(R)-(1-(4-fluorophenyl)-6-(m-tolylsulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone

• 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)-(1-(4-fluorophenyl)-6-(m-tolylsulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone
• 英文别名: ((4aR)-1-(4-fluorophenyl)-6-(m-tolylsulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone；[(4aR)-1-(4-fluorophenyl)-6-(3-methylphenyl)sulfonyl-4,5,7,8-tetrahydropyrazolo[3,4-g]isoquinolin-4a-yl]-pyridin-2-ylmethanone
• 化学式: C₂₉H₂₅FN₄O₃S
• 分子量: 528.607
• InChiKey: TUPIGZAWTJILKC-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  93.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-6-tert-butyl 4a-methyl 1-(4-fluorophenyl)-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-4a,6(4H)-dicarboxylate 在 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (R)-(1-(4-fluorophenyl)-6-(m-tolylsulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone
  参考文献：
  名称：

  Identification of the Clinical Candidate (R)-(1-(4-Fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134): A Selective Glucocorticoid Receptor (GR) Antagonist

  摘要：

  The nonselective glucocorticoid receptor (GR) antagonist mifepristone has been approved in the U.S. for the treatment of selected patients with Cushing's syndrome. While this drug is highly effective, lack, of selectivity for GR leads to unwanted side effects in Sonic patients. Optimization pf the previously described fused azadecalin series of selective GR antagonists l'ed to the identification of CORT125134, which is currently being eValuateddp a phase 2 clinical study in patients with Cushing's syndrome.

  DOI：

  10.1021/acs.jmedchem.7b00162

文献信息

• Heteroaryl-Ketone Fused Azadecalin Glucocorticoid Receptor Modulators
  申请人：Corcept Therapeutics, Inc.

  公开号：US20140038926A1

  公开（公告）日：2014-02-06

  The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了杂环基酮融合的氮杂十环化合物，以及使用这些化合物作为糖皮质激素受体调节剂的方法。
• HETEROARYL-KETONE FUSED AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Corcept Therapeutics, Inc.

  公开号：US20150080389A1

  公开（公告）日：2015-03-19

  The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了杂环酰酮融合的氮杂十二烷化合物以及使用这些化合物作为糖皮质激素受体调节剂的方法。
• Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
  申请人：Corcept Therapeutics, Inc.

  公开号：US10456392B2

  公开（公告）日：2019-10-29

  The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了杂芳基酮融合氮杂环丁烷化合物以及将这些化合物用作糖皮质激素受体调节剂的方法。
• 1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile
  作者：Hazel J. Hunt、Joseph K. Belanoff、Emily Golding、Benoit Gourdet、Timothy Phillips、Denise Swift、Jennifer Thomas、John F. Unitt、Iain Walters

  DOI：10.1016/j.bmcl.2015.10.097

  日期：2015.12

  We report the further optimization of our series 1H-pyrazolo[3,4-g]hexahydro-isoquinoline sulfonamides as GR antagonists. By incorporating a heteroaryl ketone group at the ring junction, we have obtained compounds with excellent functional GR antagonism. Optimization of the sulfonamide substituent has provided compounds with a very desirable overall profile, including minimal hERG activity, good bioavailability and in vivo efficacy. (C) 2015 Elsevier Ltd. All rights reserved.
• US8859774B2
  申请人：——

  公开号：US8859774B2

  公开（公告）日：2014-10-14