1,1,1-trifluoro-2-[(isoquinolin-5-ylamino)methyl]-3-(1-methyl-3,4-dihydro-2H-naphthalen-1-yl)propan-2-ol | 875796-87-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1,1,1-trifluoro-2-[(isoquinolin-5-ylamino)methyl]-3-(1-methyl-3,4-dihydro-2H-naphthalen-1-yl)propan-2-ol
• CAS: 875796-87-5
• 化学式: C₂₄H₂₅F₃N₂O
• 分子量: 414.471
• InChiKey: AEYUJQIHDRFOMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  45.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,1,1-trifluoro-3-(5-isoquinolinylimino)-2-[(1-methyl-1,2,3,4-tetrahydro-1-naphthalenyl)methyl]-2-propanol 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 反应 4.0h， 生成 1,1,1-trifluoro-2-[(isoquinolin-5-ylamino)methyl]-3-(1-methyl-3,4-dihydro-2H-naphthalen-1-yl)propan-2-ol
  参考文献：
  名称：

  Nonsteroidal Glucocorticoid Agonists: Tetrahydronaphthalenes with Alternative Steroidal A-Ring Mimetics Possessing Dissociated (Transrepression/Transactivation) Efficacy Selectivity

  摘要：

  The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NF kappa B glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). Quinolones, indoles, and C- and N-linked quinolines are some of the heterocycles that provide efficacy selectivity. For example, the isoquinoline 49D1E2 has NF kappa B agonism with pIC(50) of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the quinoline 55D1E1 has NF kappa B agonism with pIC(50) of 9.30 (101%) and reduced efficacy in MMTV agonism with pEC(50) of 8.02 (47%). A description of how a compound from each class is modeled in the active site of the receptor is given.

  DOI：

  10.1021/jm070778w

文献信息

• Tetrahydro-Naphthalene Derivatives as Glucocorticoid Receptor Modulators
  申请人：Edwards Christine

  公开号：US20070224130A1

  公开（公告）日：2007-09-27

  The present invention is directed to compounds of formula (I): wherein R represents a methyl or an ethyl group X represents N, C—H or C—CH 3 when X represents C—H or C—CH 3 , Y represents N when X represents N, Y represents C—H and physiologically functional derivatives thereof, pharmaceutical compositions comprising the compounds, the use of the compounds for the manufacture of medicaments particularly for the treatment of inflammatory and/or allergic conditions, processes for the preparation of the compounds, and chemical intermediates in the processes for the manufacture of the compounds.

  本发明涉及化合物公式(I)：其中R代表甲基或乙基基团，X代表N、C-H或C-CH3，当X代表C-H或C-CH3时，Y代表N，当X代表N时，Y代表C-H及其生理功能衍生物，包括该化合物的制药组合物，用于制造药物的化合物，特别是用于治疗炎症和/或过敏症状的药物，制备该化合物的过程以及制造该化合物的化学中间体。
• TETRAHYDRO-NAPHTHALENE DERIVATIVES AS GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1776119B1

  公开（公告）日：2012-01-18
• US7902224B2
  申请人：——

  公开号：US7902224B2

  公开（公告）日：2011-03-08
• Nonsteroidal Glucocorticoid Agonists: Tetrahydronaphthalenes with Alternative Steroidal A-Ring Mimetics Possessing Dissociated (Transrepression/Transactivation) Efficacy Selectivity
  作者：Keith Biggadike、Mohamed Boudjelal、Margaret Clackers、Diane M. Coe、Derek A. Demaine、George W. Hardy、Davina Humphreys、Graham G. A. Inglis、Michael J. Johnston、Haydn T. Jones、David House、Richard Loiseau、Deborah Needham、Philip A. Skone、Iain Uings、Gemma Veitch、Gordon G. Weingarten、Iain M. McLay、Simon J. F. Macdonald

  DOI：10.1021/jm070778w

  日期：2007.12.27

  The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NF kappa B glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). Quinolones, indoles, and C- and N-linked quinolines are some of the heterocycles that provide efficacy selectivity. For example, the isoquinoline 49D1E2 has NF kappa B agonism with pIC(50) of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the quinoline 55D1E1 has NF kappa B agonism with pIC(50) of 9.30 (101%) and reduced efficacy in MMTV agonism with pEC(50) of 8.02 (47%). A description of how a compound from each class is modeled in the active site of the receptor is given.