(R)-Benzo[b]thiophen-3-yl-[(4aR,5S)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-methanol | 614761-24-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-Benzo[b]thiophen-3-yl-[(4aR,5S)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-methanol
• 英文别名: (R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H,8H-cyclohexa[f]indazol-5-yl](1-benzothiophen-3-yl)methanol；(R)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-5,6,7,8-tetrahydro-4H-benzo[f]indazol-5-yl]-(1-benzothiophen-3-yl)methanol
• CAS: 614761-24-9
• 化学式: C₂₇H₂₅FN₂OS
• 分子量: 444.573
• InChiKey: GSBXDPQKEHNRQR-NPAAKHOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 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：

  (R)-Benzo[b]thiophen-3-yl-[(4aR,5S)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-methanol 在 sodium tetrahydroborate 、 N-甲基吲哚酮 、 四丙基高钌酸铵 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (S)-Benzo[b]thiophen-3-yl-[(4aR,5S)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-methanol
  参考文献：
  名称：

  Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy

  摘要：

  A series of novel ligands for the glucocorticoid receptor containing two heterocycles were synthesized. These compounds were investigated for a dissociative profile using transrepression and transactivation assays. Several compounds were tested in vivo and showed the ability to reduce inflammation in a mouse. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.02.009
• 作为产物：
  描述：

  3-lithiobenzothiophene 、 (4aR,5S)-1-(4-fluorophenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 (S)-Benzo[b]thiophen-3-yl-[(4aR,5S)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-methanol 、 (R)-Benzo[b]thiophen-3-yl-[(4aR,5S)-1-(4-fluoro-phenyl)-4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazol-5-yl]-methanol
  参考文献：
  名称：

  Novel heterocyclic glucocorticoids: in vitro profile and in vivo efficacy

  摘要：

  A series of novel ligands for the glucocorticoid receptor containing two heterocycles were synthesized. These compounds were investigated for a dissociative profile using transrepression and transactivation assays. Several compounds were tested in vivo and showed the ability to reduce inflammation in a mouse. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.02.009

文献信息

• 1H-benzo[F]indazol-5-YL derivatives as selective glucocorticoid receptor modulators
  申请人：Ali Amjad

  公开号：US20080076795A1

  公开（公告）日：2008-03-27

  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.
• METHODS FOR MODULATING INNATE LYMPHOID CELL ACTIVITY, ANTIBODY DRUG CONJUGATES AND USES IN THERAPY
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US20210024628A1

  公开（公告）日：2021-01-28

  The present invention relates to methods for modulating innate lymphoid cell activity, antibody drug conjugates and uses in therapy. The inventors showed in a model of murine cytomegalovirus infection, that glucocorticoid receptor expression in innate lymphoid cells plays an essential early role in regulating host protection against inflammation-induced tissue damage. Mechanistically, they demonstrated for the first time that endogenous glucocorticoids produced shortly after infection promote the expression of the immune checkpoint PD1 on the surface of natural killer cells. This glucocorticoid-PD1 pathway acts to limit the production of interferon-γ by NK cells. The modulation of the glucocorticoid-PD1 pathway in order to increase or decrease the activity of ILCs would permit to treat either cancers and infectious diseases or autoimmune and inflammatory diseases. In particular, the present invention relates to a method of modulating innate lymphoid cell activity which comprises modulating the activity of glucocorticoid receptor.
• US7282591B2
  申请人：——

  公开号：US7282591B2

  公开（公告）日：2007-10-16
• US7625937B2
  申请人：——

  公开号：US7625937B2

  公开（公告）日：2009-12-01
• US9126997B1
  申请人：——

  公开号：US9126997B1

  公开（公告）日：2015-09-08