(4aS)-1-(4-fluorophenyl)-4a-methyl-1,4,4a,6,7,8-hexahydro-5H-benzo[f]indazol-5-one | 614763-00-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (4aS)-1-(4-fluorophenyl)-4a-methyl-1,4,4a,6,7,8-hexahydro-5H-benzo[f]indazol-5-one
• 英文别名: 1-(4-fluorophenyl)-4a-methyl-1,4,4a,6,7,8-hexahydro-5H-benzo[f]indazol-5-one；(4aS)-1-(4-fluorophenyl)-4a-methyl-4,6,7,8-tetrahydrobenzo[f]indazol-5-one
• CAS: 614763-00-7
• 化学式: C₁₈H₁₇FN₂O
• 分子量: 296.344
• InChiKey: YGRBRGVIFJATCO-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4aS)-1-(4-fluorophenyl)-4a-methyl-1,4,4a,6,7,8-hexahydro-5H-benzo[f]indazol-5-one 在 盐酸 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 乙醚 、 水 、 甲苯 为溶剂， 反应 60.25h， 生成 (4-fluorophenyl)(1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl)methanol
  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
• 作为产物：
  描述：

  2-甲基-1,3-环己二酮 在 盐酸 、 sodium acetate 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 、 L-脯氨酸 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 131.0h， 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：

  Stereoisomers of an Aryl Pyrazole Glucocorticoid Receptor Agonist Scaffold Elicit Differing Anti-inflammatory Responses

  摘要：

  DOI：

  10.1021/acsmedchemlett.2c00299

文献信息

• Octahydro-2-h-naphtho[1,2-f]indole-4-carboxamide derivatives as selective glucocorticoid receptor modulators
  申请人：Ali Amjad

  公开号：US20050245588A1

  公开（公告）日：2005-11-03

  The present invention encompasses compounds of Formula I: or pharmaceutically acceptable salts or hydrates thereof, which are useful as selective glucocorticoid receptor ligands for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included.

  本发明涵盖以下化合物的公式I：或其药学上可接受的盐或水合物，它们可用作选择性糖皮质激素受体配体，用于治疗各种自身免疫和炎症性疾病或症状。还包括药物组成物和使用方法。
• 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.
• Novel ketal ligands for the glucocorticoid receptor: in vitro and in vivo activity
  作者：Cameron J. Smith、Amjad Ali、James M. Balkovec、Donald W. Graham、Milton L. Hammond、Gool F. Patel、Gregory P. Rouen、Scott K. Smith、James R. Tata、Monica Einstein、Lan Ge、Georgianna S. Harris、Theresa M. Kelly、Paul Mazur、Chris M. Thompson、Chuanlin F. Wang、Joanne M. Williamson、Douglas K. Miller、Shilpa Pandit、Joseph C. Santoro、Ayesha Sitlani、Ting-ting D. Yamin、Edward A. O’Neill、Dennis M. Zaller、Ester Carballo-Jane、Michael J. Forrest、Silvi Luell

  DOI：10.1016/j.bmcl.2005.03.027

  日期：2005.6

  A novel series of selective ligands for the human glucocorticoid receptor is described. Structure-activity studies focused on variation of B-ring size, ketal ring size, and ketal substitution. These analogs were found to be potent and selective ligands for GR and have partial agonist profiles in functional assays for transactivation (TAT, GS) and transrepression (IL-6). Of these compounds, 27, 28, and 35 were evaluated further in a mouse LPS-induced TNF-alpha secretion model. Compound 28 had an ED50 Of 14.1 mg/kg compared with 0.5 mg/kg for prednisolone in the same assay. (c) 2005 Elsevier Ltd. All rights reserved.
• 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.
• 1H-BENZO(F)INDAZOL-5-YL DERIVATIVES AS SELECTIVE GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1496892B1

  公开（公告）日：2011-01-26