(4αS)-1-(4-fluorophenyl)-4α-methyl-4,4α,6,7-tetrahydrocyclopenta[f]indazol-5(1H)-one | 614763-02-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4αS)-1-(4-fluorophenyl)-4α-methyl-4,4α,6,7-tetrahydrocyclopenta[f]indazol-5(1H)-one
• 英文别名: (4aS)-1-(4-fluorophenyl)-4a-methyl-6,7-dihydro-4H-cyclopenta[f]indazol-5-one
• CAS: 614763-02-9
• 化学式: C₁₇H₁₅FN₂O
• 分子量: 282.317
• InChiKey: WYRPSGGSTOJZDH-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  (4αS)-1-(4-fluorophenyl)-4α-methyl-4,4α,6,7-tetrahydrocyclopenta[f]indazol-5(1H)-one 在 9-borabicyclo[3.3.1]nonane dimer 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-[(4aR,5S)-1-(4-fluorophenyl)-4a-methyl-1H,4H,4aH,5H,6H,7H-cyclopenta[f]indazol-5-yl](1-benzothiophen-3-yl)methanol
  参考文献：
  名称：

  Novel glucocorticoids containing a 6,5-bicyclic core fused to a pyrazole ring: Synthesis, in vitro profile, molecular modeling studies, and in vivo experiments

  摘要：

  Chemistry was developed to synthesize the title series of compounds. The ability of these novel ligands to bind to the glucocorticoid receptor was investigated. These compounds were also tested in a series of functional assays and some were found to display the profile of a dissociated glucocorticoid. The SAR of the 6,5-bicyclic series differed markedly from the previously reported 6,6-series. Molecular modeling studies were employed to understand the conformational differences between the two series of compounds, which may explain their divergent activity. Two compounds were profiled in vivo and shown to reduce inflammation in a mouse model. An active metabolite is suspected in one case. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.103
• 作为产物：
  描述：

  在 盐酸 、 sodium acetate 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 29.0h， 生成 (4αS)-1-(4-fluorophenyl)-4α-methyl-4,4α,6,7-tetrahydrocyclopenta[f]indazol-5(1H)-one
  参考文献：
  名称：

  Novel ketal ligands for the glucocorticoid receptor: in vitro and in vivo activity

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2005.03.027

文献信息

• [EN] HEXAHYDROCYCLOPENTYL[F]INDAZOLE PYRIDYL ETHANOLS AND DERIVATIVES THEREOF AS SELECTIVE GLUCOCORTICOID RECEPTOR MODULATORS<br/>[FR] HEXAHYDROCYCLOPENTYL[F]INDAZOLEPYRIDYL ÉTHANOLS ET LEUR DÉRIVÉS COMME MODULATEURS SÉLECTIFS DES RÉCEPTEURS AUX GLUCOCORTICOÏDES
  申请人：MERCK SHARP & DOHME

  公开号：WO2011053567A1

  公开（公告）日：2011-05-05

  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.

  本发明涵盖了化合物的公式(I)：或其药用可接受的盐或水合物，这些化合物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。药物组合物和使用方法也包括在内。
• 2-[1-PHENYL-5-HYDROXY OR METHOXY-4ALPHA-METHYL-HEXAHYDROCYCLOPENTA [f]INDAZOLE-5-YL]ETHYL PHENYL DERIVATIVES AS GLUCOCORTICOID RECEPTOR LIGANDS
  申请人：Bungard Christopher J.

  公开号：US20100311709A1

  公开（公告）日：2010-12-09

  The present invention is directed to 2-[ 1 -phenyl-5-hydroxy or methoxy-4alpha-methyl-hexahydrocyclopenta[f]indazol-5-yl]ethyl phenyl derivatives of formula I (I) as glucocorticoid receptor ligands useful for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included.

  本发明涉及公式I（I）的2-[1-苯基-5-羟基或甲氧基-4α-甲基-六氢环戊[f]吲唑-5-基]乙基苯基衍生物，作为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。还包括制药组合物和使用方法。
• 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
• SELECTIVE NON-STEROIDAL GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1599201B1

  公开（公告）日：2010-04-14
• SELECTIVE SPIROCYCLIC GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Merck & Co., Inc.

  公开号：EP1617806B1

  公开（公告）日：2009-11-04