(1S,7aS)-1-hydroxy-7a-methyl-1-[(trimethylsilyl)ethynyl]-1,2,3,6,7,7a-hexahydro-5H-inden-5-one | 1021539-23-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,7aS)-1-hydroxy-7a-methyl-1-[(trimethylsilyl)ethynyl]-1,2,3,6,7,7a-hexahydro-5H-inden-5-one
• 英文别名: (1S,7αS)-1-hydroxy-7α-methyl-1-[(trimethylsilyl)ethynyl]-1,2,3,6,7,7α-hexahydro-5H-inden-5-one；(1S,7α'S)-1-hydroxy-7α'-methyl-1-[(trimethylsilyl)ethynyl]-1,2,3,6,7,7α-hexahydro-5H-indene-5-one；(1S,7aS)-1-hydroxy-7a-methyl-1-(2-trimethylsilylethynyl)-2,3,6,7-tetrahydroinden-5-one
• CAS: 1021539-23-0
• 化学式: C₁₅H₂₂O₂Si
• 分子量: 262.424
• InChiKey: PKPRCVQBJSNWMW-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,7aS)-1-hydroxy-7a-methyl-1-[(trimethylsilyl)ethynyl]-1,2,3,6,7,7a-hexahydro-5H-inden-5-one 在 甲醇 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 反应 7.75h， 生成 (3R,3aS)-3-ethynyl-3-hydroxy-3a-methyl-6-oxo-2,3,3a,4,5,6-hexahydro-1H-indene-5-carbaldehyde
  参考文献：
  名称：

  Discovery of selective glucocorticoid receptor modulator MK-5932

  摘要：

  A series of partial agonists of the Glucocorticoid Receptor were prepared targeting reduced transactivation activity, while maintaining significant transrepression activity. Incorporation of an ortho-aryl amide produced compounds with the desired in vitro profile. Bioreactors consisting of Suspension cultures of Sf21 cells co expressing a CYP3A4 and NADPH-cytochrome P450 oxireductase were used to prepare the major metabolites of these compounds and revealed that oxidative N-dealkylation provided a pathway for formation of metabolites that were more agonistic than the parent partial agonists. Oxidative N-dealkylation was blocked in a new series of compounds, however oxidation alone was capable of producing full agonist metabolites. Incorporation of an ortho-primary amide and utilization of fluorine to modulate agonism afforded partial agonist MK-5932. Synthesis of the major metabolites of MK-5932 using bioreactor technology revealed that no significant GR-active metabolites were formed. Orally administered MK-5932 displayed anti-inflammatory efficacy in a Rat Oxazolone-induced chronic dermatitis model, while sparing plasma insulin. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.054
• 作为产物：
  描述：

  (S)-(+)-2,3,7,7A-四氢-7A-甲基-1H-茚-1,5(6H)-二酮 、 三甲基乙炔基硅 在 正丁基锂 、 potassium dihydrogenphosphate 、 水 作用下， 以 四氢呋喃 、 hexanes 为溶剂， 反应 1.0h， 以80%的产率得到(1S,7aS)-1-hydroxy-7a-methyl-1-[(trimethylsilyl)ethynyl]-1,2,3,6,7,7a-hexahydro-5H-inden-5-one
  参考文献：
  名称：

  [EN] PROCESS FOR MAKING GLUCOCORTICOID RECEPTOR LIGANDS
  [FR] PROCÉDÉ DE PRÉPARATION DE LIGANDS DU RÉCEPTEUR DES GLUCOCORTICOÏDES

  摘要：

  这项发明涵盖了一种制备2-[1-苯基-5-羟基-4α-甲基-六氢环戊基吲唑-5-基]乙基苯衍生物的过程，这些衍生物是糖皮质激素受体配体，用于治疗炎症和免疫性疾病。

  公开号：

  WO2009054925A1

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。
• WO2008/51532
  申请人：——

  公开号：——

  公开（公告）日：——