wang、Joanne Williamson、Douglas K. Miller、Chris M. Thompson、Dennis M. Zaller、Michael J. Forrest、Ester Carballo-Jane、Silvi Luell

  DOI：10.1021/jm030585i

  日期：2004.5.1

  A novel series of selective ligands for the human glucocorticoid receptor (hGR) are described. Preliminary structure-activity relationships were focused on substitution at C-1 and indicated a preference for 3-, 4-, and 5-substituted aromatic and benzylic groups. The resulting analogues, e.g., 18 and 34, exhibited excellent affinity for hGR (IC50 1.9 nM and 2.8 PM, respectively) and an interesting partial agonist profile in functional assays of transactivation (tyrosine aminotransferase, TAT, and glutamine synthetase, GS) and transrepression (IL-6). The most potent compounds described in this study were the tertiary alcohol derivatives 21 and 25. These candidates showed highly efficacious IL-6 inhibition versus dexamethasone. The thiophenyl analogue 25 was evaluated in vivo in the mouse LPS challenge model and showed an ED50 = 4.0 mg/kg, compared to 0.5 mg/kg for prednisolone in the same assay.
• Design and evaluation of novel nonsteroidal dissociating glucocorticoid receptor ligands
  作者：Nilesh Shah、Thomas S. Scanlan

  DOI：10.1016/j.bmcl.2004.07.052

  日期：2004.10

  A novel class of phenylpyrazole fused Wieland-Miescher ketone derivatives are high affinity, receptor specific, selective modulators of glucocorticoid receptor (GR) mediated transcription in vitro, dissociating transactivation, AP-1 repression, and NF-kappaB repression from each other. (C) 2004 Elsevier Ltd. All rights reserved.
• Stereoisomers of an Aryl Pyrazole Glucocorticoid Receptor Agonist Scaffold Elicit Differing Anti-inflammatory Responses
  作者：Ashley M. Lato、Susan J. Burke、Maggie P. Ducote、Brandon J. Kennedy、J. Jason Collier、Shawn R. Campagna

  DOI：10.1021/acsmedchemlett.2c00299

  日期：2022.9.8